text:
Lamivudine/Zidovudine Mylan 150 mg/300 mg Film-coated Tablets
Mylan contact details
Each film-coated tablet contains 150 mg lamivudine and 300 mg zidovudine
White to off-white, capsule shaped, biconvex film-coated tablets, debossed with "M" on the left of the scoreline and "103" on the right, on one side of the tablet, and scored on the other side.
The tablet can be divided into equal doses.
Lamivudine/Zidovudine Mylan is indicated in antiretroviral combination therapy for the treatment of Human Immunodeficiency Virus (HIV) infection (see section 4.2).
Therapy should be initiated by a physician experienced in the management of HIV infection.
Adults and adolescents weighing at least 30 kg
The recommended dose of Lamivudine/Zidovudine Mylan is one tablet twice daily.
Children weighing between 21 kg and 30 kg
The recommended oral dose of Lamivudine/Zidovudine Mylan is one-half tablet taken in the morning and one whole tablet taken in the evening.
Children weighing from 14 kg to 21 kg
The recommended oral dose of Lamivudine/Zidovudine Mylan is one-half tablet taken twice daily.
The dosing regimen for paediatric patients weighing 14-30 kg is based primarily on pharmacokinetic modelling and supported by data from clinical studies using the individual components lamivudine and zidovudine. A pharmacokinetic overexposure of zidovudine can occur, therefore close safety monitoring is warranted in these patients. If gastrointestinal intolerance occurs in patients weighing 21-30 kg, an alternative dosing schedule with one-half tablet taken thrice daily can be applied in attempt to improve tolerability.
Lamivudine/Zidovudine Mylan tablets should not be used for children weighing less than 14 kg, since doses cannot be appropriately adjusted for the weight of the child. In these patients, lamivudine and zidovudine should be taken as separate formulations according to the prescribed dosing recommendations for these products. For these patients and for patients who are unable to swallow tablets, oral solutions of lamivudine and zidovudine are available.
For situations where discontinuation of therapy with one of the active substances of Lamivudine/Zidovudine Mylan, or dose reduction is necessary, separate preparations of lamivudine and zidovudine are available in tablets/capsules and oral solution.
Lamivudine and zidovudine concentrations are increased in patients with renal impairment due to decreased clearance. Therefore, as dosage adjustment of these may be necessary, it is recommended that separate preparations of lamivudine and zidovudine be administered to patients with reduced renal function (creatinine clearance ≤ 50 ml/min). Physicians should refer to the individual prescribing information for these medicinal products.
Limited data in patients with cirrhosis suggest that accumulation of zidovudine may occur in patients with hepatic impairment because of decreased glucuronidation. Data obtained in patients with moderate to severe hepatic impairment show that lamivudine pharmacokinetics are not significantly affected by hepatic dysfunction. However, as dosage adjustments for zidovudine may be necessary, it is recommended that separate preparations of lamivudine and zidovudine be administered to patients with severe hepatic impairment. Physicians should refer to the individual prescribing information for these medicinal products.
Haematological adverse reactions
Dosage adjustment of zidovudine may be necessary if the haemoglobin level falls below 9 g/dl or 5.59 mmol/l or the neutrophil count falls below 1.0 x 109/l (see sections 4.3 and 4.4). As dosage adjustment of Lamivudine/Zidovudine Mylan is not possible, separate preparations of zidovudine and lamivudine should be used. Physicians should refer to the individual prescribing information for these medicinal products.
No specific data are available, however special care is advised in this age group due to age associated changes such as the decrease in renal function and alteration of haematological parameters.
For oral use.
Lamivudine/Zidovudine Mylan may be administered with or without food.
To ensure administration of the entire dose, the tablet(s) should ideally be swallowed without crushing. For patients who are unable to swallow tablets, these may be crushed and added to a small amount of semi-solid food or liquid, all of which should be consumed immediately (see section 5.2).
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
Zidovudine is contraindicated in patients with abnormally low neutrophil counts (<0.75 x 109/l), or abnormally low haemoglobin levels (<7.5 g/dl or 4.65 mmol/l). Lamivudine/Zidovudine Mylan is therefore contraindicated in these patients (see section 4.4).
While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission should be taken in accordance with national guidelines.
The special warnings and precautions relevant to both lamivudine and zidovudine are included in this section. There are no additional precautions and warnings relevant to the combination Lamivudine/Zidovudine Mylan.
It is recommended that separate preparations of lamivudine and zidovudine should be administered in cases where dosage adjustment is necessary (see section 4.2). In these cases the physician should refer to the individual prescribing information for these medicinal products.
The concomitant use of stavudine with zidovudine should be avoided (see section 4.5).
Patients receiving Lamivudine/Zidovudine Mylan or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV infection. Therefore patients should remain under close clinical observation by physicians experienced in the treatment of HIV infection.
Anaemia, neutropenia and leucopenia (usually secondary to neutropenia) can be expected to occur in patients receiving zidovudine. These occurred more frequently at higher zidovudine dosages (1200-1500 mg/day) and in patients with poor bone marrow reserve prior to treatment, particularly with advanced HIV disease. Haematological parameters should therefore be carefully monitored (see section 4.3) in patients receiving Lamivudine/Zidovudine Mylan. These haematological effects are not usually observed before four to six weeks therapy. For patients with advanced symptomatic HIV disease, it is generally recommended that blood tests are performed at least every two weeks for the first three months of therapy and at least monthly thereafter.
In patients with early HIV disease haematological adverse reactions are infrequent. Depending on the overall condition of the patient, blood tests may be performed less often, for example every one to three months. Additionally dosage adjustment of zidovudine may be required if severe anaemia or myelosuppression occurs during treatment with Lamivudine/Zidovudine Mylan, or in patients with pre-existing bone marrow compromise e.g. haemoglobin <9 g/dl (5.59 mmol/l) or neutrophil count <1.0 x 109/l (see section 4.2). As dosage adjustment of Lamivudine/Zidovudine Mylan is not possible, separate preparations of zidovudine and lamivudine should be used. Physicians should refer to the individual prescribing information for these medicinal products.
Cases of pancreatitis have occurred rarely in patients treated with lamivudine and zidovudine. However it is not clear whether these cases were due to the antiretroviral treatment or to the underlying HIV disease. Treatment with Lamivudine/Zidovudine Mylan should be stopped immediately if clinical signs, symptoms or laboratory abnormalities suggestive of pancreatitis occur.
Lactic acidosis: lactic acidosis usually associated with hepatomegaly and hepatic steatosis has been reported with the use of nucleoside analogues. Early symptoms (symptomatic hyperlactatemia) include benign digestive symptoms (nausea, vomiting and abdominal pain) non-specific malaise, loss of appetite, weight loss, respiratory symptoms (rapid and/or deep breathing) or neurological symptoms (including motor weakness).
Lactic acidosis has a high mortality and may be associated with pancreatitis, liver failure, or renal failure.
Lactic acidosis generally occurred after a few or several months of treatment.
Treatment with nucleoside analogues should be discontinued if there is symptomatic hyperlactatemia and metabolic/lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels.
Caution should be exercised when administering nucleoside analogues to any patient (particularly obese women) with hepatomegaly, hepatitis or other known risk factors for liver disease and hepatic steatosis (including certain medicinal products and alcohol). Patients co-infected with hepatitis C and treated with alpha interferon and ribavirin may constitute a special risk.
Patients at increased risk should be followed closely.
Mitochondrial dysfunction following exposure in utero
Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine. There have been reports of mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally to nucleoside analogues; these have predominantly concerned treatment with regimens containing zidovudine. The main adverse reactions reported are haematological disorders (anaemia, neutropenia) and metabolic disorders (hyperlactatemia, hyperlipasemia). These reactions have often been transitory. Late-onset neurological disorders have been reported rarely (hypertonia, convulsion, abnormal behaviour). Whether such neurological disorders are transient or permanent is currently unknown. These findings should be considered for any child exposed in utero to nucleoside and nucleotide analogues, who presents with severe clinical findings of unknown etiology, particularly neurologic findings. These findings do not affect current national recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of HIV.
Lipoatrophy
Treatment with zidovudine has been associated with loss of subcutaneous fat, which has been linked to mitochondrial toxicity. The incidence and severity of lipoatrophy are related to cumulative exposure. This fat loss, which is most evident in the face, limbs and buttocks, may not be reversible when switching to a zidovudine-free regimen. Patients should be regularly assessed for signs of lipoatrophy during therapy with zidovudine and zidovudine-containing products. Therapy should be switched to an alternative regimen if there is suspicion of lipoatrophy development.
Weight and metabolic parameters
An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy. Such changes may in part be linked to disease control and life style. For lipids, there is in some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating this to any particular treatment. For monitoring of blood lipids and glucose reference is made to established HIV treatment guidelines. Lipid disorders should be managed as clinically appropriate.
Immune Reactivation Syndrome
In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, such reactions have been observed within the first few weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterium infections, and Pneumocystis jirovecii pneumonia (often referred to as PCP). Any inflammatory symptoms should be evaluated and treatment instituted when necessary. Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.
If lamivudine is being used concomitantly for the treatment of HIV and HBV, additional information relating to the use of lamivudine in the treatment of hepatitis B infection is available in the corresponding SmPC.
The safety and efficacy of zidovudine has not been established in patients with significant underlying liver disorders.
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk of severe and potentially fatal hepatic adverse events. In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these medicinal products.
If Lamivudine/Zidovudine Mylan is discontinued in patients co-infected with hepatitis B virus, periodic monitoring of both liver function tests and markers of HBV replication for 4 months is recommended, as withdrawal of lamivudine may result in an acute exacerbation of hepatitis.
Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities during combination antiretroviral therapy, and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Co-infection with hepatitis C virus
The concomitant use of ribavirin with zidovudine is not recommended due to an increased risk of anaemia (see section 4.5).
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/or long-term exposure to combination antiretroviral therapy (CART). Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Lamivudine/Zidovudine Mylan should not be taken with any other medicinal products containing lamivudine or medicinal products containing emtricitabine.
The combination of lamivudine with cladribine is not recommended (see section 4.5).
Lamivudine/Zidovudine Mylan contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.
Lamivudine/Zidovudine Mylan contains lamivudine and zidovudine, therefore any interactions identified for these individually are relevant to Lamivudine/Zidovudine Mylan. Clinical studies have shown that there are no clinically significant interactions between lamivudine and zidovudine.
Zidovudine is primarily metabolised by UGT enzymes; co-administration of inducers or inhibitors of UGT enzymes could alter zidovudine exposure. Lamivudine is cleared renally. Active renal secretion of lamivudine in the urine is mediated through organic cation transporters (OCTs); co-administration of lamivudine with OCT inhibitors or nephrotoxic drugs may increase lamivudine exposure.
Lamivudine and zidovudine are not significantly metabolised by cytochrome P450 enzymes (such as CYP 3A4, CYP 2C9 or CYP 2D6) nor do they inhibit or induce this enzyme system. Therefore, there is little potential for interactions with antiretroviral protease inhibitors, non-nucleosides and other medicinal products metabolised by major P450 enzymes.
Interaction studies have only been performed in adults. The list below should not be considered exhaustive but is representative of the classes studied.
Medicinal products by Therapeutic Area
Geometric mean change (%)
(Possible mechanism)
Recommendations concerning co-administration
Antiretroviral Medicinal Products
Didanosine/Lamivudine
Interaction not studied.
No dosage adjustment necessary.
Didanosine /Zidovudine
Stavudine/Lamivudine
Combination not recommended.
Stavudine/Zidovudine
In vitro antagonism of anti-HIV activity between stavudine and zidovudine could result in decreased efficacy of both drugs.
Anti-Infective Products
Atovaquone/Lamivudine
As only limited data available the clinical significance is unknown.
Atovaquone/Zidovudine (750 mg twice daily with food/200 mg thrice daily)
Zidovudine AUC ↑33%
Atovaquone AUC ↔
Clarithromycin/Lamivudine
Separate administration of Lamivudine/Zidovudine Mylan and clarithromycin by at least 2 hours
Clarithromycin/Zidovudine (500 mg twice daily/100 mg every 4 hours)
Zidovudine AUC ↓12%
Trimethoprim/sulfamethoxazole (Co-trimoxazole)/Lamivudine (160mg/800mg once daily for 5 days/300mg single dose)
Lamivudine: AUC ↑40%
Trimethoprim: AUC ↔
Sulfamethoxazole: AUC ↔
(organic cation transporter inhibition)
No Lamivudine/Zidovudine Mylan dosage adjustment necessary, unless patient has renal impairment (See Section 4.2).
When concomitant administration with co-trimoxazole is warranted, patients should be monitored clinically. High doses of trimethoprim/ sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis have not been studied and should be avoided.
Trimethoprim/sulfamethoxazole (Co-trimoxazole)/Zidovudine
Fluconazole/Lamivudine
As only limited data are available the clinical significance is not known. Monitor for signs of zidovudine toxicity (see section 4.8).
Fluconazole/Zidovudine (400 mg once daily/200 mg thrice daily)
Zidovudine AUC ↑74% (UGT inhibition)
Antimycobacterials
Rifampicin/Lamivudine
Insufficient data to recommend dosage adjustment.
Rifampicin/Zidovudine (600mg once daily/200 mg thrice daily)
Zidovudine AUC ↓48% (UGT induction)
Phenobarbital/Lamivudine
Phenobarbital/Zidovudine
Interaction not studied. Potential to slightly decrease zidovudine plasma concentrations through UGT induction.
Phenytoin/Lamivudine
Monitor phenytoin concentrations.
Phenytoin/Zidovudine
Phenytoin AUC ↑↓
Valproic acid/Lamivudine
Valproic acid/Zidovudine (250 mg or 500 mg thrice daily/100 mg thrice daily)
Antihistamines (Histamine H1 Receptor Antagonists)
Ranitidine/Lamivudine
Interaction not studied. Clinically significant interaction unlikely. Ranitidine eliminated only in part by renal organic cation transport system.
Ranitidine/Zidovudine
Interaction not studied
Cimetidine/Lamivudine
Interaction not studied. Clinically significant interaction unlikely. Cimetidine eliminated only in part by renal organic cation transport system.
Cimetidine/Zidovudine
Cytotoxics
Cladribine/Lamivudine
In vitro lamivudine inhibits the intracellular phosphorylation of cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical setting.
Some clinical findings also support a possible interaction between lamivudine and cladribine.
Therefore the concomitant use of lamivudine with cladribine is not recommended (see section 4.4)
Methadone/Lamivudine
Methadone dosage adjustment unlikely in majority of patients; occasionally methadone re-titration may be required.
Methadone/Zidovudine (30 to 90 mg once daily/200 mg every 4 hours)
Zidovudine AUC ↑43% Methadone AUC ↔
Uricosuric
Probenecid/Lamivudine
Probenecid/Zidovudine (500 mg four times daily/2mg/kg thrice daily)
Zidovudine AUC ↑106% (UGT inhibition)
Sorbitol solution (3.2 g, 10.2 g, 13.4 g)/ Lamivudine
Single dose lamivudine oral solution 300 mg
Lamivudine:
AUC ↓ 14%; 32%; 36%
Cmax ↓ 28%; 52%, 55%.
When possible, avoid chronic coadministration of lamivudine/zidovudine with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (e.g. xylitol, mannitol, lactitol, maltitol). Consider more frequent monitoring of HIV-1 viral load when chronic coadministration cannot be avoided.
Abbreviations: ↑ = Increase; ↓ =decrease; ↔= no significant change; AUC=area under the concentration versus time curve; Cmax=maximum observed concentration; CL/F=apparent oral clearance
Exacerbation of anaemia due to ribavirin has been reported when zidovudine is part of the regimen used to treat HIV although the exact mechanism remains to be elucidated. The concomitant use of ribavirin with zidovudine is not recommended due to an increased risk of anaemia (see section 4.4).
Consideration should be given to replacing zidovudine in a combination ART regimen if this is already established. This would be particularly important in patients with a known history of zidovudine induced anaemia.
Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products (e.g. systemic pentamidine, dapsone, pyrimethamine, co-trimoxazole, amphotericin, flucytosine, ganciclovir, interferon, vincristine, vinblastine and doxorubicin) may also increase the risk of adverse reactions to zidovudine. If concomitant therapy with Lamivudine/Zidovudine Mylan and any of these medicinal products is necessary then extra care should be taken in monitoring renal function and haematological parameters and, if required, the dosage of one or more agents should be reduced.
Limited data from clinical trials do not indicate a significantly increased risk of adverse reactions to zidovudine with co-trimoxazole (see interaction information above relating to lamivudine and co-trimoxazole), aerosolised pentamidine, pyrimethamine and acyclovir at doses used in prophylaxis.
As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, the animal data as well as the clinical experience in pregnant women should be taken into account. In the present case, the use in pregnant women of zidovudine, with subsequent treatment of the newborn infants, has been shown to reduce the rate of maternal-foetal transmission of HIV. A large amount of data on pregnant women taking lamivudine or zidovudine indicate no malformative toxicity (more than 3000 outcomes from first trimester exposure each, of which over 2000 outcomes involved exposure to both lamivudine and zidovudine). The malformative risk is unlikely in humans based on the mentioned large amount of data
The active ingredients of Lamivudine/Zidovudine Mylan may inhibit cellular DNA replication and zidovudine has been shown to be transplacental carcinogen in one animal study (see section 5.3). The clinical relevance of these findings is unknown.
For patients co-infected with hepatitis who are being treated with lamivudine containing medicinal products such as Lamivudine/Zidovudine Mylan and subsequently become pregnant, consideration should be given to the possibility of a recurrence of hepatitis on discontinuation of lamivudine.
Mitochondrial dysfunction: nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable degree of mitochondrial damage. There have been reports of mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally to nucleoside analogues (see section 4.4).
Both lamivudine and zidovudine are excreted in breast milk at similar concentrations to those found in serum.
Based on more than 200 mother/child pairs treated for HIV, serum concentrations of lamivudine in breastfed infants of mothers treated for HIV are very low (< 4% of maternal serum concentrations) and progressively decrease to undetectable levels when breastfed infants reach 24 weeks of age. There are no data available on the safety of lamivudine when administered to babies less than three months old.
After administration of a single dose of 200 mg zidovudine to HIV-infected women, the mean concentration of zidovudine was similar in human milk and serum.
It is recommended that mothers infected by HIV do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.
Neither zidovudine nor lamivudine have shown evidence of impairment of fertility in studies in male and female rats. There are no data on their effect on human female fertility.
In men zidovudine has not been shown to affect sperm count, morphology or motility.
Adverse reactions have been reported during therapy for HIV disease with lamivudine and zidovudine separately or in combination. For many of these events, it is unclear whether they are related to lamivudine, zidovudine, the wide range of medicinal products used in the management of HIV disease, or as a result of the underlying disease process.
As Lamivudine/Zidovudine Mylan contains lamivudine and zidovudine, the type and severity of adverse reactions associated with each of the compounds may be expected. There is no evidence of added toxicity following concurrent administration of the two compounds.
Cases of lactic acidosis, sometimes fatal, usually associated with severe hepatomegaly and hepatic steatosis, have been reported with the use of nucleoside analogues (see section 4.4).
Treatment with zidovudine has been associated with loss of subcutaneous fat which is most evident in the face, limbs and buttocks. Patients receiving Lamivudine/Zidovudine Mylan should be frequently examined and questioned for signs of lipoatrophy. When such development is found, treatment with lamivudine/zidovudine should not be continued (see section 4.4).
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see section 4.4).
In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment (see section 4.4).
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART). The frequency of this is unknown (see section 4.4).
The adverse reactions considered at least possibly related to the treatment are listed below by body system, organ class and absolute frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Blood and lymphatic systems disorders
Uncommon: Neutropenia and anaemia (both occasionally severe), thrombocytopenia
Very rare: Pure red cell aplasia
Very rare: Lactic acidosis
Common: Headache, insomnia
Very rare: Peripheral neuropathy (or paraesthesiae)
Common: Cough, nasal symptoms
Common: Nausea, vomiting, abdominal pain or cramps, diarrhoea
Rare: Pancreatitis, rises in serum amylase
Uncommon: Transient rises in liver enzymes (AST, ALT)
Rare: Hepatitis
Common: Rash, alopecia
Rare: angioedema
Common: Arthralgia, muscle disorders
Rare: Rhabdomyolysis
Common: Fatigue, malaise, fever
Zidovudine:
The adverse reactions profile appears similar for adults and adolescents. The most serious adverse reactions include anaemia (which may require transfusions), neutropenia and leucopenia. These occurred more frequently at higher dosages (1200-1500 mg/day) and in patients with advanced HIV disease (especially when there is poor bone marrow reserve prior to treatment), and particularly in patients with CD4 cell counts less than 100/mm3 (see section 4.4).
The incidence of neutropenia was also increased in those patients whose neutrophil counts, haemoglobin levels and serum vitamin B12 levels were low at the start of zidovudine therapy.
The adverse reactions considered at least possibly related to the treatment are listed below by body system, organ class and absolute frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Common: Anaemia, neutropenia and leucopenia
Uncommon: Thrombocytoopenia and pancytopenia (with marrow hypoplasia)
Rare: Pure red cell aplasia
Very rare: Aplastic anaemia
Rare: Lactic acidosis in the absence of hypoxaemia, anorexia
Rare: Anxiety and depression
Very common: Headache
Common: Dizziness
Rare: Insomnia, paraesthesiae, somnolence, loss of mental acuity, convulsions
Rare: Cardiomyopathy
Uncommon: Dyspnoea
Rare: Cough
Very common: Nausea
Common: Vomiting, abdominal pain and diarrhoea
Uncommon: Flatulence
Rare: Oral mucosa pigmentation, taste perversion and dyspepsia. Pancreatitis
Common: Raised blood levels of liver enzymes and bilirubin
Rare: Liver disorders such as severe hepatomegaly with steatosis
Uncommon: Rash and pruritus
Rare: Nail and skin pigmentation, urticaria and sweating
Common: Myalgia
Uncommon: Myopathy
Rare: Urinary frequency
Rare: Gynaecomastia
Common: Malaise
Uncommon: Fever, generalised pain and asthenia
Rare: Chills, chest pain and influenza-like syndrome
The available data from both placebo-controlled and open-label studies indicate that the incidence of nausea and other frequently reported clinical adverse events consistently decreases over time during the first few weeks of therapy with zidovudine.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
There is limited experience of overdosage with Lamivudine/Zidovudine.
No specific symptoms or signs have been identified following acute overdose with zidovudine or lamivudine apart from those listed as undesirable effects. No fatalities occurred, and all patients recovered.
If overdosage occurs the patient should be monitored for evidence of toxicity (see section 4.8), and standard supportive treatment applied as necessary. Since lamivudine is dialysable, continuous haemodialysis could be used in the treatment of overdosage, although this has not been studied. Haemodialysis and peritoneal dialysis appear to have a limited effect on elimination of zidovudine, but enhance the elimination of the glucuronide metabolite. For more details physicians should refer to the individual prescribing information for lamivudine and zidovudine.
Pharmacotherapeutic group: Antivirals for treatment of HIV infections, combinations, ATC Code: J05AR01
Lamivudine and zidovudine are nucleoside analogues which have activity against HIV. Additionally, lamivudine has activity against hepatitis B virus (HBV). Both medicinal products are metabolised intracellularly to their active moieties, lamivudine 5'-triphosphate (TP) and zidovudine 5'-TP respectively. Their main modes of action are as chain terminators of viral reverse transcription. Lamivudine-TP and zidovudine-TP have selective inhibitory activity against HIV-1 and HIV-2 replication in vitro; lamivudine is also active against zidovudine-resistant clinical isolates of HIV. No antagonistic effects in vitro were seen with lamivudine and other antiretrovirals (tested agents: abacavir, didanosine and nevirapine). No antagonistic effects in vitro were seen with zidovudine and other antiretrovirals (tested agents: abacavir, didanosine and interferon alpha).
HIV-1 resistance to lamivudine involves the development of a M184V amino acid change close to the active site of the viral reverse transcriptase (RT). This variant arises both in vitro and in HIV-1 infected patients treated with lamivudine-containing antiretroviral therapy. M184V mutants display greatly reduced susceptibility to lamivudine and show diminished viral replicative capacity in vitro. In vitro studies indicate that zidovudine-resistant virus isolates can become zidovudine sensitive when they simultaneously acquire resistance to lamivudine. The clinical relevance of such findings remains, however, not well defined.
In vitro data tend to suggest that the continuation of lamivudine in anti-retroviral regimen despite the development of M184V might provide residual anti-retroviral activity (likely through impaired viral fitness). The clinical relevance of these findings is not established. Indeed, the available clinical data are very limited and preclude any reliable conclusion in the field. In any case, initiation of susceptible NRTI's should always be preferred to maintenance of lamivudine therapy. Therefore, maintaining lamivudine therapy despite emergence of M184V mutation should only be considered in cases where no other active NRTIs are available.
Cross-resistance conferred by the M184V RT is limited within the nucleoside inhibitor class of antiretroviral agents. Zidovudine and stavudine maintain their antiretroviral activities against lamivudine-resistant HIV-1. Abacavir maintains its antiretroviral activities against lamivudine-resistant HIV-1 harbouring only the M184V mutation. The M184V RT mutant shows a <4-fold decrease in susceptibility to didanosine; the clinical significance of these findings is unknown. In vitro susceptibility testing has not been standardised and results may vary according to methodological factors.
Lamivudine demonstrates low cytotoxicity to peripheral blood lymphocytes, to established lymphocyte and monocyte-macrophage cell lines, and to a variety of bone marrow progenitor cells in vitro. Resistance to thymidine analogues (of which zidovudine is one) is well characterised and is conferred by the stepwise accumulation of up to six specific mutations in the HIV reverse transcriptase at codons 41, 67, 70, 210, 215 and 219. Viruses acquire phenotypic resistance to thymidine analogues through the combination of mutations at codons 41 and 215 or by the accumulation of at least four of the six mutations. These thymidine analogue mutations alone do not cause high-level cross-resistance to any of the other nucleosides, allowing for the subsequent use of any of the other approved reverse transcriptase inhibitors.
Two patterns of multi-drug resistance mutations, the first characterised by mutations in the HIV reverse transcriptase at codons 62, 75, 77, 116 and 151, and the second involving a T69S mutation plus a 6-base pair insert at the same position, result in phenotypic resistance to AZT as well as to the other approved NRTIs. Either of these two patterns of multinucleoside resistance mutations severely limits future therapeutic options.
In clinical trials, lamivudine in combination with zidovudine has been shown to reduce HIV-1 viral load and increase CD4 cell count. Clinical end-point data indicate that lamivudine in combination with zidovudine, results in a significant reduction in the risk of disease progression and mortality.
Lamivudine and zidovudine have been widely used as components of antiretroviral combination therapy with other antiretroviral agents of the same class (NRTIs) or different classes (PIs, non-nucleoside reverse transcriptase inhibitors).
Multiple drug antiretroviral therapy containing lamivudine has been shown to be effective in antiretrovirally-naive patients as well as in patients presenting with viruses containing the M184V mutations.
Evidence from clinical studies shows that lamivudine plus zidovudine delays the emergence of zidovudine resistant isolates in individuals with no prior antiretroviral therapy. Subjects receiving lamivudine and zidovudine with or without additional concomitant antiretroviral therapies and who already present with the M184V mutant virus also experience a delay in the onset of mutations that confer resistance to zidovudine and stavudine (Thymidine Analogue Mutations; TAMs).
The relationship between in vitro susceptibility of HIV to lamivudine and zidovudine and clinical response to lamivudine/zidovudine containing therapy remains under investigation.
Lamivudine at a dose of 100 mg once daily has also been shown to be effective for the treatment of adult patients with chronic HBV infection (for details of clinical studies, see the prescribing information in the corresponding SmPC). However, for the treatment of HIV infection only a 300 mg daily dose of lamivudine (in combination with other antiretroviral agents) has been shown to be efficacious.
Lamivudine has not been specifically investigated in HIV patients co-infected with HBV.
Lamivudine and zidovudine are well absorbed from the gastrointestinal tract. The bioavailability of oral lamivudine in adults is normally between 80–85% and for zidovudine 60–70%.
A bioequivalence study compared lamivudine/zidovudine combination with lamivudine 150 mg and zidovudine 300 mg tablets taken together. The effect of food on the rate and extent of absorption was also studied. Lamivudine/Zidovudine was shown to be bioequivalent to lamivudine 150 mg and zidovudine 300 mg given as separate tablets, when administered to fasting subjects.
Following single dose lamivudine/zidovudine combination administration in healthy volunteers, mean (CV) lamivudine and zidovudine Cmax values were 1.6 µg/ml (32%) and 2.0 µg/ml (40%), respectively, and the corresponding values for AUC were 6.1 µg h/ml (20%) and 2.4 µg h/ml (29%), respectively. The median (range) lamivudine and zidovudine tmax values were 0.75 (0.50-2.00) hours and 0.50 (0.25-2.00) hours, respectively. The extent of lamivudine and zidovudine absorption (AUC∞) and estimates of half-life following administration of lamivudine/zidovudine with food were similar when compared to fasting subjects, although the rates of absorption (Cmax, tmax) were slowed. Based on these data Lamivudine/Zidovudine Mylan may be administered with or without food.
Administration of crushed tablets with a small amount of semi-solid food or liquid would not be expected to have an impact on the pharmaceutical quality, and would therefore not be expected to alter the clinical effect. This conclusion is based on the physiochemical and pharmacokinetic data assuming that the patient crushes and transfers 100% of the tablet and ingests immediately.
Intravenous studies with lamivudine and zidovudine showed that the mean apparent volume of distribution is 1.3 and 1.6 l/kg respectively. Lamivudine exhibits linear pharmacokinetics over the therapeutic dose range and displays limited binding to the major plasma protein albumin (<36% serum albumin in vitro). Zidovudine plasma protein binding is 34% to 38%. Interactions involving binding site displacement are not anticipated with Lamivudine/Zidovudine Mylan.
Data show that lamivudine and zidovudine penetrate the central nervous system (CNS) and reach the cerebrospinal fluid (CSF). The mean ratios of CSF/serum lamivudine and zidovudine concentrations 2-4 hours after oral administration were approximately 0.12 and 0.5 respectively. The true extent of CNS penetration of lamivudine and its relationship with any clinical efficacy is unknown.
Metabolism of lamivudine is a minor route of elimination. Lamivudine is predominately cleared unchanged by renal excretion. The likelihood of metabolic drug interactions with lamivudine is low due to the small extent of hepatic metabolism (5-10%) and low plasma binding.
The 5'-glucuronide of zidovudine is the major metabolite in both plasma and urine, accounting for approximately 50–80% of the administered dose eliminated by renal excretion. 3'-amino-3'-deoxythymidine (AMT) has been identified as a metabolite of zidovudine following intravenous dosing.
The observed lamivudine half-life of elimination is 5 to 7 hours. The mean systemic clearance of lamivudine is approximately 0.32 l/h/kg, with predominantly renal clearance (>70%) via the organic cationic transport system. Studies in patients with renal impairment show lamivudine elimination is affected by renal dysfunction. Dose reduction is required for patients with creatinine clearance ≤50 ml/min (see section 4.2).
From studies with intravenous zidovudine, the mean terminal plasma half-life was 1.1 hours and the mean systemic clearance was 1.6 l/h/kg. Renal clearance of zidovudine is estimated to be 0.34 l/h/kg, indicating glomerular filtration and active tubular secretion by the kidneys. Zidovudine concentrations are increased in patients with advanced renal failure.
Pharmacokinetics in children
In children over the age of 5-6 months, the pharmacokinetic profile of zidovudine is similar to that in adults. Zidovudine is well absorbed from the gut and at all dose levels studied in adults and children, the bioavailability was between 60-74% with a mean of 65%. Cssmax levels were 4.45 μM (1.19 μg/ml) following a dose of 120 mg zidovudine (in solution)/m2 body surface area, and 7.7 μM (2.06 μg/ml) at 180 mg/m2 body surface area. Dosages of 180 mg/m2 four times daily in children produced similar systemic exposure (24 hour AUC 40.0 h μM or 10.7 h μg/ml) as doses of 200 mg six times daily in adults (40.7 h μM or 10.9 h μg/ml).
In six HIV-infected children from 2 to 13 years of age, zidovudine plasma pharmacokinetics were evaluated while subjects were receiving 120 mg/m2 zidovudine three times daily and again after switching to 180 mg/m2 twice daily. Systemic exposures (daily AUC and Cmax) in plasma from the twice daily regimen appeared equivalent to those from the same total daily dose given in three divided doses [Bergshoeff, 2004].
In general, lamivudine pharmacokinetics in paediatric patients are similar to adults. However, absolute bioavailability (approximately 55-65%) was reduced in paediatric patients below 12 years of age. In addition, systemic clearance values were greater in younger paediatric patients and decreased with age, approaching adult values around 12 years of age. Due to these differences, the recommended dose for lamivudine in children (aged more than three months and weighing less than 30 kg) is 4 mg/kg twice a day. This dose will achieve an average AUC0-12 ranging from approximately 3,800 to 5,300 ng h/ml. Recent findings indicate that exposure in children <6 years of age may be reduced by about 30% compared with other age groups. Further data addressing this issue are currently awaited. At present, the available data do not suggest that lamivudine is less efficacious in this age group.
Pharmacokinetics in pregnancy
The pharmacokinetics of lamivudine and zidovudine were similar to that of non-pregnant women.
The clinically relevant effects of lamivudine and zidovudine in combination are anaemia, neutropenia and leucopenia.
Mutagenicity and carcinogenicity
Neither lamivudine nor zidovudine are mutagenic in bacterial tests, but consistent with other nucleoside analogues, inhibit cellular DNA replication in in vitro mammalian tests such as the mouse lymphoma assay.
Lamivudine has not shown any genotoxic activity in in vivo studies at doses that gave plasma concentrations up to 40-50 times higher than clinical plasma levels. Zidovudine showed clastogenic effects in an oral repeated dose micronucleus test in mice. Peripheral blood lymphocytes from AIDS patients receiving zidovudine treatment have also been observed to contain higher numbers of chromosome breakages.
A pilot study has demonstrated that zidovudine is incorporated into leucocyte nuclear DNA of adults, including pregnant women, taking zidovudine as treatment for HIV-1 infection, or for the prevention of mother to child viral transmission. Zidovudine was also incorporated into DNA from cord blood leucocytes of infants from zidovudine-treated mothers. A transplacental genotoxicity study conducted in monkeys compared zidovudine alone with the combination of zidovudine and lamivudine at human-equivalent exposures. The study demonstrated that foetuses exposed in utero to the combination sustained a higher level of nucleoside analogue-DNA incorporation into multiple foetal organs, and showed evidence of more telomere shortening than in those exposed to zidovudine alone. The clinical significance of these findings is unknown.
The carcinogenic potential of a combination of lamivudine and zidovudine has not been tested.
In long-term oral carcinogenicity studies in rats and mice, lamivudine did not show any carcinogenic potential.
In oral carcinogenicity studies with zidovudine in mice and rats, late appearing vaginal epithelial tumours were observed. A subsequent intravaginal carcinogenicity study confirmed the hypothesis that the vaginal tumours were the result of long term local exposure of the rodent vaginal epithelium to high concentrations of unmetabolised zidovudine in urine. There were no other zidovudine-related tumours observed in either sex of either species.
In addition, two transplacental carcinogenicity studies have been conducted in mice. In one study, by the US National Cancer Institute, zidovudine was administered at maximum tolerated doses to pregnant mice from day 12 to 18 of gestation. One year post-natally, there was an increase in the incidence of tumours in the lung, liver and female reproductive tract of offspring exposed to the highest dose level (420 mg/kg term body weight).
In a second study, mice were administered zidovudine at doses up to 40 mg/kg for 24 months, with exposure beginning prenatally on gestation day 10. Treatment related findings were limited to late-occurring vaginal epithelial tumours, which were seen with a similar incidence and time of onset as in the standard oral carcinogenicity study. The second study thus provided no evidence that zidovudine acts as a transplacental carcinogen.
While the clinical relevance of these findings is unknown, these data suggest that a carcinogenic risk to humans is outweighed by the potential clinical benefit.
In reproductive toxicity studies lamivudine has demonstrated evidence of causing an increase in early embryonic deaths in the rabbit at relatively low systemic exposures, comparable to those achieved in man, but not in the rat even at very high systemic exposure. Zidovudine had a similar effect in both species, but only at very high systemic exposures. Lamivudine was not teratogenic in animal studies. At maternally toxic doses, zidovudine given to rats during organogenesis resulted in an increased incidence of malformations, but no evidence of foetal abnormalities was observed at lower doses.
Cellulose, microcrystalline (E460)
Colloidal anhydrous silica (E551)
Magnesium stearate (E572)
Tablet film coat:
Hypromellose (E464)
Propylene glycol (E1520)
After first opening: 60 days
This medicinal product does not require any special storage conditions
PVdC-PVC / Aluminium foil blister.
HDPE bottle and PP screw cap.
Lamivudine / Zidovudine Mylan is available in:
Pack sizes (blister): 30, 60, 60 x 1 (unit dose blister), 100 & 200 tablets
Pack sizes (bottles): 60 tablets
Mylan S.A.S
117 allee des Parcs,
69 800 Saint Priest
Building 4, Trident Place, Mosquito Way, Hatfield, Hertfordshire, AL10 9UL
+44 (0)1707 853 000 select option 2
http://www.mylan.com


text:
Sudbury, Ont., hospital memo reassures staff about current CEO, who's a former Laurentian University president | CBC News Loaded
Sudbury, Ont., hospital memo reassures staff about current CEO, who's a former Laurentian University president
The Sudbury, Ont., Health Sciences North (HSN) hospital board sent a memo to employees and medical staff last week to assure them the hospital is in good financial health.
Health Sciences North president and CEO Dominic Giroux led Laurentian University from 2009 to 2017
Jonathan Migneault · CBC News · Posted: Nov 28, 2022 6:00 AM EST | Last Updated: November 28, 2022
Dominic Giroux, now president and CEO of Health Sciences North in Sudbury, was president of Laurentian University from 2009 to 2017. (Markus Schwabe/CBC)
The memo came in the wake of a scathing report from Ontario Auditor General Bonnie Lysyk about Laurentian University that detailed poor management and a lack of transparency from 2010 to 2020, which led to the institution's insolvency in 2021.
From April 2009 to June 2017, Dominic Giroux was Laurentian's president. In 2017, he became the president and chief executive officer of HSN, and has remained in that role since then.
"We would imagine this situation has raised some questions for you on HSN and HSNRI's (Health Sciences North Research Institute) financial health given Dominic Giroux is a former president at Laurentian University," the memo to employees and medical staff said.
"We want to take a moment to provide some reassurance to you on our sound financial position, and convey our extraordinary confidence in Dominic Giroux as our president and CEO."
HSN memo Mobile users: View the document
HSN memo (PDF KB)
HSN memo (Text KB)CBC is not responsible for 3rd party content
The memo said that since Giroux joined the hospital, its cash position, working capital net assets and long-term debt have all improved.
"When Dominic Giroux took over five years ago, HSN was incurring a deficit of $1 million per month," the memo said.
"HSN incurred a surplus from hospital operations of $1.8 million in 2018-19, $0.3 million in 2019-20, $2.9 million in 2020-21 and $1.9 million in 2021-22."
The memo added that Giroux "has done an excellent job" co-chairing the pandemic response for the health sector in northern Ontario.
"We are fully confident in the job Dominic has done as CEO — a job that was recently validated by being chosen by his peers to be the chair of the Ontario Hospital Association at a time of great challenge in Ontario's health care sector," it said.
Bonnie Lysyk, auditor general of Ontario, released her special report on Laurentian University on Nov. 17. (Frank Gunn/The Canadian Press)
Report on Laurentian
In her special report on Laurentian, the auditor general put the primary blame for the university's financial collapse on a failed philosophy of "build it and they will come."
That started with what Lysyk called a poorly planned and costly capital expansion at a time in 2010 when the university was already facing financial difficulties.
From 2009-10 to 2019-20, Laurentian pursued six major capital projects that cost $168 million, including building the East Residence, a cardiovascular and metabolic research lab, the school of architecture, and campus modernization without adequate evidence or analysis to justify the investments.
"As the university began to amass more than $87 million in debt to pay for this capital expansion, the senior administration exacerbated the situation by making a series of questionable financial and operational decisions, including amending its internal policies to allow it to incur even more debt and increasing its senior administration's costs," Lysyk wrote in the report.
She also outlined how the president from 2009 to 2017 — Dominic Giroux — was given merit pay awards tied to pursuing the capital projects that contributed to the university's financial troubles.
The board approved the maximum bonus of $14,000 for Giroux each time a major capital project like the school of architecture was completed, even if they weren't always completed on time.
Poor management, new buildings led to Laurentian University insolvency, Ontario AG's preliminary report says
Ontario auditor general gives eye-opening details of Laurentian University's insolvency and the fallout
Lysyk added the costs associated with Laurentian's senior administrators climbed by 75 per cent from 2010 to 2020, which weakened the university's financial position and violated provincial rules.
"We also found that Laurentian breached provincial compensation-restraint legislation for broader public sector employees, compensating senior administration $389,000 more than legislation permitted, and that its recruitment of senior administrators lacked demonstrable fairness or rationale," she wrote.
CBC reached out to Dominic Giroux after the auditor general released her report, but he declined to comment.
Health Sciences North board chair Daniel Giroux — no relation to Dominic — was also not available for an interview about the hospital's memo by deadline.
With files from Kate Rutherford

redpajama_set_name: RedPajamaCommonCrawl


NEW PRODUCTS – Toolshed Coloring Book + Toolshed Journal « Adafruit Industries – Makers, hackers, artists, designers and engineers!
In 2013, illustrator Lee John Phillips began a project of one drawing a day, documenting the miscellanea from his late grandfather's shed. Phillips' "Shed Project" has enjoyed widespread coverage in the media and around the world.
"My grandfather, Handel Jones, died in 1994. His shed has remained relatively untouched. My grandmother treats it as a mausoleum.
He was a practical man and would spend a great deal of time in that shed fixing, salvaging, and making. Broken items were stripped of their parts and components sorted into relevant containers. Nothing was thrown away.
This lovingly commemorated and beautifully designed journal features 40 illustrations from Phillips' "Shed Project". With its wood effect cover and three different paper stocks, the Toolshed Journal is a wonderful memorial and daily journal. Pages are either blank or grid-ruled for illustrations or notes.
This boldly non-traditional Toolshed Coloring Book features 50 pages of over 1,400 beautiful, black and white illustrations, detailing the smallest hex nut to clamps and chisels. The last pages of the book are a dedicated inventory index, so you can look up what kind of tool you've lovingly colored in.


I've talked before about how I am a fan of Sorcerers of the Magic Kingdom, particularly the collecting aspect of the game. I was one of those kids who played many a collectible card game in my day, more like rabidly collected the cards that I thought were amazingly cool from games like Magic and Star Wars and was afraid to play with them because they would get damaged, but you get the idea.
Each card from Sorcerers of the Magic Kingdom has five main elements: the name, image, type of spell, type of Attack/Boost/Shield, and two lines of playful text that explain the story of the card.
The stories cards can tell have always been fascinating to me. The imagery and ability of the cards, whether it is Sorcerers of the Magic Kingdom or Magic – The Gathering, is about as far as most players really delve into the story each presents. Sure the abilities are important, although in Sorcerers of the Magic Kingdom it seems to make very little difference to the game itself whether a guests uses a certain type of spell or ability type, such as Machine Spell or Princess Spell with an Energy Attack or Wishful Attack. However, I'm sure an analytically minded enthusiast could sit down and pound out rules for the game so it could be played at home in a matter of hours. Meanwhile, the pictures facilitate the progression of a story much in the same way the art of comic books do, but there is a lot to be gleamed from the other text found on the cards.
For me, the story begins with the name of the card and the two lines of text, known as flavor (because they add a sense of time and place), is where the true story lies. Take one of my favorites as an example: Baloo's Coconut Cascade, which reads, "Watch your step if you're a klutz/Or you'll be crowned with coconuts." It has witty wordplay in the title, a nice rhyming couplet, and it tells you what you are in for with the card.
The first set of cards, 70 in total, with 10 cards that have still not been made available to guests who did not partake in the testing of Sorcerers of the Magic Kingdom, pulled characters from all across the world of Disney animation. There are a smattering a villains included in the set, and I'd love to see a full set of villains to see villains smashing other villains in a baddie-royale rumble, but very few characters from Walt Disney World.
With that in mind, I started playing with the idea of creating a set based on the adventures that take place inside the Magic Kingdom and Walt Disney World beyond. I shared a pair of these with followers on Twitter, and thought I'd share some more with you here. Below are some, not all, of the cards I've been messing around with. I didn't try to come up with each card's Attack/Boost/Shield numbers, but rather created the home story for the cards with a name, spell type, and the two lines of text. It's all done in fun and games, but given a nice, new world to play in, I couldn't resist playing in it myself. I hope you have as much fun imagining these cards in your mind as I did putting them together!
Beast's Bellow – Warrior Spell – This bark is worse than its bite/But this roar will show your might.
Big Al's Guitar – Animal Spell – Pluck, pick, and strum away/The music can keep the dark at bay.
Buddy Boil's Hypnotic Wheel – Monster Spell – Reading minds is a wizard's shtick/Master this and you'll be pretty slick.
Carnotaurus' Chomp – Animal Spell - Wizards leave giant footsteps to follow/But don't bite off more than they can swallow.
Constance's Cleaver Throw – Mystic Spell – It may be a ghastly sight/But this cleaver is a villain's fright.
Figment's One Little Spark – Monster Spell – It's a spark of inspiration/And soon you'll be an imaginative sensation.
I.B. Hearty's Rockslide – Machine Spell – You may not conduct this train/But it can make the boulders rain.
Little Orange Bird's Orange Thoughts – Animal Spell – Be mindful of the Sunshine Tree/Or all your thoughts orange will be.
Merida's Will-O'-The-Wisp – Princess Spell – You'll change your fate in no time flat/When these blue wisps show you where you're at.
Miss Tilly's Water Eruption – Machine Spell – She may be stuck on Mount Mayday/But a watery blast will wash you away.
Pierre's Beak Assault – Hero Spell – If you think they're just for singing/Ignoring these birds will leave your ears ringing.
Shrunken Ned's Shrunken Head Toss – Hero Spell – Three of his for one of yours/A cascade of heads will give you sores.
The Caretaker's Lantern – Hero Spell – When you stumble upon something scary/Shine your lantern to make ghosts merry.
The Great Goofini's Safety Net – Hero Spell – Safety first, make it nice and strong/Precautions make magic hum along.
The Helmsman's Swashbuckling Sword – Warrior Spell – If the high seas shake your bones/You'll find this sword strikes better than stones.
The Small World Dolls' Smile – Toy Spell – It's time you're aware/A smile can scare away your nightmare.
Timothy Mouse's Magic Feather – Animal Spell – To fly you don't need oversized ears/Just this totem to face your fears.
Tinker Bell's Pixie Dust – Fairy Spell – Inhaling it may make you sneeze/But flying high is the bee's knees.
Tom Sawyer's Paintbrush – Hero Spell – Sling this brush at your foe/Paint them all from head to toe.
Zurg's Secret Weapon – Toy Spell – It may take a lot of batteries/So use it only in emergencies.
They already have a Tinker Bell card!


text:
Hippopotamus pentlandi is an extinct species of hippopotamus from Sicily, known from the late Middle Pleistocene to early Late Pleistocene. It is the largest of the insular dwarf hippos known from the Pleistocene of the Mediterranean, "at most 20% smaller than the mainland forms", with an estimated body mass of approximately 1100 kg. It is suggested that it arrived in Sicily between 250,000 and 150,000 years ago, probably descending from the modern hippopotamus (Hippopotamus amphibius), with an origin from Hippopotamus antiquus being less likely. In comparison to those species, the muzzle was shorter, the occipital and nasal regions were more developed, the mastoid process was enlarged, and the dental row was shortened, and the condyle of the mandible is low. In comparison to H. amphibius, the orbits are also elevated. It was present in Sicily until at least the latest Middle Pleistocene around 120 kya, and was probably extinct by the beginning of Marine Isotope Stage 4 (~71,000 years ago). Contemporaneous species include the dwarf elephant Palaeoloxodon mnaidriensis, the aurochs, red deer, steppe bison, fallow deer, wild boar, brown bear, wolves, red foxes, cave hyena and cave lions. Its diet was likely grazing dominated, similar to that of modern H. amphibius. It is probably ancestral to Hippopotamus melitensis from Malta, which is substantially smaller than H. pentlandi.

See also
 Cyprus dwarf hippopotamus
 Cretan dwarf hippopotamus

References

External links
Ferrara University Museum Photo of Hippopotamus pentlandi

Extinct hippopotamuses
Prehistoric mammals of Europe
Pleistocene even-toed ungulates
Messinian
Fossil taxa described in 1832

redpajama_set_name: RedPajamaWikipedia


text:
Q: Using local JSON to mock Firebase for testing? I'm thinking about a testing strategy for an app that uses Firebase for its datastore.  While it's fine for end-to-end tests to make requests to the actual backend, it would be nice to be able to make unit tests of app logic that don't have to go out to Firebase.
I've been scouring the web for a way to use something like a local JSON file to mock the javascript Firebase service, but haven't found anything.  Does something like this exist?  If not, I'll write it and post it on github...

A: Update
See this gist and this post for a detailed exploration of encapsulated TDD vs. using mocks for unit testing.
Original Post
It would be very difficult to properly mock a Firebase service, as it would be to mock most sophisticated data stores. Think of this in terms of mocking MySQL or mocking MongoDB.
Assuming your goal is to make the local environment work offline, a quick solution might be to use a local instance. You can grab the firebase-debug.js, save it locally, and call set(/* data */) to initialize it for offline ops.
Otherwise, your best approach would be to encapsulate all the Firebase activity to one class or library. Then you can mock that library rather than your Firebase events. And to quasi-unit test (these are technically not unit tests since they depend on an external service) the library itself, fall back to a local offline Firebase instance or set up a dev database and copy your production data (or some seed data) there.

redpajama_set_name: RedPajamaStackExchange


HA HA HA! I'm afraid i don't know this man, but if it is any consolation i too attract weirdos and have had to fend off a fair few nutters in my time.
I also had a male friend who worked in the shop with me last year. This big fat dude used to come in every other day and ask for my friend after he helped him once. We all got into the habit of ringing up to men's floor to warn him he had just walked through the door so he had a chance to run up the stairs and hide in the stockroom. This went on for a few months and when he was cornered he had to help this bloke for up to an hour whilst he wandered around with his trousers around his ankles asking him to fetch jeans. Horrible for my friend, wonderfullly amusing for us.
picking on fat people and weirdos just shows you have no sense of morality. How can you put the picture of a guy from warwick (one of us) on warwick blogs and called him a weirdo? also philippa so what if this guy was fat your not exactly Kate Moss yourself. beauty is only skin deep, something you might want to think about in 20 yrs from now.
Jodie, i'm afraid the weirdos are everywhere, i continue to attract them wherever i go, and there is nothing i can do to prevent it. Sorry hun!
Very sorry to offend u Lee!! And yes u are very right about him being from Warwick and hence, not so wierd but nevertheless I do maintain that i attract 'em and its not fun!!
Dude, I've met some of the weirdest people I know at Warwick!
Hey Lee, thanks, you seriously made me consider my morality!! But hey u were the one who was drunk!! But I seriously dnt know his pic would come up like that, that is a bit harsh, so how do i get it off, do I just delete it??? And, well done on ur exams so early in the new yr!!
whenever you create a new post there is an option to say whether or not to show it in the "all blogs" collection. entries are constantly being added so it is unlikely your post was visible for very long. The most intresting thing that most people do not realise is that Google indexing our blogs every few weeks. Type your name into google and the first result is your blog. the next time Google indexes your blog it will index the word weirdo such that anyone that types "warwick + weirdo" is likely to find your post.


Finnish GREBE partner Karelia University of Applied Sciences (Karelia UAS) provides higher education for the needs of changing national and regional industry, commerce and other working life. Karelia UAS also develops and offers research and development services and enhances regional development, especially in North Karelia and Eastern Finland. The strategic focus areas of Karelia UAS include sustainable energy and materials, and modern welfare services.
The GREBE project includes business development activities of renewable energy and energy efficiency in northern peripheral context. In GREBE, Karelia UAS has the lead of work package 6 "Business Models and Business Development Support" and activities especially for developing business growth strategies for SMEs and start-ups and improving the market access of renewable energy and energy storage technologies.
A business growth survey is launched in April 2016 in order to analyse the opportunities of RE business growth, and to identify the current business support needs. At the end, this will result in Growth Strategy Guideline for the use of business enterprises in the sector. The RE business growth and start-ups will also be supported through the developed GREBE service, Entrepreneurship Enabler Scheme (EES). It is expected to provide international and innovative mentoring support for the RE and energy storage industries.


text:
Sir Henry Morton Stanley (* 28. Januar 1841 als John Rowlands in Denbigh, Wales; † 10. Mai 1904 in London), auch Bula Matari ("der die Steine bricht"), war ein britisch-amerikanischer Journalist, Afrikaforscher und Buchautor. Er wurde bekannt durch die Suche nach David Livingstone und die Erforschung sowie die Erschließung des Kongo im Auftrag des belgischen Königs Leopold II. Stanleys Literaturagent war G. W. Appleton.

Kindheit (1841–1856)

Das Geburtsregister der walisischen Stadt Denbigh vermeldet für den 28. Januar 1841 die Geburt eines nichtehelichen Kindes: "John Rowlands, Bastard". Unter seiner nichtehelichen Geburt sollte der spätere Henry Morton Stanley sein Leben lang leiden. Seine Mutter, Betsy Parry, arbeitete als Hausmädchen und gebar in den kommenden Jahren noch vier weitere nichteheliche Kinder. Wer sein Vater war, erfuhr er nie. Es gibt Spekulationen, es könne John Rowlands gewesen sein, ein stadtbekannter Trinker, oder ein verheirateter Anwalt namens James Vaughan Home.

Das Kind kam zunächst in die Obhut des Großvaters. Nach dessen Tod – Henry Morton Stanley war zu diesem Zeitpunkt fünf Jahre alt – gab ihn sein Onkel zunächst zur Pflege in eine Familie und später, als er das Pflegegeld nicht mehr zahlte, in das Arbeitshaus St. Asaph's Union Workhouse in dem kleinen Ort St Asaph. Später stellte eine Untersuchung fest, dass die älteren Bewohner des Hauses "allen möglichen Lastern anhingen". Der Leiter, ein Alkoholiker, nahm sich gegenüber den Bewohnern alle Freiheiten heraus. Die Kinder teilten zu zweit die Betten, und wenn sie nicht von Erwachsenen missbraucht wurden, dann quälten die Älteren die Jüngeren, auch nachts.

Immerhin vermittelte der Aufenthalt in diesem Arbeitshaus ihm eine gewisse Schulbildung. Er war ein guter Schüler, besonders an Geographie interessiert, und erhielt für seine guten Leistungen eine Bibel mit Widmung des Bischofs.

Seine Mutter traf Henry in dieser Zeit nur ein einziges Mal, als er etwa neun war, und sie zwei weitere Kinder nach St. Asaph brachte.

Amerika (1856–1861)
Mit 15 Jahren verließ er das Arbeitshaus, freiwillig – anders als er es selbst darstellte. Er arbeitete in verschiedenen Stellungen als Tagelöhner und heuerte schließlich mit 17 Jahren auf der Windermere an, einem Schiff, das nach New Orleans segelte. Dort angekommen suchte er Arbeit und stellte sich dem Baumwollhändler Henry Hope Stanley vor, den er mit seiner Preisbibel beeindrucken konnte.

Rowlands Schilderungen dieser Zeit – und wohl nicht nur dieser – weichen von der Wirklichkeit ab. Er schreibt, er habe bei den Stanleys gewohnt, sei adoptiert worden und habe das Ehepaar Stanley auf Reisen begleitet. Doch leider sei erst die Frau und dann ganz plötzlich auch der Mann im Jahre 1861 gestorben. Nach dem Melderegister der Stadt New Orleans starb der ältere Stanley erst 1878, siebzehn Jahre später. Er und seine Frau hatten zwar zwei Kinder adoptiert, doch beide waren Mädchen. Sein junger Angestellter Rowlands hatte auch nie bei ihm gewohnt, und schließlich zerstritten sich Rowland und Henry Hope Stanley derart, dass sie den Kontakt zueinander abbrachen.

Soldat und Schreiber (1861–1867)

1861 trat der junge Mann, der sich nun Henry Stanley nannte (Morton fügte er später hinzu), der Konföderierten Armee bei, um im Amerikanischen Bürgerkrieg zu kämpfen. Im April 1862 wurde er bei der Schlacht von Shiloh in Tennessee gefangen genommen und in ein Kriegsgefangenenlager bei Chicago gebracht. Wer zu den Truppen der Union überlief, durfte das Lager verlassen. Da im Gefangenenlager Typhus umging, entschied sich Stanley für diesen Schritt. In der Armee der Nordstaaten erkrankte er und wurde daraufhin ausgemustert.

Er heuerte zuerst auf verschiedenen Schiffen der Handelsmarine und im Jahre 1864 erneut bei der Kriegsmarine der Union an. Wegen seiner schönen Handschrift machte man ihn zum Schiffsschreiber auf der Minnesota. Kurz vor dem Kriegsende 1865 desertierte er und schlug sich nach St. Louis durch, wo er einen Vertrag als freier Korrespondent einer Lokalzeitung bekam. Er schrieb Berichte aus dem Wilden Westen: Denver, Salt Lake City, San Francisco. Im Tross von Generalmajor Hancock nahm er an den Indianerkriegen teil. Obwohl das Jahr seiner Berichterstattung von Friedensverhandlungen geprägt war, schrieb er über die dramatischen Schlachten, die sein Verleger erwartete. Damit erweckte er das Interesse von James Gordon Bennett Jr., dem Herausgeber des New York Herald, einer Boulevardzeitung.

New York Herald (1867–1878)
Bennet erkannte Stanleys journalistisches Talent und schickte ihn als Kriegsberichterstatter nach Abessinien, um von den dortigen Unruhen zu berichten. Stanley bestach auf der Durchreise in Ägypten den Cheftelegrafen und stellte so sicher, dass seine Berichte von der Front auch dann zuerst telegrafiert wurden, wenn andere Berichte vorher eingetroffen waren. Das Glück war mit ihm. Ausgerechnet am Tag nach der einzigen wichtigen Schlacht riss das Telegrafenkabel nach Malta, unmittelbar nachdem Stanleys Bericht (als einziger) übertragen worden war. Sein Verleger war begeistert.

Der Herald machte ihn zum festangestellten Sonderkorrespondenten und schickte ihn in der Folgezeit unter anderem nach Spanien, um vom dortigen Bürgerkrieg zu berichten, bei dem Königin Isabella II. ihren Thron verlor. In Madrid, so will es Stanleys eigene Legende, erreichte ihn am 16. Oktober 1869 ein Telegramm seines Verlegers, das ihn sofort nach Paris beorderte. Dort erteilte ihm Bennett den Auftrag "Finden Sie Livingstone!"

 "Draw a thousand pounds now, and when you have gone through that, draw another thousand, and when that is spent, draw another thousand. . . and so on; but find Livingstone!"

Afrika

Die Suche nach Livingstone (1870/71)
Vom schottischen Missionar und Afrikaforscher David Livingstone, einem Arzt, der im Auftrag der London Missionary Society unterwegs war, gab es seit seinem Aufbruch zu einer Forschungsreise in das Gebiet der ostafrikanischen Seen 1866 kein Lebenszeichen mehr. Obwohl Stanley die Geschichte später sehr dramatisch darstellte, brach er erst ein ganzes Jahr später auf. Zwischendurch berichtete er für seine Zeitung noch von der Eröffnung des Sueskanals, von Ausgrabungen in Jerusalem und schließlich aus Konstantinopel. Erst 1870 brach er von Bombay aus auf, um Livingstone zu finden.

Wie er es im Abessinienkrieg gelernt hatte, brach er mit einem riesigen Tross auf, 190 Männer, nur zwei weitere Briten, die übrigen afrikanische Träger. Er bewegte sich von Osten her Richtung Zentralafrika und begegnete am 10. November 1871 in Ujiji, in der Nähe des Tanganjikasees einem Europäer. "Doctor Livingstone, I presume?" – "Doktor Livingstone, nehme ich an", soll er gesagt haben. Da Stanleys europäische Begleiter die Reise nicht überlebten, die Afrikaner nie befragt wurden und Livingstone bis zu seinem Tod ein Jahr später nichts aufschrieb, liegt nur Stanleys Bericht vor.

Die beiden Männer waren sehr verschieden: Hier der Missionar Livingstone, der Afrika und die Afrikaner liebte, ihre Sprachen lernte und keinen Profit aus seinen Reisen zog. Dort Stanley, der ehrlich zugab, den Kontinent von ganzem Herzen zu verabscheuen. Seine Bücher über Afrika hießen dann auch Durch den dunklen Weltteil oder Im dunkelsten Afrika.

Während Stanley in Afrika war, schrieb er seiner Verlobten Katie Gough-Roberts, einer jungen Frau aus seiner Heimatstadt Denbigh, viele Briefe, die er ihr von Häfen aus auch schickte. In einem gestand er seine wahre Herkunft, uneheliche Geburt und unglückliche Kindheit. Nach seiner Rückkehr musste er feststellen, dass sie in der Zwischenzeit einen anderen geheiratet hatte. Stanley, der zeit seines Lebens Angst hatte, seine Herkunft könne bekannt werden, versuchte, diese Briefe wieder an sich zu bringen, doch vergebens.

Die Royal Geographical Society empfing Stanley mit Hochmut, denn auch sie hatte eine Expedition ausgeschickt, Livingstone zu finden, doch zu spät. Die Echtheit der Briefe, die er von Livingstone mitgebracht hatte, wurde angezweifelt, und Königin Victoria empfing ihn zwar, urteilte danach aber, er sei ein "grässlicher kleiner Mann".

Zweite Afrikaexpedition, 1874–1877
Ziel der zweiten Expedition war es, herauszufinden, woher der Nil kommt. Livingstone dachte, der Lualaba sei die Quelle des Nils, während der Brite John Speke dachte, der Nil entspringe am Nordufer des Viktoriasees. Doch Stanley wollte außerdem beweisen, dass der Erfolg bei seiner ersten Reise kein Zufallstreffer war. Er zog nicht nur mit 359 Mann los, sondern hatte ein Schiff dabei, die Lady Alice, in Einzelteile zerlegt. Das Schiff war nach seiner Verlobten Alice Pike benannt, nach der er noch einige geographische Entdeckungen benennen sollte, etwa Alice Island und Alice Rapids. Doch nach seiner Rückkehr musste er (wieder einmal) feststellen, dass die Verlobte unterdessen einen anderen, einen Eisenbahnbesitzer aus Ohio, geheiratet hatte.

Nach nur drei Monaten waren bereits 150 Männer gestorben – teils von feindseligen Stämmen ermordet, teils durch Krankheiten, teils von Stanley in den Tod getrieben. Stanley, der selbst die Fronten gewechselt hatte und desertiert war, kannte keine Gnade gegenüber Deserteuren. Sie erwartete die Nilpferdpeitsche, oder sie wurden in die Sümpfe getrieben.

Seine Expedition dauerte fast 1000 Tage. Er legte etwa 11.000 Kilometer zurück. Von seinen weißen Gefährten überlebte wieder keiner. Bei seiner Ankunft in Boma an der Kongomündung war Stanley 36 Jahre alt, doch durch die Strapazen ausgemergelt und früh weißhaarig. In Uganda entdeckte er 1876 einen weiteren See, den er nach Albert Edward benannte (Edwardsee). Er schrieb erste Artikel, nach seiner Rückkehr nach England hielt er Vorträge und schrieb Bücher.

Er war bestrebt, Zentralafrika und den Kongo dem britischen Kolonialreich einzugliedern, doch im Vereinigten Königreich ging niemand auf seine Ideen ein.

Leopold II. und der Kongo
Leopold II. von Belgien las seine Berichte. Der junge Monarch war bestrebt, Kolonien zu erwerben. Mehrere Versuche, solche zu erlangen, waren bereits fehlgeschlagen. Leopold hatte zunächst eine philanthropische Gesellschaft zur Erforschung des Kongo gegründet. Im September 1876 veranstaltete er eine große geographische Konferenz in Brüssel, bei der es um die Erforschung des Kongos ging.

Am 10. Juni 1878 traf er Stanley und die beiden gingen einen Handel ein. Stanley sollte den Kongo für den König erwerben, Leopold würde dafür sorgen, dass formal alles in Ordnung kam. Sie schlossen einen Fünfjahresvertrag ab. Stanley erhielt Geld von diesem, musste jedoch zusätzliche Mittel zur Finanzierung seiner Expeditionen einwerben. Er ging auf Vortragsreise und konnte sogar Missionsgesellschaften dazu bringen, Geld zu spenden.

Stanley sammelte unterdessen Kaufverträge für das Land rund um den Fluss. Die Stammesfürsten und Häuptlinge, die die Papiere in der ihnen unbekannten Sprache unterschrieben, wussten wohl nicht, was sie taten. Eine Klausel der Verträge besagte, dass nicht nur der Boden, sondern auch die Arbeitskraft der Bewohner in den Besitz von Leopold übergehen.

Fünf Jahre lang war Stanley offiziell Leopolds Vertreter im Kongo und begann mit dem Bau einer Piste von der Mündung des Flusses Kongo entlang der Kongofälle, 200 km lang, bis Stanley Pool (heute Pool Malebo), von wo aus der Kongo schiffbar war. Bei diesem Projekt kamen viele der zwangsweise rekrutierten Einheimischen um. Stanleys teilweise rücksichtsloses Vorgehen wurde in England stark kritisiert und brachte ihm den afrikanischen Spitznamen Bula Matari ("der die Steine bricht") ein.

Kleine Dampfschiffe wurden stückweise zum Stanley Pool geschafft und zusammengebaut. Stanley gründete eine Stadt, die er nach seinem Gönner Leopoldville nannte (heute Kinshasa). An 1500 Kilometern Flusslauf entlang wurden weitere Stationen geplant und gebaut. All dies, so wurde es nach außen dargestellt, im Dienste der Wissenschaft und im Kampf gegen die Sklaverei.

Trotz all dieser Aktivitäten konnten Stanley und Leopold zunächst ihren guten Ruf erhalten. 1884 nahm Stanley an der internationalen Kongokonferenz teil, die auf Initiative Bismarcks in Berlin stattfand. Der Kongo wurde Leopold als persönlicher Besitz zugesprochen, damit er ihn entwickle. Offiziell trennten sich die Wege von Leopold und Stanley nach fünf Jahren, doch heimlich stand Stanley weiter auf der Gehaltsliste des Königs.

1889 fand in Brüssel eine große Konferenz gegen die Sklaverei statt. Sklavenhändler waren traditionell arabische Kaufleute, die Konferenz stellte also für die europäischen Teilnehmer kein Problem dar. Leopold ließ Stanley auf dieser Konferenz auftreten, um seine Position auf der Konferenz zu festigen und gleichzeitig dem belgischen Parlament einen Kredit von 25 Millionen Franken zu entlocken. Stanleys Wirken hatte es ermöglicht, dass eine Privatperson – Leopold II. – der Besitzer von 2,5 Millionen Quadratkilometern Land sowie der Arbeitskraft der Einwohner wurde.

Die Emin-Pascha-Expedition

Unterdessen nahm Stanley aber auch andere Aufträge an. Im Sudan, der ab 1821 unter die Herrschaft der osmanischen Vizekönige von Ägypten gekommen war, brach 1881 der Mahdiaufstand aus. Nach dem Abzug der anglo-ägyptischen Truppen aus dem Sudan behauptete sich der deutsche Forscher Emin Pascha als Gouverneur der südlichsten Provinz des Sudan Äquatoria. Emin Pascha, bürgerlich Eduard Schnitzer, musste erfahren, dass die Briten keine Anstalten machten, den Sudan zurückzuerobern. Er schrieb deshalb einen Brief an die Times, in dem er um Hilfe bat. Gleichzeitig forderte der Anführer der Mahdisten Abdallahi ibn Muhammad, dass Königin Victoria in den Sudan kommen und zum Islam konvertieren solle. Die daraus resultierende Empörung in der britischen Bevölkerung führte dazu, dass rasch die finanziellen Mittel für eine Expedition zur Befreiung Emin Paschas aufgebracht wurden. Stanley wurde beauftragt, die Expedition zu leiten. Er musste Leopold bitten, ihn von seinen Verpflichtungen zu entbinden. Das tat dieser unter der Bedingung, dass Stanley nicht den kürzesten Weg nehme, sondern durch einen noch unbekannten Teil des Kongo reisen müsse. Außerdem sollte er Emin Pascha überreden, als Gouverneur zu bleiben, sich aber dem Kongo zu unterstellen. Die Expedition, die bereits nach Sansibar aufgebrochen war, wurde deshalb zur Mündung des Kongo umgeleitet.

Stanley bereitete die Reise gut vor, einige Aspekte muten geradezu skurril an. Die mitreisenden Offiziere mussten sich verpflichten, keine Bücher über die Expedition zu veröffentlichen. Das Dampfschiff, das die Gruppe auf dem Unterlauf des Kongo transportierte, hatte die Fahne des Yachtklubs von New York gehisst, auf Wunsch des Verlegers James Gordon Bennett Jr. Die Truppe von 389 Mann war stark dezimiert, als sie Emin Pascha schließlich gegenüberstand. Dieser trug, wie Stanley selbst notierte, eine blütenweiße, frisch gebügelte Uniform, und man fragte sich, wer da wen gerettet hatte, zumal die Vorräte der "Befreier" erschöpft waren.

Stanley konnte Emin Pascha mit knapper Not überreden, mit ihm zu kommen, aber diesmal auf der kürzeren Route, Richtung Osten. Zu Stanleys Unglück konnte er ihn nicht überreden, in die Dienste Leopolds zu treten; er entschloss sich, für die Deutschen zu arbeiten.

Obwohl die Expedition alles andere als ein Erfolg war, wurde Stanley bei seiner Rückkehr nach Europa ein triumphaler Empfang bereitet. Er wurde mit Ehrungen überhäuft, erhielt Medaillen mehrerer europäischer wissenschaftlicher Gesellschaften und Ehrendoktorwürden der Universitäten Oxford, Cambridge, Durham und Edinburgh. Zu einem Empfang, den die Royal Geographical Society ihm in der Royal Albert Hall gab, kamen 10.000 Gäste, darunter auch der Prince of Wales.

Heirat und Rückzug (1890–1904)

Am 12. Juli 1890 heiratete Stanley die Gesellschaftsmalerin Dorothy Tennant. Sie hatte ihn einige Jahre zuvor verschmäht, doch nach der Rettung Emin Paschas begonnen, ihm Briefe zu schreiben. Mehrere Biographen Stanleys, darunter Frank McLynn, gehen davon aus, dass die Ehe nie vollzogen wurde, aber die Stanleys adoptierten 1896 einen Sohn, Denzil Stanley. Stanley hatte außerdem eine besondere Beziehung zu Edward James Glave, den er von seinem Aufenthalt in Kongo in Diensten des Leopold II. kannte und als seinen Ziehsohn betrachtete.

Es gefiel Stanley, nicht mehr allein zu sein. Er reiste nur noch in "zivilisierte Gegenden", wo er Vorträge hielt und seine Bücher vorstellte. Von einer Vortragsreise nach Australien zurückgekehrt, ließ er sich 1892 in England wiedereinbürgern und gehörte von 1895 bis 1901 dem Unterhaus an, wo er sich der Liberalen Unionistischen Partei anschloss. Im Oktober 1897 reiste er einer Einladung zur Eröffnung der Bulawayo Railway folgend, durch Südafrika, besuchte die Transvaal-Republik, den Oranje-Freistaat sowie Natal und traf in Pretoria Paul Kruger. 1899 wurde er zum Knight Grand Cross des Order of the Bath (GCB) geschlagen.

Die Nachrichten von den Gräueltaten im Kongo erreichten jedoch unterdessen England. Edmund Dene Morel, ein junger Mann, der im Transportgewerbe arbeitete, hatte in den neunziger Jahren festgestellt, dass Schiffe aus dem Kongo eine Menge Waren brachten, vor allem Elfenbein und Gummi, aber dass auf dem Rückweg nur Munition transportiert wurde. Er startete die wohl erste Menschenrechtskampagne der Geschichte, gab einen regelmäßigen Rundbrief heraus und korrespondierte mit Missionaren und Kongoreisenden, unter anderem dem Schriftsteller Joseph Conrad, die ihn mit Informationen versorgten.

Als Stanley am 10. Mai 1904 in London starb, war die Stimmung umgeschlagen. Der Dekan der Westminster Abbey, J. Armitage Robinson, verweigerte ihm seinen Wunsch, ein Begräbnis in der Westminsterabtei an der Seite Livingstones. Er wurde stattdessen in seinem letzten Wohnort, Pirbright in Surrey, beigesetzt. Seine Frau ließ ihm einen Grabstein mit der Inschrift "Henry Morton Stanley, Bula Matari, 1841–1904, Africa" errichten.

Veröffentlichungen
Stanleys Bücher über Afrika enthalten sehr viele Details. In Durch den dunklen Weltteil gibt es über hundert Zeichnungen, unter anderem Pläne afrikanischer Häuser, Pläne typischer Dörfer, Zeichnungen von Schlachten, Vergleich verschiedener afrikanischer Kanupaddel. Tabellen informieren über die Luft- und Wassertemperatur, die Tiefe der verschiedenen Seen, oder über den Preis eines Huhnes. Seine Bücher enthalten auch oft Auszüge seiner Tagebücher, allerdings haben diese mit den wirklichen Tagebüchern oft nicht so viel zu tun. Dort führte er beispielsweise Buch über die Bestrafung von Trägern: "Die beiden Betrunkenen zu 100 Peitschenhieben verurteilt, danach 6 Monate in Ketten."

 How I found Livingstone. Travels, adventures and discoveries in Central Africa including four months residence with Dr Livingstone, London 1872
 Coomassie and Magdala: The Story of two British Campaigns in Africa, London 1874
 My Kalulu, Prince, King, and Slave, London 1874
 Through the dark continent, or the sources of the Nile, around the great lakes of Equatorial Africa and down the Livingstone river to the Atlantic Ocean, London 1878
 Stanley's first Opinions: Portugal and the Slave Trade, Lissabon, 1883
 The Congo, and the Founding of its Free State, 1885, zuletzt aufgelegt in Detroit 1970, ISBN 0-403-00288-5
 In Darkest Africa: Or the Quest, Rescue, and Retreat of Emin, Governor of Equatoria, London 1890 (Digitalisat: Band 1, Band 2)
 The story of Emin's rescue as told in Stanley's letters, London 1890, zuletzt New York 1969, ISBN 0-8371-2177-9
 My dark Companions and their strange stories; Slavery and the Slave Trade in Africa, 1893
 My Early Travels and Adventures in America and Asia, London 1895, ISBN 0-7156-3085-7
 Through South Africa, 1898
 Africa, its Partition and its Future, 1898

Postum veröffentlicht

 The Autobiography of Sir Henry Morton Stanley: The Making of a 19th Century Explorer, London 1909, ISBN 1-58976-010-7
 H. M. Stanley: Unpublished Letters, 1961
 Stanley's Dispatches to the New York Herald 1871–1872, 1874–1877 Boston 1970, herausgegeben von Norman R. Bennet
 The story of Emin's rescue as told in Stanley's letters, New York 1969, herausgegeben von J. Scott Keltie, ISBN 0-8371-2177-9

In deutscher Sprache

 Wie ich Livingstone fand. Reisen, Abenteuer u. Entdeckungen in Central-Afrika (= Originaltitel: How I found Livingstone), Brockhaus / Reclam, Leipzig 1879; Neuausgabe: herausgegeben von Heinrich Pleticha, (= Alte abenteuerliche Reiseberichte). 3. Auflage, Edition Erdmann, Stuttgart / Wien 1995, ISBN 3-522-60480-6, 2012: ISBN 978-3-86539-832-1.
 Durch den dunkeln Welttheil oder die Quellen des Nils, Reisen um die grossen Seen des aequatorialen Afrika und den Livingstone-Fluss abwärts nach dem atlantischen Ocean, aus dem Englischen von C. Böttger, Leipzig 1878
 Der Kongo und die Gründung des Kongostaates. Arbeit und Forschung. Aus dem Englischen von H[ugo] von Wobeser. 2 Bände. F. A. Brockhaus, Leipzig 1885.
 Im dunkelsten Afrika. Aufsuchung, Rettung und Rückzug Emin Pascha's, aus dem Englischen von H. von Wobeser. Leipzig 1890
 zus. mit A[rthur] J. Mounteney Jephson: Emin Pascha und die Meuterei in Aequatoria. Neunmonatlicher Aufenthalt und Gefangenschaft in der letzten der Sudan-Provinzen. Aus dem Englischen von H[ugo] von Wobeser. F. A. Brockhaus, Leipzig 1890.
 Mein Leben (2 Bände), aus dem Englischen von Achim von Klösterlein und Gustav Meyrink. Verlag Die Lese, München 1911

Angegeben ist jeweils die Erstausgabe.

Siehe auch
 Liste europäischer Afrikaforscher

Literatur
In chronologischer Reihenfolge:

 Walter Bauer: Die Schwarze Sonne. Die Geschichte von Henry Morton Stanley. Mit Illustrationen von Hans Peters. Verlag Henri Nannen – Hannoversche Verlagsgesellschaft, Hannover 1948 (Die Bunten Hefte. Nr. 3, 1948, ).
 Hans-Otto Meissner: Der Kongo gibt sein Geheimnis preis. Die Abenteuer des Henry M. Stanley. Cotta, Stuttgart 1968 (Nachdruck: Mundus Verlag, Stuttgart 1982, ISBN 3-12-920041-X (Die Abenteuer der Weltentdeckung 9)).
 Quirin Engasser (Hrsg.): Große Männer der Weltgeschichte. 1000 Biographien in Wort und Bild. Neuer Kaiser Verlag, Klagenfurt 1987, ISBN 3-7043-3065-5, S. 441.
 P. Werner Lange: Henry Morton Stanley. Sein Weg nach Afrika, Verlag Neues Leben, Berlin 1990 und Edition Erdmann, Stuttgart 1990 (dort als Henry Morton Stanley. Die Biographie).
 Frank McLynn: Stanley. The Making of an African Explorer. Oxford University Press, Oxford 1991, ISBN 0-8128-4008-9 (Oxford lives).
 Adam Hochschild: King Leopold's Ghost. A Story of Greed, Terror and Heroism in Colonial Africa. Houghton Mifflin u. a., New York u. a. 1999, ISBN 0-333-76544-3.
 Martin Dugard: Auf nach Afrika! Stanley, Livingstone und die Suche nach den Quellen des Nils. Piper, München u. a. 2005, ISBN 3-492-24407-6 (Serie Piper).
 Joachim Fritz-Vannahme: Feder und Peitsche. In: Die Zeit, Nr. 19/2004, "Zeitläufte".
 Alan Gallop: Mr Stanley, I presume?: the life and explorations of Henry Morton Stanley. Sutton, Stroud 2004, ISBN 0-7509-3093-4.

Weblinks

 Zur Geschichte der Gumminutzung, mit ausführlichen Erläuterungen zum Kongo
 kongo-kinshasa.de deutschsprachige Seite zum Kongo
 Artikel zur Gründung der Kongokolonie
 Archiv Henry Morton Stanley, Königliches Museum für Zentralafrika
 Patric Seibel: Henry Morton Stanley – Ein Rassist und skrupelloser Entdecker, Deutschlandfunk Kultur

Einzelnachweise

Afrikaforscher
Autor
Entdecker (19. Jahrhundert)
Literatur (Englisch)
Literatur (19. Jahrhundert)
Literatur (20. Jahrhundert)
Reiseliteratur
Journalist (Vereinigtes Königreich)
Journalist (Vereinigte Staaten)
Belgische Kolonialgeschichte (Afrika)
Ehrendoktor der University of Oxford
Ehrendoktor der University of Cambridge
Ehrendoktor der University of Durham
Ehrendoktor der University of Edinburgh
Ehrenbürger von London
Knight Grand Cross des Order of the Bath
Abgeordneter des House of Commons (Vereinigtes Königreich)
Mitglied der Liberalen Unionisten
Politiker (19. Jahrhundert)
Politiker (20. Jahrhundert)
Waliser
Brite
US-Amerikaner
Geboren 1841
Gestorben 1904
Mann


We hope you are able to join us for Young Pastor's Time Out 2015! We believe that this event is a valuable retreat for young pastors in ministry. At this retreat we aim to provide ministry for the minister in both a personal and practical way, including spiritually refreshing sessions for all who attend. There will also be lots of time to relax, recharge and spend time with old and new friends. Our hope is that you will leave refreshed, connected, challenged, self-aware and refocused. Click here for Registration and Event Details.


Hi. I've been trying to publish a page on both desktop sitebuilder and online sitebuilder plus, but it's not uploading -- or at least it's not showing online. Any ideas why? Thank you in advance.
I cannot see any reason why your site wouldn't be publishing. Can you try going into the file manager in Sitebuilder Plus and publishing from there? If it doesn't work, it should at least give you an error message telling you why.
Which page are you trying to publish?
I'm not sure what the fellow did at the repair shop, but perhaps it has something to do with that fact that he downloaded a newer version of Internet Explorer. (Just a guess.) Anyway, I'm sorry to have bothered you. I was trying it all morning yesterday and couldn't figure out the problem. Thanks again for your reply.
Oh, I'm glad you got that resolved! I'm not sure what he might have done, but that builder does tend to become more incompatible the more a computer is updated, so that is possible.
No problem, it's not a bother. I'm here to help.
Many thanks, Elyzabeth. Hope you have a great weekend.
Thank you, I hope you have a great weekend as well.


Love stains on an organic kids dress! Lovely!
We make the Love Stain String Dress out of fibers, that are 100% organic and GOTS certified. The fabric feels supersoft on the skin, your kid will love the feel. The fabric is safe to wear and the colors are long-lasting. The Love Stain String Dress comes in a natural color tone with large dots in grey from our handpainted design. We use a rotation print method, that will last for a very long time. This string dress has a beautiful and simple cut. The dress falls loosely around the knees. It starts just below the arms and has two simple strings, that you can tie behind the neck. We like the simplicity of the Love Stain String Dress. Breezy around the shoulders, this dress is perfect for the warm summer days.


Tonight's episode of The Tonight Show took place in Puerto Rico. While out in the streets of old San Juan, Jimmy Fallon, Questlove and Black Thought linked up with Bad Bunny for a rousing street parade rendition of "MIA," accompanied by a tremendous crowd. Elsewhere in the episode, Fallon interviewed Lin-Manuel Miranda from the set of Hamilton regarding hurricane relief efforts, and Ozuna performed "En Mi Viejo San Juan" with Jose Feliciano. While that performance isn't yet online, watch the "MIA" performance above.


text:
February 19, 2020 by Graeme MacKay
Editorial Cartoon by Graeme MacKay, The Hamilton Spectator – Wednesday February 12, 2020
'We don't play games when people are sick': China won't release 'two Michaels' despite coronavirus help: experts
Ottawa shouldn't expect Beijing to do it any favours and free the "two Michaels" in return for medical co-operation fighting the new coronavirus, experts say.
China's ambassador to Canada hinted at that last week and Foreign Affairs Minister Francois-Philippe Champagne says he's used every medical discussion with China to raise the plight of the two men.
Champagne told reporters in Ethiopia on Sunday that he's had more access to his Chinese counterparts in recent weeks and he uses the occasions to push for the release of Michael Kovrig and Michael Spavor, who have been in Chinese prisons without charge since December 2018.
They were arrested in what is widely seen as retaliation for Canada's decision to arrest Huawei executive Meng Wanzhou on an extradition request from the United States.
David Mulroney, a former Canadian ambassador to China, says that while it is good for Champagne to keep pushing, Canada's assistance on the coronavirus simply isn't contingent on what China can do for Canada.
"Anything that opens up the channels of communication is a good thing, and we should use the conversation to raise all of our priorities," he said.
"We don't play games when people are sick, and we shouldn't allow China to play games with us. Freeing the Michaels isn't a favour or quid pro quo; it is what we expect of law-abiding states."
Bessma Momani, an international-affairs expert at the University of Waterloo, says China wants only one thing — Meng released — and so-called health diplomacy will not change that.
"I hope I'm wrong," she said.
"Why would Champagne say that? It's kind of raising hope. So, it makes you wonder," she said. "But at the same time, what would the Chinese get out of doing this? To them, Meng is a really important person … They don't want to be seen as giving in."
Meng is the daughter of Ren Zhengfei, the founder of Huawei.
Charles Burton, a former Canadian diplomat who has served in Beijing, said the Canadian efforts on the coronavirus might bear fruit.
"China is a gift giving culture. Any gift accepted creates reciprocal obligation in the recipient. So, I judge that China requesting medical aid from Canada could well lead to concessions in the negotiations over the release of Kovrig and Spavor," said Burton, of the Macdonald-Laurier Institute think-tank in Ottawa. (National Post)
Posted in: Canada, International	Tagged: 2020-06, Canada, China, Coronavirus, detainees, diplomacy, Michael Kovrig, Michael Spavor, Wuhan
← Tuesday February 11, 2020
Thursday February 13, 2020 →


I wonder if the right partner, or the right community, or the right something came into my life would that make me want to stay put or am I just by my very nature meant to roam. The longest I have stayed anywhere since leaving my parent's home in 1990 (boarding school!) was the four years I spent in university. It actually astounds me that I was so totally content at Carleton. But in some ways it's reassuring, that perhaps I'm not just always looking for something outside myself to provide happiness. Since those Northfield, MN days, I've maxed out at about two and a half years in New Haven, CT; the first location post-college.
The past few weeks were spent packing up what I decided it was worth storing for an indefinite period, selling and giving away the things that weren't, and arranging things such as providing my parents easy access to my assets in the event of an emergency. I still have quite a few things to get in order but things are pretty well organized for this totally life-changing move.