text:
Statins, Fibrates Lower Diabetic Retinopathy Risks in Diabetes
The use of lipid-lowering medication with fibrates, including fenofibrate (Lipidil, Abbott), and statins reduces not only the incidence of diabetic retinopathy in patients with type 2 diabetes but also the need for treatment in those who already have the condition, indicates a real-world Japanese study.
Ryo Kawasaki, MD, MPH, PhD, Department of Vision Informatics (Topcon), Osaka University Graduate School of Medicine, Japan, and colleagues retrospectively analyzed health claims data on almost 85,000 patients with type 2 diabetes.
The results, published in the October issue of Diabetes, Obesity and Metabolism, show that the incidence of diabetic retinopathy was reduced by around 23% with the use of lipid-lowering medication, and fibrates and statins were similarly effective.
And the need for any diabetic retinopathy treatment among patients with type 2 diabetes who already had the complication was reduced by 35% with lipid-lowering medication, and the need for laser photocoagulation and vitrectomy was reduced by 35% and 52%, respectively.
The results follow data from the ACCORD study, which showed that combining fenofibrate with a statin reduced the rate of progression of diabetic retinopathy, and an analysis of the FIELD study indicated that fenofibrate reduced the need for laser treatment of diabetic retinopathy (Lancet. 2007;370:1687-1697).
Indeed, in 2013 fenofibrate was given its first, and to date only, approval in a major market — Australia — to slow the progression of existing diabetic retinopathy in people with type 2 diabetes.
Kawasaki noted, however, that although "fenofibrate or fenofibrate on top of statins have been shown to reduce risk of progression, it has not been well elucidated if lipid-lowering medication is beneficial to the incidence of diabetic retinopathy."
He told Medscape Medical News: "Our study is suggesting that lipid-lowering medication is beneficial for both the incidence and progression of diabetic retinopathy."
However, he added that "this is an observational study and limited to health claims data without clinical quantitative variables such as glucose level or severity of retinopathy," and he called for more studies on this "promising topic."
Clinical Trial Needed, but Challenging, for Fibrates in Diabetic Retinopathy
Kawasaki underlined that it is not clear from the current study whether the findings can be ascribed to the specific effect of fenofibrate, or fibrates in general, as "we did not separate fenofibrate from other types of fibrates, mainly due to a relatively small number of patients."
He nevertheless said that given that fibrates, or fenofibrate in particular, "might have pleiotropic effects in addition to the lipid-lowering effect, we are expecting that this area of research becomes more active."
He pointed to the recent approval in Japan of pemafibrate (Parmodia, Kowa Company), which is a more selective peroxisome proliferator-activated receptor alpha (PPAR-α) modulator than conventional fibrates.
"This might have potential benefit for diabetic retinopathy," he said, "for which we believe a clinical trial is warranted."
Kawasaki added that the prevention of diabetic retinopathy with lipid-lowering medication is "quite promising in theory and there is supportive clinical evidence; however, it is also challenging to conduct a new trial to show the beneficial effect of statins/fibrates, given most patients with diabetes are already on those medications."
Lipid-Lowering Reduces Incidence of Diabetic Retinopathy in Real-World
He and his co-authors say that, although there appears to have been a decline in both the incidence and prevalence of diabetic retinopathy in developed countries, and the effective management of glucose levels and hypertension can prevent or delay it, "a residual risk" remains.
This is purported associated with dyslipidemia, specifically high cholesterol and triglyceride levels, although they note the evidence for this association is "inconsistent" and not as strong as that for diabetic kidney disease.
And as data on this is mainly from clinical trials, they set out to determine whether lipid-lowering medication reduces the risk of diabetic retinopathy and the need for treatment in a more real-world setting.
They gathered information from the health claims database of the Japan Medical Data Center, Tokyo, on adults with a diagnosis of type 2 diabetes or unspecified diabetes and a prescription for a glucose-lowering medication from 2005 to 2017.
They divided the claims into a baseline period of 2005 to 2013 and a follow-up period of 2014 to 2017.
The participants were divided into two cohorts: one that was diabetic retinopathy-free during the baseline period to determine the incidence of diabetic retinopathy during the follow-up period, and the second which consisted of individuals diagnosed with diabetic retinopathy during the baseline period. The latter group was recruited to determine the incidence of diabetic macular edema and the use of diabetic retinopathy-related treatments during the follow-up period.
The team reports that 69,070 individuals were included in the first cohort.
Of these, 20.9% were prescribed standard statins, such as simvastatin and pravastatin, and 79.1% "strong" statins, which included atorvastatin and rosuvastatin. In addition, 54.4% were prescribed bezafibrate and 45.5% fenofibrate.
Patients given lipid-lowering medication were significantly more likely to be women and older, have a longer duration of diabetes and more comorbidities, and be treated with insulin, antihypertensives, and anticoagulants than those not prescribed the medications (P < .001 for all).
During the 3-year follow-up, 7110 individuals developed diabetic retinopathy.
Lipid-lowering medication was associated with a significantly reduced incidence of diabetic retinopathy, with 7.4% of patients treated with the drugs developing the complication versus 11.4% of patients not treated (P < .001).
Logistic regression analysis revealed that lipid-lowering medication was associated with a significantly reduced risk of developing diabetic retinopathy, at an odds ratio (OR) of 0.77 (P < .001).
Both statins and fibrates were separately and independently associated with a reduced risk of diabetic retinopathy, at weighted ORs of 0.79 (P < .001) and 0.78 (P < .003), respectively.
Likelihood of Needing Treatment If Patients Had Diabetic Retinopathy
For the second cohort, 15,738 individuals were selected from the claims database who had diabetic retinopathy at baseline. Of those, 347 developed diabetic macular edema within 3 years, for a rate of 1.2% of patients treated with lipid-lowering medication vs 2.7% of those not treated (P < .001).
Lipid-lowering medication was linked to a significant reduction in the risk of developing diabetic macular edema during follow-up, at an OR of 0.41 (P < .001), as was statin use (OR, 0.38; P < .001) and fibrate use (OR, 0.27; P = .04) individually.
Patients with diabetic retinopathy given lipid-lowering medication were also significantly less likely than those not given the drugs to undergo any diabetic retinopathy-related treatment in general (P < .001), and laser photocoagulation (P < .001) and vitrectomy (P = .007) in particular.
Lipid-lowering medication overall was associated with a significantly reduced risk of receiving treatment for diabetic retinopathy, at an OR of 0.65 (P = .002), as were statins individually (OR, 0.62; P = .001) and fibrates (OR, 0.41; P = .018).
Although lipid-lowering medication was, overall, associated with a reduced risk of laser photocoagulation, at an OR of 0.65 (P = .013), only statin use was, separately, associated with a significant risk reduction (OR, 0.56; P = .04).
A similar pattern was seen for vitrectomy.
Noting that the results could be affected by confounding factors because of the nature of the data source, the team says: "These findings were consistent with the results of clinical trials in patients with diabetic retinopathy who required diabetic retinopathy treatment."
"Our observation further expanded the possibility that lipid-lowering medication can reduce the risk of developing diabetic retinopathy and reduce the need for diabetic retinopathy-related treatment in a relatively short duration of diabetes."
The study was supported by research grants provided by Novartis Pharma and Pfizer, Japan. The authors have reported no relevant financial relationships.
Diabetes Obes Metab. 2018;20:2351-2360. Abstract
For more diabetes and endocrinology news, follow us on Twitter and on Facebook.
Medscape Medical News © 2018 WebMD, LLC
Send comments and news tips to news@medscape.net.
Cite this: Statins, Fibrates Lower Diabetic Retinopathy Risks in Diabetes - Medscape - Sep 28, 2018.
Freelance journalist, Medscape
Disclosure: Liam Davenport has disclosed no relevant financial relationships.
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text:
other name آبادان
country Iran
Altitude 3 a.s.l.
coordinates 30° 22.2' N 48° 15.0' E
Weather Iran
Ābādān
Climate Abadan
Dec.hidden December 80 20 10
Jan. January 45 18 9
Feb. February 10 21 10
Mar. March 25 26 14
Apr. April 12 32 19
May May 2 40 25
Jun. June 13 45 28
Jul. July 0 46 29
Aug. August 0 46 29
Sep. September 0 43 24
Oct. October 2 36 20
Nov. November 14 27 14
Dec. December 80 20 10
Jan.hidden January 45 18 9
For the month of January, average values for station "Abadan" were calculated from climate data measured between the years 1994 and 2005.
For the month of February, average values for station "Abadan" were calculated from climate data measured between the years 1994 and 2005.
For the month of March, average values for station "Abadan" were calculated from climate data measured between the years 1994 and 2005.
For the month of April, average values for station "Abadan" were calculated from climate data measured between the years 1994 and 2005.
For the month of May, average values for station "Abadan" were calculated from climate data measured between the years 1994 and 2005.
For the month of June, average values for station "Abadan" were calculated from climate data measured between the years 1994 and 2005.
For the month of July, average values for station "Abadan" were calculated from climate data measured between the years 1994 and 2005.
For the month of August, average values for station "Abadan" were calculated from climate data measured between the years 1994 and 2005.
For the month of September, average values for station "Abadan" were calculated from climate data measured between the years 1994 and 2005.
For the month of October, average values for station "Abadan" were calculated from climate data measured between the years 1994 and 2005.
For the month of November, average values for station "Abadan" were calculated from climate data measured between the years 1994 and 2005.
For the month of December, average values for station "Abadan" were calculated from climate data measured between the years 1994 and 2005.
Climate Ahwaz
Climate Kuwait

redpajama_set_name: RedPajamaCommonCrawl


text:
Easy to run examples of heavy technologies like Java EE, Spring etc
1

redpajama_set_name: RedPajamaGithub


Product prices and availability are accurate as of 2019-04-25 22:42:24 UTC and are subject to change. Any price and availability information displayed on http://www.amazon.com/ at the time of purchase will apply to the purchase of this product.
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Enterprise users of SaaS applications, both in IT and in the line of business, are fans because of the lower fixed infrastructure costs; faster and simpler deployments; and relief from constant managing, updating and patching of apps. Software is often more reliable, more up-to-date, and more directly accessible for users, without going through IT.
Software vendors are fans of SaaS for all those reasons, as well, plus benefits including shortened sales cycles; faster upgrades and licensing changes; and a reliable, steady and predictable source of recurring income.
Security and data management/control are the most frequent topics of focus for IT organizations reluctant to move mission-critical apps and their data to the cloud. A recent survey conducted by QuinStreet Enterprise confirms that these two areas of concern continue to be sensitive, as only 27 percent of enterprise finance/accounting apps are delivered through the cloud, and only 32 percent of human resources apps are delivered in that manner. Less mature apps, like mobile device management or Big Data analytics apps, are showing much higher levels of cloud usage.
Cloud delivery of these enterprise applications is the subject of a live Google Hangout streaming on Enterprise Apps Today at 1:30 pm ET on Feb. 5. QuinStreet Enterprise editors from Enterprise Apps Today, eWEEK, CIO Insight, Baseline Mag and Datamation will share their perspectives and common-sense advice on application management.


text:
Q: Mabook Pro: replace with display assembly from later model possible? Can the display assembly in a MacBook Pro 15" late 2008 ( MacBookPro5,1) be replaced with a display assembly from a later model with identical Model Number A1286 and size (15.4")?
The APN for the MacBookPro5,1 is 661-4837 or 661-5091.
Later A1286 models have partly identical descriptions of the assembly in Mactracker, but have different APNs. Example (that I have an offer for): the MacBookPro8,2 came with assemblies 661-5847, 661-5849 (hi-res, anti-glare), or 661-5848 (hi-res, glossy).

A: im not a mac guru or certified apple tech etc. but
i was trying to do pretty much do the same thing with 15in mb pro a1211 (model 2,1)  not the exact same thing, which in the import honda world as doing a frankenstein build, mine was not display but logic board. which i still have yet to start on it. i was wanting to swap  my logic board (because i at time thought or was getting told that my logic board died,) for newer faster version,
  is able to be installed than just buy the original board as the prices on just the boards are pretty similar. to each other.   the major problem i kept having was that the people who own and use apple/mac products, share the same principles in rergards to apple products, much like saab, and porsche enthusiasts have about their cars, which its taboo, or not taboo, ill say it this way, a 20 year old porsche thats not in great shape  and needs repairs etc  is easier to sell and will yeild a higher selling price than the same year model porsche  that lets say has 40000 in engine and appreance type modifications    mainly the exterior styling body kits are the major factor.  same with apple fans, they buy it, then they dont get another till the other is in no way useable anymore. and up to the last model releases that came out uptil jobs died  you never had the need for cannibalisation of prodcuts to repair anothe.
anyway  after many weeks of surfing the web, and a buddy who was an actual apple store apple genius tech.
to do a frankenstein build,  you generally are constrained to the products within that model/version release family ie  like mine   im a model 2,1  so pretty much i could only interchange parts that were from that model line,  thered are exceptions,  but as long as the connecttions match,  and the programing code is same uyou could do it,
Everymac.com is an amazing resource for all things mac apple, macmall, etc,and ive also come across the PROPERIETARY apple repair/service manuals in pdf form that is free to download  may not get an authentically free download right off the bat but most times regardless of what type of manual it is   ive found a true free download at most by the 4th scfreen of web results
so hope that helps

redpajama_set_name: RedPajamaStackExchange


text:
BAP1 hereditary cancer predisposition syndrome: a case report and review of literature
Sonja Klebe1,
Jack Driml1,
Masaki Nasu2,
Sandra Pastorino2,
Amirmasoud Zangiabadi3,
Douglas Henderson1 &
Michele Carbone2
A 72-year-old woman was diagnosed with uveal melanoma, peritoneal mesothelioma and a primary biliary tract adenocarcinoma. She had a strong family history of mesothelioma as well as other malignancies including renal cell carcinoma. The recently described BAP1 hereditary cancer predisposition syndrome was suspected, but immunohistochemical labeling was not conclusive. Genetic testing confirmed a novel and unusual germline mutation in the ubiquitin hydrolase domain of the BAP1 gene (p.Tyr173Cys) and the patient was diagnosed with the BAP1 hereditary cancer predisposition syndrome. This case demonstrates the importance of clinically recognizing this rare syndrome and its manifestations, some which are still being characterized. It also highlights the importance of genetic testing in cases where there is a high clinical suspicion, even when screening tests, such as immunohistochemistry, in this case, are inconclusive. The diagnosis of a germline BAP1 mutation may have important implications for both the patient and their families with regards to further genetic testing and active surveillance programs. Further research is needed to fully understand the extent and clinical implications of this rare cancer syndrome.
A number of rare cancers, in particular mesothelioma and uveal melanoma have been shown to occur together, being noted as early as the 1970s. Furthermore there have been cases of strong familial clustering of malignant mesothelioma, often with limited asbestos exposure, a known carcinogen recognized as causing mesothelioma. Genetic studies of these families subsequently lead to the discovery of germline mutations in BAP1 and the recognition of a new cancer predisposition syndrome. At present this syndrome has been shown to predispose to the development of uveal melanoma, malignant mesothelioma, cutaneous melanoma and renal cell carcinoma, but has also been implicated in the development of other malignancies. Here we report the first case of this new cancer syndrome in Australia, leading to the development of 3 distinct malignancies.
A 72-year-old, previously well, woman was found to have left ocular uveal melanoma on ophthalmology review (Fig. 1). She had previously been noted to have 'freckles' on her left retina. At the time of diagnosis the patient was asymptomatic, suffered no visual impairment and declined further investigation, radiotherapy or enucleation. A one-year follow up showed growth of the uveal melanoma with staging undertaken prior to intended radiotherapy. An abdominal CT scan demonstrated a lesion within segments 4 and 7 of her liver (Fig. 1). A Further PET scan showed a focal area of FDG avidity within segment 4 but no increased FDG uptake in liver segment 7,
Imaging of patient with germline BAP1 mutation. a. Retinal examination revealed a melanocytic tumor with irregular margins involving the majority of the retina. b. CT of the abdomen prior to surgery identified a 32 mm lobulated lesion in segment 4B of the liver as indicated by the arrow
A diagnostic laparoscopy was performed for the liver lesions of unknown origin. Intraoperatively, no free intraperitoneal fluid was seen but numerous peritoneal nodules were noted on the diaphragmatic and peritoneal surfaces, particularly in the right upper quadrant. There was no obvious omental disease. These peritoneal nodules along with the liver lesion were biopsied. The liver biopsy showed focally necrotic poorly differentiated adenocarcinoma. Immunohistochemical labeling was in keeping with cholangiocarcinoma and in the absence of a primary site in the extrahepatic biliary system or upper gastrointestinal tract the lesion was considered to likely represent a primary intrahepatic cholangiocarcinoma. The lesion did not label for any immunohistochemical markers for melanoma. The peritoneal biopsy showed nodular proliferations of mesothelial cells with infiltration into the submesothelial adipose tissue indicative of malignant mesothelioma of epithelial type. Immunohistochemistry was positive for mesothelial markers and negative for carcinoma markers.
Pedigree of the patient's family with a BAP1 germline mutation. Black Squares indicate a diagnosis of malignant mesothelioma. Arrow indicates the presence of BAP1 mutation as determined by sequencing studies. Two of the patient's children passed away with renal cell carcinoma (RCC) and acute lymphocytic leukaemia (ALL)
The patient's father and brother had both died of malignant mesothelioma (Fig. 2) having had occupational exposure to asbestos. The patient herself had no occupational exposure to asbestos but may have had ongoing household exposure since the 1970s. Her past medical history was unremarkable besides beta thalassemia minor and a previous hysterectomy for benign disease. The patient was of Greek descent. She was a non-smoker and only occasionally drank alcohol. The patient had four children, and two of these had passed away with renal cell carcinoma and acute lymphocytic leukaemia at ages 41 and 17 respectively (Fig. 2).
Elective surgical resection was deemed appropriate for the patient's primary liver mass. A CT prior to resection demonstrated no change in the liver lesion and no evidence of extrahepatic spread. Intraoperatively, a firm porta hepatic node was identified with frozen sectioning confirming metastatic adenocarcinoma. Fine needle aspiration of the segment 7 also showed adenocarcinoma and in view of positive intra- and extrahepatic disease the liver resection was abandoned. A strip of peritoneum was also removed which again demonstrated malignant mesothelioma.
In light of her uveal melanoma and malignant mesothelioma, combined with her family history of mesothelioma it was suspected that the patient might have BAP1 hereditary cancer predisposition syndrome. Testing for BAP1 mutations by immunohistochemistry showed loss of nuclear BAP1 labeling in the primary biliary tract adenocarcinoma, but nuclear labeling for BAP1 was retained in the malignant mesothelioma (Fig. 3 ). No biopsies were taken from the uveal melanoma. Germline DNA sequencing was performed and revealed the patient to carry a germline missense mutation in the catalytic domain (g.52441252A > G, p.Tyr173Cys) located in exon 7 of the BAP1 gene (Fig. 4). This mutation is predicted to generate a non-functional full-length protein, due to impairment of its ubiquitin hydrolase activity.
Histological findings of patient with BAP1 germline mutation a. Liver biopsy demonstrating focally necrotic poorly differentiated intrahepatic adenocarcinoma (Hemosiderin and Eosin, original magnification 250×). b. Immunohistochemical labeling for BAP1 protein in the cholangiocarcinoma, showing loss of nuclear staining. (Santa Cruz BAP1 monoclonal antibody (sc-28383) 1: 200. Dako dual system detection, original magnification 400×) c. Peritoneal biopsy demonstrating malignant mesothelioma of epithelial type with invasion into the submesothelial adipose tissue. (Hemosiderin and Eosin, original magnification 250×). d. Immunohistochemical labeling for BAP1 for peritoneal biopsy showing retained BAP1 nuclear staining in malignant peritoneal mesothelioma (Tissue preparation s above, original magnification 400×)
Germline BAP1 missense mutation found in this patient. Germline DNA was extracted from the patient's blood and analysed by Sanger sequencing. DNA amplification and sequencing were performed as previously described (Forward primer: GGAGTTGGCCAAGGCCCATAATAGC; reverse primer: CCTGGATACTCTCTGTCCCTCCCAAAG) [1]. Electropherogram shows BAP1 missense mutation (g.52441252A > G) within exon 7. This mutation produces an amino-acid sequence switch from tyrosine to cysteine in the ubiquitin hydrolase domain (UCH), and indicated by the diagram
Further CT surveillance of the patient demonstrated an enlarging liver mass, development of new liver lesions and increasing portacaval lymph nodes. No other distant sites of metastasis where identified on CT. The patient become symptomatic 23 months after the diagnosis of cholangiocarcinoma and mesothelioma and was commenced on palliative chemotherapy. She passed away 31 months after diagnosis of cholangiocarcinoma and mesothelioma due to progression of her intraabdominal malignancies.
BAP1 hereditary cancer predisposition syndrome was first described in 2011 based on investigations of two American families [1]. It is a syndrome that describes a predisposition to the development of several malignancies, in particular uveal melanoma and malignant mesothelioma as well as cutaneous melanomas, basal cell carcinomas and renal cell carcinoma [2-7]. Other cancers have been reported in families suffering germline mutations but no direct correlations have yet been established. In a review of 76 patients with a BAP1 germline mutation, 53 patients had developed at least one malignancy with 13 developing at least two. Those who had not yet developed a malignancy were all aged less than 55 [8]. This study highlights the strong link between germline BAP1 mutations and carcinogenesis. Here, we reported a case involving an individual with a germline BAP1 mutation who was diagnosed with 3 distinct malignancies in short succession, an event that appears uncommon even for individuals carrying a germline BAP1 mutation.
BAP1 (BRCA1-associated protein 1) is a nuclear protein encoded by the tumour suppressor gene located on chromosome 3p21.1 [9]. It is a deubiquitinating enzyme, usually part of a protein complex, and has been implicated in a number of different cellular processes including chromatin remodeling, cell cycle progression, cell differentiation and DNA damage responses [4]. The understanding of BAP1's role in cellular processes and subsequent carcinogenesis has increased in recent years however the function of BAP1 is still being fully characterized, in particular its contribution to carcinogenesis. Both germline and somatic mutations have been implicated in tumour progression [1, 3, 9]. BAP1 mutations may result in proteins that lack the nuclear localization sequence, or may affect its deubiquitinase activity [1, 4, 9]. It is not fully known why germline mutations may predispose to the development of certain cancers over others; most likely cell-type specific functions as well as gene-environment interactions play an important role.
The BAP1 germline alteration identified in our patient was a missense mutation at the active site of its ubiquitin hydrolase domain. Similar missense mutations were found in uveal melanoma (p.Ser172Arg) [10] and pleural biphasic mesothelioma (p.Tyr173Ser) tissue [11]. While the role of this specific mutation is not known yet, the critical role of the deubiquitinating.activity of BAP1 in its tumour suppressor activities have been well established [12, 8] The tumor suppressor function of BAP1 has been shown to require its nuclear localization. Therefore absence of BAP1 nuclear staining and/or presence of cytoplasmic BAP1 indicate the presence of an abnormal BAP1 protein. Both N-terminus BAP1 mutations and C-terminus mutations lead to lack of BAP1 nuclear labeling due to either lack of the nuclear localization signal, or to lack of deubiquitinase activity, as autodeubiquition is required for nuclear transport of BAP1 protein [13]. This has been confirmed in a comprehensive study showing that all BAP1 abnormalities found in mesothelioma to date are always associated with absence of BAP1 nuclear staining and/or presence of cytoplasmic BAP1 staining [14].
The complete loss of BAP1 nuclear staining observed in our primary biliary tract adenocarcinoma is likely due to LOH at somatic level, while the mesothelioma tissue seems to have preserved the other BAP1 allele. One could argue that the fact that mesothelioma developed even in absence of LOH further confirms the deleteriousness of the Tyr 173 mutation. Definitive sequencing was not performed on tumour samples, which were largely exhausted by diagnostic tests. Loss of nuclear BAP1 staining on immunohistochemistry was thought to be an accessible and reliable test of BAP1 mutations, including germline [15, 8] and has been used for prognostication in mesothelioma [16, 17]. However the presence of retained nuclear staining in this case highlights the need for clinician awareness of BAP1 germline mutations and for definitive germline genetic testing.
With regards to specific cancers, germline BAP1 mutations have been shown to play a role in a small number (3-4 %) of uveal melanomas [18, 19]. Uveal melanoma is a rare ocular cancer with variable outcome, depending on molecular and clinical characteristics [20]. BAP1 mutations have been implicated in metastatic ability. A germline mutation was found in 4 out of 50 metastatic uveal melanomas and was not identified in a further 50 non-metastatic tumours [18]. Sporadic BAP1 mutations have also been found in 84 % of metastasizing uveal melanomas [10]. Loss of BAP1 both germline and sporadic appears to lead to a more aggressive tumour phenotype in uveal melanoma.
Malignant mesothelioma is another rare cancer that has been associated with BAP1 germline mutations [4]. It is an aggressive cancer with limited treatment options often due to late diagnosis. Both germline and sporadic BAP1 mutations has been shown to play a role in malignant mesothelioma. BAP1 appears to be sporadically mutated in a significant portion ~60 % of malignant mesotheliomas [11, 1, 14, 9]. Germline mutations make up much smaller proportion of cancers. A recent study compared the clinical characteristics of 23 mesotheliomas that occurred in carriers of germline BAP1 mutations to 10,556 sporadic mesotheliomas [21]. These patients tended to have a family history of malignant mesothelioma with limited asbestos exposure. Tumors that occur in a setting of germline BAP1 mutations are much less aggressive than their somatic counterparts and are associated with a significant improved mean survival of 5 years compared to 1 year with sporadic malignant mesothelioma [21]. This improved survival is observed in the patient reported here. Loss of nuclear labeling for BAP1 in the absence of known germline mutations has been associated with a less dramatic improvement in prognosis [17, 16]. Germline mutations also had a higher incidence of peritoneal disease (as in our patient) where in sporadic tumours pleural disease predominates. The recent discovery of BAP1 involvement has given much needed insight into the pathogenesis of mesothelioma and in particular has added valuable prognostic information [16, 17].
Germline BAP1 mutations have cutaneous manifestations that include basal cell carcinomas, malignant melanoma and the recently described melanocytic-BAP1 mutated atypical intradermal tumour (MBAIT) [2, 8, 6, 5, 7]. MBAITs are pink to tan benign skin tumours around 0.2 – 1 cm in diameter that macroscopically resembles dermal nevi but are clinically, histologically, and genetically distinct. They have been shown to have high levels of mutated BRAF which can distinguish them from benign Spitz naevi [15]. They can appear as early as the second decade with an individual developing multiple lesions over their lifetime. They appear clinically stable with a low malignant potential but there are reports of progression to malignant melanoma. The number of cutaneous melanoma is still low in these families despite significant number of MBAITs. Bi-allelic loss of BAP1 in itself along with a BRAF mutation is not sufficient for melanoma formation [2]. It has been suggested that MBAITs may be used to screen individuals for germline BAP1 mutations; 19 out of 35 individuals with a BAP1 mutation were found to have one or more lesion [4]. Furthermore, MBAITs occur earlier than other associated malignancies, allowing for identification of at risk individuals, genetic testing and implementation of surveillance protocols.
Renal cell carcinoma is the most recent tumour associated with BAP1 germline mutations. The majority of renal cancers are sporadic however a small proportion (2-4 %) is familial, the majority of these due to Von Hippel Lindau syndrome [22]. A much smaller component can be attributed to germline BAP1 mutations [3, 23]. It should be noted that our patient's son died of renal cell carcinoma. Sporadic BAP1 mutations have also been associated with a more aggressive form of cancer [24] however it appears germline mutations may have different consequences [3]. Further research is needed to understand the contributing and prognostic role of BAP1 in renal cell carcinoma.
Other cancers including meningioma, lung, ovarian, pancreatic and breast cancers have been found in families that harbor BAP1 germline mutations [4]. However it is unclear whether germline BAP1 mutations directly predispose to the development of these tumours.
Our patient was diagnosed with a primary biliary tract cancer. There are reports of individuals with BAP1 mutations developing primary biliary tract cancers but no definitive predisposition has been attributed [4, 21]. Somatic BAP1 mutations are relatively frequent in cholangiocarcinoma [25-28]. Our own immunohistochemistry showed complete loss of BAP1 nuclear staining in the primary biliary tract adenocarcinoma. This indicates that secondary sporadic mutations had occurred in the adenocarcinoma, resulting in loss of protein translocation (Fig. 3). Further epidemiological studies are needed to confirm whether primary biliary tract tumours, contribute to the spectrum of BAP1 hereditary cancer predisposition syndrome.
The recent discovery of this rare cancer predisposition syndrome has a number of clinical implications. Firstly, it is important to identify these patients and their families through genetic testing. It would be advisable to perform genetic testing on patients diagnosed with uveal melanoma and mesothelioma, those with mesothelioma who have a strong family history of the disease and as well as those found to have MBAITs. The indication of offering BAP1 genetic testing for other familial cancer associations is less clear, considering the rarity of this syndrome. Those who are confirmed to carry a BAP1 mutation will then need appropriate genetic counseling for themselves and their families. Some authors advocate affected family members should undergo annual total skin checks for MBAITs as well as ocular examination [8]. As the full extent of this syndrome is not yet known it is unclear what the appropriate surveillance programs should be. Early detection and management of malignant mesothelioma and other related malignancies may improve survival.
BAP1 mutations have been described in some US and European families with a very high incidence of cancer and they are transmitted in a Mendelian fashion (i.e., about 50 % of offspring inherit the mutation). So far all of the family members that inherited this mutation have developed one and often several cancers by age 65 (18). Characteristically, when malignancies occur in a setting of germline BAP1 mutations they are less aggressive and patients live significantly longer compared to patients with the same types of tumors occurring in a sporadic setting [21]. Here we describe the first Australian family affected by the BAP1 cancer syndrome. Our findings reveal that this cancer syndrome is ubiquitous and it is not restricted to the US and Europe. Clearly identification of these patients is critical to provide them correct medical advice and genetic counseling.
Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2011;43(10):1022–5. doi:10.1038/ng.912.
Wiesner T, Obenauf AC, Murali R, Fried I, Griewank KG, Ulz P, et al. Germline mutations in BAP1 predispose to melanocytic tumors. Nat Genet. 2011;43(10):1018–21. doi:10.1038/ng.910.
Popova T, Hebert L, Jacquemin V, Gad S, Caux-Moncoutier V, Dubois-d'Enghien C, et al. Germline BAP1 mutations predispose to renal cell carcinomas. Am J Hum Genet. 2013;92(6):974–80. doi:10.1016/j.ajhg.2013.04.012.
Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. BAP1 and cancer. Nat Rev Cancer. 2013;13(3):153–9.
Mochel MC, Piris A, Nose V, Hoang MP. Loss of BAP1 Expression in Basal Cell Carcinomas in Patients With Germline BAP1 Mutations. Am J Clin Pathol. 2015;143(6):901–4. doi:10.1309/AJCPG8LFJC0DHDQT.
Wadt KA, Aoude LG, Johansson P, Solinas A, Pritchard A, Crainic O, et al. A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma. Clin Genet. 2014. doi:10.1111/cge.12501.
de la Fouchardiere A, Cabaret O, Savin L, Combemale P, Schvartz H, Penet C, et al. Germline BAP1 mutations predispose also to multiple basal cell carcinomas. Clin Genet. 2014. doi:10.1111/cge.12472.
Carbone M, Ferris LK, Baumann F, Napolitano A, Lum CA, Flores EG, et al. BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs. J Transl Med. 2012;10:179. doi:10.1186/1479-5876-10-179.
Bott M, Brevet M, Taylor BS, Shimizu S, Ito T, Wang L, et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet. 2011;43(7):668–72. doi:10.1038/ng.855.
Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA, et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science (New York, NY). 2010;330(6009):1410–3. doi:10.1126/science.1194472.
Yoshikawa Y, Sato A, Tsujimura T, Emi M, Morinaga T, Fukuoka K, et al. Frequent inactivation of the BAP1 gene in epithelioid-type malignant mesothelioma. Cancer Sci. 2012;103(5):868–74. doi:10.1111/j.1349-7006.2012.02223.x.
Ventii KH, Devi NS, Friedrich KL, Chernova TA, Tighiouart M, Van Meir EG, et al. BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization. Cancer Res. 2008;68(17):6953–62. doi:10.1158/0008-5472.can-08-0365.
Mashtalir N, Daou S, Barbour H, Sen NN, Gagnon J, Hammond-Martel I, et al. Autodeubiquitination protects the tumor suppressor BAP1 from cytoplasmic sequestration mediated by the atypical ubiquitin ligase UBE2O. Mol Cell. 2014;54(3):392–406. doi:10.1016/j.molcel.2014.03.002.
Nasu M, Emi M, Pastorino S, Tanji M, Powers A, Luk H, et al. High Incidence of Somatic BAP1 alterations in sporadic malignant mesothelioma. J Thorac Oncol. 2015;10(4):565–76. doi:10.1097/jto.0000000000000471.
Wiesner T, Murali R, Fried I, Cerroni L, Busam K, Kutzner H, et al. A distinct subset of Atypical Spitz Tumors is characterized by BRAF mutation and loss of BAP1 expression. Am J Surg Pathol. 2012;36(6):818–30. doi:10.1097/PAS.0b013e3182498be5.
PubMed Central PubMed Article Google Scholar
Farzin M, Toon CW, Clarkson A, Sioson L, Watson N, Andrici J, et al. Loss of expression of BAP1 predicts longer survival in mesothelioma. Pathology. 2015;47(4):302–7. doi:10.1097/PAT.0000000000000250.
Arzt L, Quehenberger F, Halbwedl I, Mairinger T, Popper HH. BAP1 protein is a progression factor in malignant pleural mesothelioma. Pathol Oncol Res. 2014;20(1):145–51. doi:10.1007/s12253-013-9677-2.
Njauw CN, Kim I, Piris A, Gabree M, Taylor M, Lane AM, et al. Germline BAP1 inactivation is preferentially associated with metastatic ocular melanoma and cutaneous-ocular melanoma families. PLoS One. 2012;7(4), e35295. doi:10.1371/journal.pone.0035295.
Aoude LG, Vajdic CM, Kricker A, Armstrong B, Hayward NK. Prevalence of germline BAP1 mutation in a population-based sample of uveal melanoma cases. Pigm Cell Melanoma Res. 2013;26(2):278–9. doi:10.1111/pcmr.12046.
Coupland SE, Lake SL, Zeschnigk M, Damato BE. Molecular pathology of uveal melanoma. Eye (Lond). 2013;27(2):230–42. doi:10.1038/eye.2012.255.
Baumann F, Flores E, Napolitano A, Kanodia S, Taioli E, Pass H, et al. Mesothelioma patients with germline BAP1 mutations have 7-fold improved long-term survival. Carcinogenesis. 2015;36(1):76–81. doi:10.1093/carcin/bgu227.
Axwijk PH, Kluijt I, De Jong D, Gille H, Teertstra J, Horenblas S. Hereditary causes of kidney tumours. Eur J Clin Investig. 2010;40(5):433–9. doi:10.1111/j.1365-2362.2010.02270.x.
Pilarski R, Cebulla CM, Massengill JB, Rai K, Rich T, Strong L, et al. Expanding the clinical phenotype of hereditary BAP1 cancer predisposition syndrome, reporting three new cases. Gene Chromosome Canc. 2014;53(2):177–82. doi:10.1002/gcc.22129.
Pena-Llopis S, Vega-Rubin-de-Celis S, Liao A, Leng N, Pavia-Jimenez A, Wang S, et al. BAP1 loss defines a new class of renal cell carcinoma. Nat Genet. 2012;44(7):751–9. doi:10.1038/ng.2323.
Simbolo M, Fassan M, Ruzzenente A, Mafficini A, Wood LD, Corbo V, et al. Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups. Oncotarget. 2014;5(9):2839–52.
Jiao Y, Pawlik TM, Anders RA, Selaru FM, Streppel MM, Lucas DJ, et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat Genet. 2013;45(12):1470–3. doi:10.1038/ng.2813.
Churi CR, Shroff R, Wang Y, Rashid A, Kang HC, Weatherly J, et al. Mutation profiling in cholangiocarcinoma: prognostic and therapeutic implications. PLoS One. 2014;9(12), e115383. doi:10.1371/journal.pone.0115383.
Chan-On W, Nairismagi ML, Ong CK, Lim WK, Dima S, Pairojkul C, et al. Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat Genet. 2013;45(12):1474–8. doi:10.1038/ng.2806.
We gratefully acknowledge Dr Brian Stein and Dr James Muecke who contributed patient information and the image of the ocular melanoma. Kim Griggs performed the immunohistochemistry. Supported in part by the University of Hawaii Foundation, which received unrestricted donations to support mesothelioma research from Honeywell International Inc., to MC. Supported in part by the Australian Respiratory and Sleep Medicine Institute, to SK.
Department of Anatomical Pathology, Flinders Medical Centre and Flinders University, Bedford Park, SA 5042, UK
Sonja Klebe, Jack Driml & Douglas Henderson
University of Hawaii Cancer Center, 701 Ilalo Street, Bldg A-4R, Rm 450, Honolulu, HI, 96813, USA
Masaki Nasu, Sandra Pastorino & Michele Carbone
Department of Respiratory and Sleep Medicine, Flinders Medical Centre, Bedford Park, SA 5042, UK
Amirmasoud Zangiabadi
Sonja Klebe
Jack Driml
Masaki Nasu
Sandra Pastorino
Douglas Henderson
Michele Carbone
Correspondence to Sonja Klebe.
M. Carbone has pending patent applications on BAP1, and provides consultation for mesothelioma diagnosis. SK and DH provide advice on mesothelioma diagnosis in medicolegal cases.
SK and DH were involved in the diagnosis, immunohistochemical testing and critical interpretations. SK and JD reviewed the literature and wrote the paper. AZ interviewed the patient and obtained consent. MN, SP and MC performed the genetic testing and analysis and carried out critical interpretations. All authors read and approved the final manuscript.
Klebe, S., Driml, J., Nasu, M. et al. BAP1 hereditary cancer predisposition syndrome: a case report and review of literature. Biomark Res 3, 14 (2015). https://doi.org/10.1186/s40364-015-0040-5
BAP1 hereditary cancer predisposition syndrome


Hello, and welcome to the Forum Games Section!
- The objective of this game is quite simple, and that is to discover the answer to the definition that a player posts. The "definition" I refer to must be an exact quote of something EXAMINED in-game.
Each player receives ONE point for each correct answer.
Points are evaluated after every 100 posts.
2.) "What is..." must be the start of your sentence while answering a definition.
3.) Each definition has 3 days to be discovered. Anyone can post a new definition if undiscovered.
4.) Do not spam posts. Players can post again only after someone else has posted/replied.
If we undergo any issues or find any changes, speak up! I don't mind adding or removing a few things. Good luck, and I"ll help get us started!
"Has pillaged the dark crypts of Morytania."
"Plenty with which to feed many hungry stomachs." A wise man told me to come to the forums.
"A traveller's companion" Not so sure what I am doing on here yet but I will in no time!
"Built for smashing enemies and inspiring awe."


Baylor St. Luke's Emergency Center–Pearland brings quality emergency care from the Texas Medical Center to people of all ages in Pearland. Our community emergency center in Pearland is open 24 hours a day, 7 days a week to help you or a loved one get back to better health.
Baylor St. Luke's Emergency Centers are staffed by physicians, emergency-trained nurses and licensed radiology and laboratory technologists who offer Texas Medical Center quality emergency care closer to home.
Our Pearland community emergency center offers care for both children and adults with minor and major injuries or illnesses without the long wait at a hospital emergency department. As a hospital backed community emergency center, patients can expect to have access to on-call CHI St. Luke's Health specialists and seamless admission to a CHI St. Luke's Health Hospital when necessary.


Put Diesel in your petrol car? Put Petrol in your diesel car? Don't panic we can help, meet Fuel Doctor Paul, covering Lancashire & all the towns and can be with you within the hour!.
If you have put the wrong fuel in your car, be sure to call Paul, one of our qualified local engineers in Lancashire and the surrounding towns. We have Fuel Doctors covering all the local areas in and around Lancashire, however Paul is our main man for the county. Sometimes we may draft our Fuel Doctor from Manchester if Paul is busy. If you live in any of the following areas we can be with you within the hour and the process can take anything from 15 minutes to 30 mins to get you back on the road again. We cover the following towns in Lancashire, don't worry if you cannot see your town, we are nationwide so we have you covered.
Paul covers all the towns in Lancashire, he heads up the Lancashire depot, so if you have put the wrong fuel in your car call Paul and he will be with you within an hour and will perform a quick fuel drain & get you back on the road in no time.
Paul loves walking and rambling, spending time with his family, holidays in the sunshine and following his favourite team.
Everyday roughly 80 people will put the wrong fuel in their car in the Lancashire area, whether its diesel in petrol or petrol in diesel. It's a very common mistake and easily done, we understand that you need us there fast and to get back on your feet to get on with you life.
Mr Backshall put Petrol in his Diesel Audi A3 in Burnley Lancashire, he made it from the fuel station to the end of his home street and stalled the car. He gave our Lancashire Fuel Doctor a call, and we had the engine drained and cleaned and his vehicle was ready for use again when he headed to work the next morning.
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Miss Ryan put Diesel in her Petrol driven Volkswagen UP in Accrington Lancashire at her local Shell petrol station. She immediately realised her mistake and called us. Fuel Doctor Lancashire were on the scene within the hour and had her back on the road after the fuel drain.
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A HGV driver found himself stranded at Shell Fuel Station in Skelmersdale, Lancashire on Mothering Sunday 26/3/17.He made the simple mistake of filling his Honda CB1000 Superbike with Diesel instead of Petrol.
After driving heavy goods vehicles and a Diesel car his entire life, he admitted it was an easier mistake to make than he'd first thought.
Fuel Doctor attended this job on behalf of Greenflag breakdown. We arrived within 20 minutes and had the bike back on the road within a further 20 minutes.
This customer but petrol in his diesel Peugeot 207 at a filling station in Chorley. The car had been run and stalled in a car part around the corner.
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Lena on the Issues
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Editorials Columns
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Lena C. Taylor, Wisconsin State Senate, District 4
Reflect on the Past, Celebrate the Future
By Senator Lena C. Taylor
Black history month is a time for celebration and for reflection. We celebrate our rich history; all of the triumphs and all of the obstacles we've overcome. We reflect on the struggles of our past; the times of trial and the days where we could not see the light from the darkness of the perils that lay before us.
Frederick Douglass once said "If there is no struggle, there is no progress…This struggle may be a moral one; or it may be a physical one; or it may be both moral and physical; but it must be a struggle". I think about our ancestors fighting for the right to their freedom. I think of our ancestors fighting for the right to vote. I think of our ancestors fighting for the right to equality in the eyes of society. We truly stand on the shoulders of those who came before us and allow us to enjoy the benefits of all that they struggled for.
Because of those who suffered the horrors of slavery, we are now free from the shackles of the past. Because Ezekiel Gillespie refused to be denied the right to vote in Wisconsin, we can proudly go to the polls on Election Day and cast our ballot. And because of those who led the Civil Rights movement in the 1960's, we have a more equal society than 50 years ago. All of these efforts have moved us forward to where we are today, a place of hope and optimism.
Although February is designated as Black History Month (ironically the shortest month of the year), we don't need to limit our celebration to 28 days out of the year. If we're truly honoring all the achievements that African Americans have done for this country, it would surely take longer than one month. I get up everyday and celebrate Black History in my house.
Sen.Taylor@legis.wisconsin.gov
Madison Office - 608-266-5810
Room 5, South Wing
State Capitol , P.O. Box 7882
https://www.facebook.com/SenLenaTaylor


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Wholesale Kratom
What are the State Laws Regarding Kratom?
By david.the.beast January 21, 2021 January 16, 2022 Uncategorized
kratom, federal and state laws level
Despite its popularity in the United States, kratom remains something of a controversial product, largely due to the potentially heavy effects it can provide to the body. Therefore, it's natural that many people are hesitant to try it because they're not quite sure whether or not it's legal where they live.
Still, it's hard to deny that kratom is rapidly growing in popularity throughout America, and that more people are turning to it to manage their unique situations on a daily basis.
Kratom has been around for thousands of years. In fact, it has been used medicinally in the regions of Southeast Asia to which it is native. It's only really traveled to our part of the world recently, but already, it's proven to be a hugely successful market thanks to the fascinating properties within its alkaloids, which promise to help with everything from stress to pain.
Kratom is the dried leaves of the Mitragyna speciosa plant that grows abundantly in Thailand, Malaysia and other Southeast Asian countries. The leaves possess a unique variety of alkaloids that may offer strong effects to the human system, both physically and mentally. It comes in various forms, including the straight powder, along with capsules, tinctures, beverages and more.
Is Kratom Federally Legal?
Kratom remains an unregulated industry within the United States, which means that there is currently no governing body tasked with ensuring that it is produced to certain standards. Further, kratom has not been outlawed by the federal government, although there has been more and more push from legislators to move it to the list of classified substances in recent years. However, as of now, kratom is officially legal under federal law.
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On January 28, 2019, TCF fellow Yan Cao appeared before the New York Senate Finance Committee, the New York Assembly Ways and Means Committee, and the Senate and Assembly Higher Education Committees to testify at the Joint Legislative Budget Hearing on Higher Education about the importance of enacting a budget proposal, the For-Profit College Accountability Act, that would protect students from the growth of predatory practices in for-profit higher education.
The Century Foundation has previously called attention to the troubling outcomes of students who attend for-profit colleges in New York and has analyzed the policies within the For-Profit College Accountability Act, which was introduced in Governor Cuomo's 2020 executive budget.
The task today is to provide funding for higher education in New York. It is a critical task. At a time of rising inequality, economic insecurity for families, and fracturing among civil institutions, prying open the doors to offer high-quality affordable education to all New Yorkers remains the last best chance to improve the lives of individual students, uplift their families and communities, and drive economic growth.
Prying open the doors to offer high-quality affordable education to all New Yorkers remains the last best chance to improve the lives of individual students, uplift their families and communities, and drive economic growth.
But, with each effort to expand access to higher education, there has been an unfortunate record of abuse. From the very first GI Bill to the early days of Higher Education Act, and from state programs seeking to promote higher education for police officers to federal programs seeking to promote education for low-income mothers, well-intended programs meant to augment student financial aid for higher education have led to abuse.
Zach's experience is representative of the last major wave of growth in the for-profit college industry—in the wake of the recession, for-profit colleges grew as the rest of the economy contracted. New York's legislature responded in 2012 by enacting a law to protect students from some of the worst abuses. At the same time, the federal government woke up and improved accountability and oversight. These actions remain commendable and New York's leadership in that moment was clear.
But the work is not over. We face the potential for another cycle of abuse. Today, Secretary Betsy DeVos and others in the Trump administration actively seek to dismantle nearly every student protection that has been put in place.
The Gainful Employment Rule required vocational programs that consistently left graduates with high debt and low earning potential to improve student outcomes or risk losing federal aid eligibility. DeVos proposed eliminating this rule, allowing federal tax dollars to fuel rapid growth by for-profit programs, with no accountability required.
The Borrower Defense Rule offers cancellation of federal student loan debts for thousands of New Yorkers who were deceived and defrauded by for-profit colleges. DeVos has stopped investigating fraud and delayed help for defrauded students. Meanwhile, under her proposed revisions to the Borrower Defense Rule, defrauded students must default on their student loans before they can even apply for relief.
Federal rules on accreditation and state authorization are meant to promote quality and prevent from abuse. DeVos has reinstated an accreditor notorious for enabling rip-off chains like ITT Tech. Meanwhile, in a new round of changes started this month, DeVos has proposed standards that are so low, even the representatives of for-profit colleges are asking her to reconsider.
With these changes, federal student aid dollars that are meant to increase opportunity for students like Zach will instead fuel the growth of predatory colleges that prioritize profits over student success. History will repeat itself, and another generation of students will see their futures stymied by lifelong debt sentences unless states like New York break the cycle.
The good news is that we have the tools in place to safeguard students and improve outcomes. We know where the abuses are concentrated; we know the incentives that drive them; we know the common-sense accountability measures that stop them.
We know where the abuses are concentrated; we know the incentives that drive them; we know the common-sense accountability measures that stop them.
Where Is the Abuse Concentrated?
In New York, for-profit colleges enroll 4 percent of students but account for over 41 percent of student loan defaults.3 Moreover, they account for over 98 percent of student complaints of unlawful and deceptive activity by colleges and post-secondary institutions.4 Unlike other sectors, for-profit colleges have a mission to generate profit for owners and shareholders. This difference in mission is reflected in vastly different outcomes, as illustrated in the figure below.
Source: TCF analysis of data published by Ben Miller, Center for American Progress, Aug. 2018, available at https://www.americanprogress.org/issues/education-postsecondary/news/2018/08/30/457296/can-see-colleges-long-term-default-rate/.
Why Is Tuition High Instructional Spending Low at For-Profit Colleges?
For-profit colleges enroll vulnerable students, charge these students tuition at rates that are higher than those of public or non-profit colleges, but spend far less on student instruction.5 Directing vulnerable students to schools that provide the cheapest product at the highest price leads to predictably bad outcomes for these students, and does not serve the purposes of higher education funding on the whole.
However, this formula does respond to another mission of for-profit colleges: generating profit for the owners and investors who control decisions regarding tuition and instruction. For-profit colleges absorb the majority (57 percent) of federal grant aid as private profit.6 A 2012 U.S. Senate investigation found that for-profit colleges allocate 23 percent of revenue dollars to marketing and recruitment and 19 percent of revenue to profit while spending just 17 percent of revenue on instruction.7 These spending priorities are in line with the goals of owners and investors, but not with the goals of higher education funding in New York.
Comparing Annual Tuition Charges to Instructional Spending at Bachelor's Degree Programs in New York.
Are For-Profit Colleges Charging Inflated Prices?
Today's hearing is focused on funding higher education because the conventional wisdom holds that better funding improves students' outcomes. But the experience at for-profit colleges is that a large share of student aid is absorbed as private profit, increased tuition aid can make colleges less affordable, and greater spending does not translate to better education or outcomes for students.
Taking this into account, New York must pair the funding policy that the legislature will establish in the coming months with an accountability policy to ensure that private, for-profit colleges—particularly those that rely on state and federal aid for their revenue—provide higher-quality, and more-affordable, education to students.
Passage of the "For-Profit College Accountability Act," Part E of the Education, Labor and Family Assistance (ELFA) Bill, is a key step that will allow New York to offer a high-quality alternative to the predatory growth that federal education policy will unleash.
Archives of the Century, The Century Foundation, available at https://archivesofthecentury.org/.
Hastie's testimony is available here.
Joint hearing of the New York State Assembly Standing Committee on Banks, Standing Committee on Consumer Affairs, and Protection Examining Practices of the Student Loan Industry, November 27, 2018; written testimony of Kirsten Keefe, on behalf of the Empire Justice Center, and Yan Cao, on behalf of The Century Foundation, available at https://empirejustice.org/wp-content/uploads/2018/11/P_TEST-Student_Debt_November_2018.pdf.
Yan Cao and Tariq Habash, "College Complaints Unmasked," The Century Foundation, November 8, 2017, available at https://tcf.org/content/report/college-complaints-unmasked/ (finding 99 percent of student fraud claims concern for-profit colleges); Yan Cao and Tariq Habash, "College Fraud Claims Up 29 Percent Since August 2017," The Century Foundation, May 30, 2018, available at https://tcf.org/content/commentary/college-fraud-claims-29-percent-since-august-2017/.
ee Louise Seamster and Raphaël Charron-Chénier, "Predatory Inclusion and Education Debt: Rethinking the Racial Wealth Gap," Sage Publications, January 3, 2017 available at https://journals.sagepub.com/doi/abs/10.1177/2329496516686620?journalCode=scua ("actors offer needed services to black households but on exploitative terms that limit or eliminate their long-term benefits").
Christopher V. Lau, "The Incidence of Federal Subsidies in For-Profit Higher Education," Northwestern University, 2014 working paper, available at https://drive.google.com/file/d/0BxCDXfeTJUvWSU9pemdXdlZrOTg/view (finding that at for-profit colleges, 57 percent of federal grant aid and 50 percent of federal loan aid is absorbed as profit).
"For Profit Higher Education: The Failure to Safeguard the Federal Investment and Ensure Student Success," United States Senate Health, Education, Labor and Pensions (HELP) Committee, July 30, 2012, available at https://www.govinfo.gov/content/pkg/CPRT-112SPRT74931/pdf/CPRT-112SPRT74931.pdf.
David O. Lucca, Taylor Nadauld, Karen Shen, "Credit Supply and the Rise in College Tuition: Evidence from the Expansion in Federal Student Aid Programs," Federal Reserve Bank of New York, February, 2017, https://www.newyorkfed.org/medialibrary/media/research/staff_reports/sr733.pdf.
Stephanie Riegg Cellini and Claudia Goldin, "Does Federal Student Aid Raise Tuition? New Evidence on For-Profit Colleges," American Economic Journal: Economic Policy, volume 6, number 4, November, 2014, 174–206, http://dx.doi.org/10.1257/pol.6.4.174.
David O. Lucca, Taylor Nadauld, and Karen Shen, "Credit Supply and the Rise in College Tuition: Evidence from the Expansion in Federal Student Aid Programs," Federal Reserve Bank of New York, staff report 733, July, 2015, revised February, 2017, available at https://www.newyorkfed.org/medialibrary/media/research/staff_reports/sr733.pdf ("The rationale for the price increase . . . had to do with Title IV loan limit increases" (quoting Apollo Education Group, 2007:Q2 Earnings Call)).


text:
Summary: Man's Search for Meaning by Viktor E. Frankl
Meaningful Publishing Deanslibrary.com
NarratorDean Bokhari
Non-fictionPsychologyPolitics & WarHistoryYoung AdultNon Fiction for young adults
Man's Search For Meaning by Viktor E. Frankl : Audiobook Summary by Meaningful Publishing
About: Summary of Man's Search For Meaning by Viktor E. Frankl
Imagine what it would feel like to be seized like an animal and thrown into a Nazi concentration camp. What would be going through your mind? Would you lose all hope? Or manage to find hope and meaning in the middle of all that death and chaos? That's what Viktor Frankl did... Even after watching his entire family get murdered, he still found a way to see the light at the end of the tunnel for long enough to survive the brutality of the Nazi concentration camps in order to share his meaningful story with the world.
Published2019-12-12
PublisherAuthor's Republic
© Author's Republic (Audiobook)


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The Walnut Creek Police Department is the primary answering point for all 9-1-1 and non-emergency calls for the City of Walnut Creek. The communications center operates 24-hours a day, 7 days a week by a team of highly skilled and dedicated Public Safety Dispatchers. Our dispatchers serve as the vital link between those in need of help and emergency services personnel.
In 2017, our dispatchers processed close 85,000 incoming calls, over 23,000 of which were 9-1-1 calls. Our team proudly answered 98.89% of the 9-1-1 calls in less than 10 seconds. Dispatch created over 51,000 calls for service and made over 25,000 outgoing service calls for patrol.
You may dial 925-935-6400 for urgent situations that are not life-threatening emergencies.
Many non-emergent crimes or crime tips can be reported using our Online Crime Reporting system; click the link to see if your incident meets the criteria.
Refer to the Dispatch FAQ page for more information.
~Next to the thin blue line is the thin gold line which represents those who are rarely seen, but mostly heard.


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Ossining Girls Win Regional Finals vs. Binghamton
by Andrew Meola
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PLEASANTVILLE, N.Y. – Ossining is headed to the state semifinals.
The Pride will be one of the final four teams playing for the girl's New York State Class AA Championship. Ossining earned revenge over Binghamton to win the regional championship, 90-76. The Patriots defeated the Pride in the same round last year.
Saniya Chong had another predictably magnificent performance as she tallied 39 points, eight assists and four rebounds
"It's an awesome feeling," Chong said. "We came back in here for revenge because, obviously, we lost last year, so we were really striving for it and hoping."
Chong impressed nearly everyone in attendance, and hopefully left a mark on University of Connecticut women's basketball coach Geno Auriemma, who was in attendance to scout the guard.
"That's awesome. It just shows you how far our program's come and how far Saniya's come," said Ossining Head Coach Dan Ricci. "UConn only recruits quality people. Saniya's a quality kid.
Even with arguably the best college women's basketball coach in the country in attendance, Chong insisted she did not get rattled.
"It's not a big thing about pressure," Chong said. "I get little jitters when I'm outside, but once I step on the court, I'm fine.
The Ossining fans in attendance chanted "Goodbye Geno!" as the coach left the Goldstein Fitness Center.
Ossining actually struggled out of the gate and was behind, 7-4, to start the game and 13-12 at the 3:29 mark of the first quarter. The Pride held a small lead, 31-25, at the end of the first quarter.
But in the second quarter, the Pride blew the game open. A layup from Chong gave Ossining a 41-29 lead with 5:08 remaining in the second quarter. She drained a three from the top of the arc with a little more than a minute to go to extend the lead to 20 points.
Ossining led, 53-36, at the half and 68-52 at the end of the third quarter. Binghamton was never able to cut the lead to single digits.
The second quarter was the turning point, and Ricci said Chong was not the only catalyst for the Pride's surge.
"Everybody's going to say it's Saniya, but it was other kids making shots. Kathryn Polletta, Destini Walker, Jalay Knowles," Ricci said. "A lot of kids stepped up today."
Ossining, though undefeated, now faces a tall order in the state semifinals in Cicero-North Syracuse's 6'4" forward Breanna Stewart, whom Ricci called "probably the best player in the country."
Knowles, who had a great game of her own Friday, will have to guard Stewart, and Ricci did not sugarcoat what a tough task that will be.
"She's going to have to play huge against Breanna, but it's going to be a team effort," Ricci said. "Nobody's going to stop Breanna Stewart, just like nobody could stop Saniya Chong. It's going to be Ossining against Cicero-North (Syracuse), not those two (players)."


Applications for the ART Program are currently closed. Stay-tuned! We hope to launch a pilot program in 2015-2016. Please carefully review the applicant eligibility and program requirements before applying. The application deadline is TBA.
Open to current adjunct faculty who teach for MCC in the semester they participate in the program.
Regular employees of the college who also teach as adjuncts may apply, but must receive support from their immediate supervisor and cannot receive a stipend for their participation.
Applicants may only participate in the program once.
Must be able to attend all sessions, including the celebration, to be accepted to the program.
Attend all mandatory face-to-face sessions (16 hours). Sessions may not be made-up nor supplemented online. Participants who miss a session will be withdrawn from the program. Note: Participants who are more than 10 minutes late will be considered as absent and will be withdrawn from the program.
Submit all program assignments and activities in the ART course (approx. 24 hours of work) within the required time frame as outlined in the schedule.
Offer feedback on the Program as per the due dates within ART course.
Attend the Program Celebration event (2 hours).
Must get chair support for application to program. This support must be received from the chair in email to the ART Program Coordinator, Dr. Jennifer Strickland.
Carefully review all the dates prior to applying for the program. Participants must attend all sessions to complete the program. Sessions may not be made-up nor supplemented online. Participants who miss a session will be withdrawn from the program.
All online course components must be completed by the stated deadlines with the final project being submitted no later than TBA.
Note: Working dinners will be served at the four regular sessions and light refreshments will be offered at the celebration.
Check back! Applications are currently closed.


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Q: Graphics are slower in 11.10 after upgrade I just upgraded from 11.04 to 11.10 and i noticed that graphics are slower. I had the nvidia driver downloaded from their website in 11.04. After the upgrade the pc wouldn't actually boot in kernel 3.0, so i went to 2.x.38 and installed the nvidia driver from the repos. After this change, 3.0 was working but, as i said, with some regressions.OpenArena, for example, was slower.  Plus, I noticed in Openarena tearing and in FF too. It may be a system wide thing though, i don't know.
So my question is ... how can i verify if the driver is installed correct?
But if i understood the problem incorrect, please help me out identifying it!

A: this happened to me also, in 11.04 my graphics were fine but as soon as i fresh installed 11.10 it was slow, i have a system76 weldebeest with a gt430 card and on 11.04 nothing could stop it but in 11.10 i can barely do anything without lag its horrible and makes me sad...  i have drivers installed from the drivers applet, and i found a ppa that if you use to upgrade it helps the performance a tiny bit but this thing is still laggy as hell.
this is the ppa i used
http://blog.al4.co.nz/2011/10/slow-desktop-performance-on-ubuntu-11-10-with-nvidia-graphics-cards/
like i said this helps a little but performance sucks horribly in 11.10


Don Lafferty is the Chief Marketing Officer of Mingl Marketing Group, a Bucks County-based digital, inbound marketing agency, providing B2B and B2C clients with a full suite of services from strategic consulting to website design, graphic design, video production, copywriting, blogging, social media management and full analytical analysis.
Don helps companies integrate tools like social media and email marketing into their traditional marketing, publicity, and business development strategies. Since 2006, Don has been speaking about and teaching the effective uses of social media for B2B and B2C applications at conferences and universities nationwide.


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Now Reading : Shining A Light In Dark Corners
Shining A Light In Dark Corners
December 1, 2017 • Jeffrey Goldberg & Martin Baron
In September, the Institute and its partner, The Atlantic, held the annual Washington Ideas Forum in the heart of the nation's capital. The event gathered the nation's leaders in politics, business, health, science, technology, arts, culture, and journalism for three days of can't-miss conversation. In the center of US political power, leaders like Treasury Secretary Steven Mnuchin, Senator Chris Coons, Senator Jeff Flake, VotoLatino's Maria Teresa Kumar, Chef Tim Ma, WeWork's Adam Neumann, author Tim O'Brien, General (ret.) David Petraeus, the National Portrtait Gallery's Kim Sajet, artist Sheldon Scott, and the Broad Institute's Feng Zhang all tackled the most consequential issues facing the country and the world. Below, Jeffrey Goldberg, the editor-in-chief of The Atlantic, sat down with Martin Baron, the executive editor of The Washington Post, at Sidney Harman Hall to discuss journalism in the age of Trump. www.washingtonideas.com
Jeffrey Goldberg: I want to start maybe in an obvious place: truth and lies. What does it mean when a president of United States labels the media "the enemy of the people"?
Martin Baron: There could be long-term consequences that have a corrosive effect on the institution of the media and the press in this country. I'm very concerned about that. Donald Trump initially condemned us, and then tried to delegitimize us, and then even dehumanized us, saying that we were the lowest form of humanity. And then when that wasn't enough, he said we were the lowest form of life itself. It's very corrosive. The press is a fundamental institution in this country. We're provided for in the First Amendment of the Constitution. There's a reason that the Founders did that. The purpose is to hold government accountable.
JG: Is this period of hostility between the executive and the press truly unprecedented? You're the editor of the newspaper that broke and reported on Watergate. Can you put this in historical context?
MB: Watergate is probably the best analog to what's happening today. Richard Nixon was very hostile toward the press, so we were under constant attack. The press's standing with the American public was very low at that time. People perceived the investigation of the president, and the whole Watergate investigation, as being highly politically motivated. And then, ultimately, Nixon had to resign, and the standing of the press actually went up after that. Our approval ratings reached probably the highest point in memory. They were probably as high as they're ever going to get. They were in the mid-50s. We're always going to have people upset with us.
JG: There's a disagreement among several editors about the use of the word "lie" to describe things that the president has said.
MB: We have not rushed to use the word "lie" in headlines or in stories, because I think you have to actually have documented proof that whoever you're saying lied actually knew that what he or she was saying was in fact false. So we haven't used that. We've used "falsehood." We've said "untrue." Now, there may come a point where we would use that word, "lie," because it becomes evident that the president does know that what he's saying is not true. I think we're getting to that point.
JG: You recently put on the banner of The Washington Post, "Democracy Dies in Darkness," as the motto of the paper. Does that term risk making you part of the resistance?
MB: No. And we don't view ourselves as part of the resistance. The day after the inauguration, the president went to CIA headquarters and he said that he was at war with the media. Well, we're not at war. We're at work. We're doing the job that's provided for in the First Amendment of the Constitution. That phrase, "Democracy Dies in Darkness," is something that our owner, Jeff Bezos, wanted to do well before Trump was elected president. He wanted to capture our mission and synthesize it in a few words. And our mission is to shine light in dark corners, to hold government accountable.
We're not at war. We're at work. We're doing the job that's provided for in the First Amendment of the Constitution.
JG: Let me ask you about the upside of the Trump era vis-à-vis the press. Your newspaper just crossed a line: a million digital subscribers. The press seems to be benefiting from this fight, which the president initiated but which also seems to be helping our business.
MB: There's no question that we have experienced the "Trump bump." People want to support us because they want their government to be held accountable, particularly this administration. But there's more to it than that. Over the course of this election, and certainly this presidency, people have stopped taking the press for granted in a way that they did before. People took the press for granted in this country for decades, and now they've come to realize that we're actually fundamental to a democracy, to the health of a democracy, and that if they want quality journalism, they're going to have to support quality journalism by paying for it.
JG: How do you convince people who believe that you're presenting fake facts that, No, we have subjected our stories to a process of proving that this is empirically true. How do you convince people—and this goes to a larger question about the divisions in America—that, however imperfectly, we're actually trying to get at an observable fact?
MB: When we have stories that confirm people's preexisting points of view, they like those stories. They share those stories. Even the president has shared our stories on Twitter when he happens to like the story, and then in the next tweet he says we're fake news. So there's an internal inconsistency there.
Look, quality is really important. I participate in every hiring decision, because I think every person we hire can make a huge difference for the better—or for the worse. One reporter can make a huge difference in our success, but they could also cause us a huge problem. One copy editor can catch a serious mistake and prevent a disaster for us. So we try to be rigorous in the hiring process to make the right decisions. It's also important that we hire good editors to make sure they act as a quality-control mechanism in our news organization and that we emphasize editing as much as we do reporting as we continue to grow.


Welcome to the home of Galmington Dragons FC.
Galmington Dragons FC achieved The FA Charter Standard Development Club Accreditation in February 2010 and won the Somerset FA Chartered Standard Development Club of the Year award for Season 2010/2011.
The FA formally recognises this club as one that is not only committed to raising standards throughout grassroots football but also a club that has aspirations to further develop itself over the next three to five years.
The FA is very proud of its FA Charter Standard Development Clubs and understand and appreciates the work and commitment required to achieve this level of accreditation.
And finally, through all our best endeavors, to make the ball, without which there would be no game, HAPPY!