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Home / International / Dua Mangi's abductors demand $250,000 for her release
Dua Mangi's abductors demand $250,000 for her release
ISLAMABAD: Six days after Dua Mangi, a law student from Pakistan's Karachi, was abducted from an upscale neighbourhood of the crime-ridden city, her abductors have demanded a hefty ransom of $250,000 from her family for her release.
Dua, who is in her early twenties, was walking with her friend Haris Soomro on October 30 when unidentified attackers shot Soomro and took her away.
Police said the ransom demand was made through WhatsApp. Since the last three days, her family has been contacted several times, police sources said, adding that the abductors insisted on a ransom of $250,000 when they last contacted Dua's parents.
While many such cases, like the abduction of Hindu girls in rural parts of Sind province, that frequently take place across the country go unnoticed, Dua's abduction had raised a storm on social media after her sister, Laila Mangi, posted Dua's picture on Facebook with the news that she had been abducted. She asked her followers to keep an eye out and inform the family if they saw her anywhere. One of her cousins made a similar request on Twitter.
The responses on social media posts, however, turned into a verbal war between radical and moderate elements. Her critics blamed her for wearing a sleeveless top and roaming late at night with a male friend, pointing out that she deserved to be abducted as she asked for it. Dua's supporters, meanwhile, questioned the moral standards of her detractors.
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This is the first full-length biography of John Julius Angerstein, who was a considerable figure in the City of London and far beyond during the period 1770-1820. Born in St. Petersburg, he later moved to London. His exceptional abilities in marine insurance led him to later play a pivotal part in the development of Lloyd's. With increasing wealth and influence, he supported and founded charities, collected art, and was later a shipowner who raised the long-term finance which helped the British Government fund the Napoleonic Wars. With no successors to carry on his business, his achievements and his friendships with well known figures have been mostly forgotten. It is hoped that this book will reawaken the lost interest in this remarkable figures of late-Georgian England.


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Worcestershire Safeguarding Adults Board – advice and information on self-isolating
Saturday, 28th March 2020 /in Homepage, News /by Carole Hirst
Groups within the parish are being encouraged to register your efforts on the Worcestershire 'Here to Help' website at: http://www.worcestershire.gov.uk/here2help to help us see what is going on in local parishes during this pandemic.
There are two parts of the website one to register if you are offering help and one if you are asking for it.
Having organisations register on this site will help match individual needs to local help but also importantly give vital intelligence regarding any unmet individual needs and potentially support organisations to develop their local 'offer' to meet the needs of our communities.
WSAB Safeguarding adults info for self-isolating
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COVID 19: Police and Crime Commissioner- Working together to beat the virus
Thursday, 26th March 2020 /in Homepage, News /by Carole Hirst
COVID-19: Working together to beat the virus
The Coronavirus is a concern for us all across West Mercia and during these uncertain times we must work together to ease the situation. We all have our part to play and there are many ways to offer support to our communities' most vulnerable whilst ensuring personal safety. I have seen communities come together throughout Worcestershire to provide services such as collecting prescriptions, shopping or even offering phone calls to ensure those most vulnerable are still cared for and not lonely. As Commissioner I would encourage you all to keep safe and listen to guidelines issued by the Government and local authorities but keep community spirit going and look out for each other.
More information about offering support across Worcestershire can be found here: http://www.worcestershire.gov.uk/here2help
Police and Crime Commissioner John Campion
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Malvern Hills District Council advice on Social Distancing.
Click below to download Social Distancing Poster.
Social Distancing Poster
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Newsletter from MHDC "How we are responding to the Coronavirus Outbreak"
Tuesday, 24th March 2020 /in Homepage, News /by Carole Hirst
CLICK BELOW TO DOWNLOAD NEWSLETTER.
How we are responding to the coronavirus outbreak MHDC
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Parking issues at Abberley- Advice from Safer Neighbourhoods Team
Sunday, 22nd March 2020 /in Homepage, News /by Carole Hirst
The Parish Council have recently had reports of parking issues on The Common , Abberley.
Pedestrians having to squeeze past or walk in the road, Cars turning in from A443 often find themselves head on with vehicles leaving the Common.
We have contacted PCSO 6336 Vanessa Snape, our Community Support Officer of Martley and Tenbury Safer Neighbourhood Team and we detail her response below.
"IF a vehicle is causing an obstruction, call 101 with all the relevant information, an information log will be created. If it's 'antisocial' parking, then send an email to the team
with a photo; we can send a generic letter to the registered keeper of the vehicle."
Vanessa Snape
Police Community Support Officer 6336
Martley and Tenbury Safer Neighbourhood Team
E mail :
Voicemail 01905 725780
CRIME STOPPERS 0800 555 111
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Stay at home: guidance for households with possible coronavirus (COVID-19) infection – GOV.UK
Saturday, 21st March 2020 /in Homepage, News /by Carole Hirst
https://www.gov.uk/government/publications/covid-19-stay-at-home-guidance/stay-at-home-guidance-for-households-with-possible-coronavirus-covid-19-infection
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COVID-19: Five steps to look after yourself and others
Wednesday, 18th March 2020 /in Homepage, News /by Carole Hirst
Please see below banner and poster for Five steps to look after yourself and others COVID 19
COVID-19: Five steps to look after yourself and others BANNER
COVID-19: Five steps to look after yourself and others POSTER
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Cancellation of Parish Council Meeting Wednesday 18th March 2020
Cancellation of Parish Council Meetings
Following advice from Worcestershire CALC, Abberley Parish Council meeting scheduled for Wednesday 18th March has been cancelled due to restrictions imposed by the Coronavirus.
The Government advises that everyone implement what is termed social distancing with those who are over 70 and those who would normally get the flu jab to be particularly stringent in observing this advice. Social distancing includes avoiding large gatherings, and gatherings in smaller public spaces such as pubs, cinemas, restaurants, theatres, bars, clubs, Village Halls and Council meeting rooms.
Until we are informed by the Government that it is safe to do so, the Parish Council will be managing their business without formal meetings. This is in line with guidance provided by Worcestershire CALC.
Parishioners should check the Parish Council website and contact the Parish Clerk with any matter over which they have a concern or make written representation.
We apologise for this inconvenience at this time.
Carole Hirst
Clerk and Responsible Finance Officer.
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Coronavirus- Sources of Advice
Monday, 16th March 2020 /in Homepage, News /by Carole Hirst
The coronavirus situation is fast-moving and there is an increasing amount of misinformation online. We should be using government advice to inform decisions and be checking that advice regularly.
• Public Health England has FAQs that will be updated regularly
• This guidance, developed with the Department for Business, Energy and Industrial Strategy, aims to assist employers and businesses in providing advice to their staff
• You may find the advice from ACAS useful in considering any employment-related matters that may impact your local council
• For further reading, the Local Government Association has published a very useful list of different government advice sources
Regularly updated information for the public on the outbreak, including the current situation in the UK and advice about the virus and its symptoms, as well as statements from the Chief Medical Officer on confirmed cases in the UK.
The Government has published its Coronavirus action plan, which outlines what the health and social care system across the UK has done to tackle the outbreak, and what it plans to do next.
Public Health England has produced a dashboard with information on confirmed cases of coronavirus.
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Grant Funding for youth groups from the UK Youth Fund
Tuesday, 4th February 2020 /in Homepage, News /by Carole Hirst
UK Youth Fund
CLICK HERE TO DOWNLOAD FLYER FOR UK Youth Fund
Grants are available for third sector and statutory organisations in England to deliver extra sessions in youth
clubs and settings for young people or to enhance and expand existing sessions.
UK Youth, a national charity working with a network of local youth clubs and organisations to support young people
across the UK, is administering this Fund with funding being provided by the Department for Digital, Culture, Media and
Sport (DCMS) and the Youth Accelerator Fund.
Objectives of Fund
The aim of the Fund is to provide increased capacity and support for grassroots youth organisations in England, allowing
them to reach more young people.
A total of around £1 million will be awarded in grants.
Grants of between £3,000 and £20,000 are available.
Please note the grant must be spent before 31 March 2020.
The following organisations can apply:
• Voluntary and community organisations.
• Registered charities.
• Constituted groups and clubs.
• Not-for-profit companies or Community Interest Companies.
• Statutory bodies (including town, parish or community councils).
Preference will be given to organisations with an annual turnover of under £1 million.
Organisations must be members of the UK Youth Movement to be eligible. They can sign up for membership free of
charge on the UK Youth website.
Applicants must be able to spend the grant by 31 March 2020.
The following are not eligible for funding:
Alcohol.
• Contingency costs, loans, endowments or interest.
• Political or religious activities.
• Profit making activities.
• Fundraising.
• VAT that can be reclaimed.
• Statutory activities.
• Capital works or refurbishment costs.
Eligible Expenditure
The funding is for the delivery of extra sessions or the expansion of existing sessions in youth clubs in England, with the
aim of reaching more young people.
The grant can be used to cover the following costs:
• Equipment.
• One-off events.
• Staff costs.
• Training costs.
• Transport.
• Utilities/core running costs.
• Volunteer expenses.
The grant must be spent before 31 March 2020.
Applications will be accepted from Thursday, 30 January 2020 until 5pm on Tuesday, 11 February 2020.
Applications should be made as soon as possible as the application window may close early depending on the
number of applications received.
Guidance notes and the online application form are available on the UK Youth website.
Successful applicants will receive the funding within two weeks of the closing date.
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redpajama_set_name: RedPajamaCommonCrawl


A super crystal-clear vodka produced on the basis of 4-times distilled quality rye spirits. Taste qualities confirmed by a number of favourable opinions and awards place it among the best vodkas in Poland. It is the only vodka having double system of safety-locks: a hologram on the label and a special bond with hologram on the cap.
Adler is a vodka of delicate anf harmonious taste produced from excel mountain water and pure alcohol. The label is embossed on the bottle and carries authentic value and guaranties the originality of the products.


Oscar-winning actress Diane Keaton has purchased an 1880s building turned residence in downtown Tucson, AZ, for $1.5 million.
"Tucson is underappreciated," Keaton told Jimmy Kimmel this week, during a stop on his talk show.
Keaton, a veteran house flipper, had been eyeing downtown Tucson for a while, according to the Arizona Daily Star. She was contacted last summer by the writer Kathe Lison and her husband, Chris Cokinos, who had spent four years turning a vacant adobe building in Tucson's Barrio Viejo into a stylish, four-bedroom home.
Keaton saw the desert property, fell in love, and made the purchase in April.
It wasn't easy for Lison to part with the home she had created from the empty space. But ultimately, Keaton was able to make a $1.5 million offer the sellers simply couldn't refuse.
The rustic home is full of Southwestern charm, throughout its four bedrooms, 3.5 bathrooms and 4,500 square feet. The remodel was careful to maintain as much as possible of the building's original character, while carving out cozy, modern spaces in the cavernous building.
The property's prodigious price tag is a boon to real estate in the area, and may signal the beginning of a resurgence in the Barrio. In keeping with her penchant for flipping, Keaton told Kimmel she plans to sell the home eventually.
And the added bonus of a celebrity pedigree could drive the price even higher when Keaton places it back on the market. Local real estate agents are watching carefully, and activists fear that price spikes could irrevocably change the area and drive out low-income families in favor of affluent outside investors, according to the Daily Star.
Everyone with a stake in downtown Tucson will be watching this little building in the Barrio for signs of what's to come. For now, it's in the hands of a Hollywood legend with vision and a head for real estate. We can't wait to see how the plot unfolds.


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Review ArticleMini-Reviews
Biomarkers in ACS and Heart Failure: Should Men and Women Be Interpreted Differently?
Shweta R. Motiwala, Amy Sarma, James L. Januzzi, Michelle L. O'Donoghue
DOI: 10.1373/clinchem.2013.202531 Published December 2013
Shweta R. Motiwala
Department of Medicine, Massachusetts General Hospital, Boston, MA;
Amy Sarma
Department of Medicine, Brigham and Women's Hospital, Boston, MA;
James L. Januzzi
Cardiovascular Division, Massachusetts General Hospital, Boston, MA;
For correspondence: jjanuzzi@partners.org modonoghue@partners.org
Michelle L. O'Donoghue
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA.
BACKGROUND: Sex-based differences exist in the circulating concentrations of certain novel and established biomarkers in patients with acute coronary syndromes (ACS) and heart failure (HF). However, to date, few studies have compared the diagnostic and prognostic utility of these markers in men vs women.
CONTENT: This mini-review contains a discussion of the published reports of studies that have explored whether differences in biomarker concentrations exist between men and women with ACS or HF. It also examines those studies that have compared the utility of biomarkers for diagnosis or risk stratification in women vs men. Because biomarkers are often used to make therapeutic and triage decisions in patient care, the potential clinical implications for any observed differences in biomarker reference limits for men and women is discussed.
SUMMARY: Although the concentration distributions may differ between men and women for certain biomarkers in clinical use, the clinical implications of these observations remain unclear. Because elements of the pathophysiology of ACS and HF may differ between the sexes, further research is needed to better evaluate the diagnostic and prognostic utility of biomarkers in men vs women.
Although age-adjusted mortality rates have progressively declined during the past few decades, cardiovascular (CV)5 disease remains the leading cause of death in both men and women in the Western world. As our armamentarium of therapeutic options in the management of acute coronary syndromes (ACS) and heart failure (HF) continues to grow, there is continued interest in developing strategies that may help to identify those individuals at increased risk of adverse outcomes and those who may derive greater net benefit from evidence-based therapies. To that end, several established and novel biomarkers have been shown to be useful for risk stratification in patients with ACS and HF. Further, a subset of these biomarkers may help to identify those patients who derive enhanced benefit from particular treatment strategies. Although emerging data suggest that the pathophysiology of ACS and HF may differ between the sexes, little is known regarding the relative diagnostic and prognostic utility of biomarkers in men vs women.
Cardiac Troponin T and I in ACS
Cardiac troponin T (cTnT) and cTnI remain the gold standard for the diagnosis of myocardial infarction (MI) (1). In particular, a rise and/or fall in cardiac troponin concentrations with at least 1 value above the 99th percentile is a key feature for the diagnosis of a new event under the Universal Definition (1). In addition to the diagnostic utility of cardiac troponin, several studies have demonstrated that higher concentrations of cardiac troponin are independently associated with an increased risk of CV events in patients with ACS (2). Moreover, cardiac troponin concentrations may be useful for helping to identify those patients who may derive enhanced benefit from particular therapies in ACS, including glycoprotein IIb/IIIa receptor blockers or routine cardiac catheterization (2). However, few studies have compared the relative diagnostic or prognostic utility of cardiac troponin in men vs women.
This question may be particularly relevant given that several studies have shown that cardiac troponin concentrations are significantly higher in men than women in healthy individuals (Fig. 1) (3) and in those patients with stable coronary artery disease (CAD) (4). To date, it remains incompletely understood why mean cardiac troponin concentrations are higher in men than in women because cardiac troponin is presumed to be restricted to the cardiomyocyte. In contrast, the mean values of circulating creatine kinase MB (CK-MB) concentrations are higher in men than women owing to the higher skeletal muscle mass in the average male study participant, because CK-MB comprises 1%–2% of the creatine kinase originating from skeletal muscle.
Fig. 1. The distribution of high-sensitivity (hs)-cTnT concentrations in a pooled reference population.
The 99th percentile for the pooled population was 13.5 ng/L. The inserts show the distribution of hs-cTnT among women versus men; the 99th percentile was significantly higher in men than women (14.5 ng/L versus 10.0 ng/L) [reproduced with permission from Giannitsis et al. (3)].
It is plausible that a higher mean cardiac mass may be responsible for the higher cardiac troponin concentrations in males because the weight-adjusted cardiac troponin content has been shown to be similar in male and female myocardial tissue (5). However, it remains unknown whether the release and clearance kinetics of cardiac troponin are similar in men and women in response to ischemic injury. Intriguing data from 1 small study demonstrated that the perioperative release of cardiac troponin was 3-fold greater in men than women in response to a similar ischemic insult during cardiac surgery, despite similar exposure to cardiopulmonary bypass and aortic cross-clamping times in age and risk-factor matched male and female study participants with a comparable body mass index (6). It is therefore plausible that sex-based differences may exist with respect to cardiac troponin release at the level of the cardiac myocyte; however, this requires further study. Another contributing factor to sex-based differences in cardiac troponin concentrations in stable or unstable CAD may be related to the fact that women are less likely than men to have obstructive macrovascular CAD at catheterization (7) and less extensive disease (8), and therefore differences in cardiac troponin release could reflect pathophysiological differences in CAD between the sexes, including a higher prevalence of microvascular disease, endothelial dysfunction, or more diffuse atherosclerosis in women. To that end, the higher prevalence of a patent epicardial vessel in women with ACS could potentially influence the washout kinetics of cardiac troponin from the interstitium and therefore blunt the peak concentration of cardiac troponin detected in the periphery (9).
Importantly, it remains unclear whether the observed differences in mean cardiac troponin concentrations in men vs women have clinical implications. Under the Universal Definition of MI, a rise and/or fall in cardiac troponin exceeding the 99th percentile in a normal reference population is required to be diagnostic of a new event (1). Since the MI reference limit is often employed to make key therapeutic and triage decisions in patient care, it is of upmost importance to correctly identify this threshold for a given patient population. However, the established approach toward determining manufacturer assay reference limits is to assess the distribution of cardiac troponin concentrations in a healthy population with a roughly even split between men and women. Therefore, in many instances the stated manufacturer reference limit exists beyond the "true" 99th percentile in a healthy female population (10–12) and for some assays can be as much as 5 times higher in healthy men vs women (12).
More recently, the advent of high-sensitivity cardiac troponin assays has allowed for the ascertainment of very low concentrations of circulating cardiac troponin with greater precision at concentrations that were previously undetectable with earlier generations of the assay. High-sensitivity assays have revealed that low concentrations of cardiac troponin are present in a large proportion of healthy-appearing individuals (13, 14), including 98% of patients with stable CAD (4). Men have been shown to have more extensive CAD than women, and the extent of coronary atherosclerosis has been shown to be associated with increasing circulating concentrations of high-sensitivity cardiac troponin (8). Given their higher precision at the lower range, it is plausible that the high-sensitivity assays will only further unmask sex differences that may not have been as apparent with less sensitive generations of assays. Consistent with analytical validations conducted with earlier assays, independent evaluations of high-sensitivity cardiac troponin assays have demonstrated that the 99th percentile appears to be consistently higher in men than women for several of the high-sensitivity cardiac troponin assays (3, 12, 15). Research is ongoing to help determine whether serial changes in cardiac troponin concentrations may therefore be a more reliable indicator of myocardial injury in women, compared to an approach that requires a single diagnostic cutpoint. This type of strategy would place greater emphasis on the relative changes in cardiac troponin concentrations in the setting of ischemic symptoms, rather than relying on an absolute threshold.
Beyond the diagnostic utility of cardiac troponin, the relative prognostic value of cardiac troponin in men vs women has not been rigorously evaluated to date. In a small substudy of individuals with unstable coronary disease who underwent a symptom-limited stress test, the prognostic value of cTnT with an older generation assay was comparable in both men and women (16). Similarly, in TACTICS-TIMI (Treat Angina With Aggrastat and Determine the Cost of Therapy With an Invasive or Conservative Strategy–Thrombolysis in Myocardial Infarction) 18, the prognostic value of cardiac troponin after NSTE-ACS was broadly equivalent in men and women, although the marker appeared to be a stronger predictor of recurrent MI in women than men (17), a finding supported by a second independent analysis (18). In contrast, the prognostic value of periprocedural myonecrosis in men vs women has yielded conflicting results (19, 20).
At this time, it is unknown whether the absence of sex-specific decision limits for the diagnosis of MI contributes to the underdiagnosis and undertreatment of ACS in women compared to men. Several studies have demonstrated that women represent a high-risk group who receive fewer guideline-recommended therapies in the setting of ACS, including less frequent cardiac catheterization and use of secondary prevention therapies. After the 2000 European Society of Cardiology and American College of Cardiology guidelines placed greater emphasis on the use of cardiac troponin for the diagnosis of ACS, a study in Israel suggested that implementation of the revised recommendations was associated with a reduction in the sex-based mortality difference in patients with ACS despite the fact that an early invasive strategy and secondary prevention continued to be underutilized in female patients. In part this difference appeared to be explained by increased use of guideline-based therapies in both men and women (21).
More recently, the 2007 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the management of unstable angina and non-ST-elevation MI (NSTE-MI) established sex-specific recommendations such that a conservative treatment strategy is recommended for low-risk women, including those women with negative cardiac biomarkers (2). These recommendations are supported by analyses from randomized trials that have demonstrated an apparent lack of benefit from a routine invasive strategy in women without increased cardiac biomarkers of myonecrosis (7, 17). Identification of an appropriate MI decision limit for cardiac troponin in women is therefore crucial because a decision limit that is too high could lead to misclassification of women as being lower risk and influence key management decisions.
Supporting this concern, an analysis from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) database demonstrated that patients with low concentrations of cardiac troponin or gray-zone increases that fell below the diagnostic cutpoint for MI were significantly less likely to receive guideline recommended acute and discharge therapies in the setting of ACS (22). This hypothesis is also supported in part by the fact that women are significantly less likely than men to have cardiac troponin concentrations that rise above the MI decision limit despite a presentation suggestive of ACS (7). In the TACTICS-TIMI 18 trial, women with NSTE-ACS were nearly half as likely as men to have increased cTnT [odds ratio (OR), 0.53; 95% CI, 0.43–0.68] or cTnI (OR, 0.58; 95% CI, 0.46–0.73) concentrations at study entry after taking into account baseline differences (Fig. 2) (17).
Fig. 2. In a large clinical trial population of patients with NSTE-ACS, men were significantly more likely than women to have a significant increase in CK-MB or cardiac troponin concentration at presentation.
After taking into account baseline differences, women were 47% less likely than men to have an increased cTnT (OR, 0.53; 95% CI, 0.43–0.68) and were 42% less likely to have an increased cTnI (OR, 0.58; 95% CI, 0.46–0.73) concentration at study entry [Wiviott et al. (17)]. CABG, coronary artery bypass graft; PTCA, percutaneous transluminal coronary angioplasty.
Based on the observed differences in cardiac troponin concentrations in men and women, some individuals have advocated for separate sex-specific 99th percentile reference limits for all cardiac troponin assays (12); however, to date such recommendations have not yet been adopted. In part, the reluctance to embrace sex-specific cutpoints stems from a lack of studies demonstrating that a small shift in a diagnostic or prognostic cutpoint will have clinical implications. Higher concentrations of high-sensitivity cardiac troponin were associated with future coronary events in both healthy men and women (23), as well as all-cause mortality in a study of healthy perimenopausal women (24). Whether the prognostic value of high-sensitivity cardiac troponin in healthy populations differs by sex, however, is unclear. Although the newest generation of cardiac troponin assays has allowed a lower diagnostic cutoff through implementation of more analytically sensitive and precise assays, the diagnostic specificity of the assay results for identifying individuals with myonecrosis due to coronary plaque rupture may be reduced. To that end, several studies have demonstrated that women are less likely than men to have evidence of obstructive macrovascular disease at the time of coronary angiography despite a presumed diagnosis of ACS (7). It has been hypothesized that this may be due to a higher prevalence of microvascular disease in women or disease states that mimic ACS, including myocarditis and HF. Therefore it will be important to determine whether low concentrations of cardiac troponin carry the same diagnostic and prognostic value in both sexes and whether these low concentrations should be used to guide clinical decision-making.
Other Biomarkers for Risk Stratification in ACS
Although there are few studies that have rigorously compared the diagnostic and prognostic utility of cardiac troponin in men vs women, this is especially true of other novel and established biomarkers in the setting of ACS. In TACTICS-TIMI 18, women with NSTE-ACS were significantly more likely than men to have an increased concentration of high-sensitivity C-reactive protein (CRP) or B-type natriuretic peptide (BNP), even after controlling for baseline differences. Despite these differences in baseline concentrations, the prognostic value of these markers for predicting CV events appeared to be broadly equivalent in both sexes (17). In addition, a multimarker approach that included cTnI or T, high-sensitivity CRP, or BNP was useful for helping to identify more women at increased odds of death or MI than any marker on its own and also helped to identify those individuals with a greater benefit from an invasive strategy. The prognostic value of the multimarker score for predicting the odds of death or MI was comparable between sexes (17).
Biomarkers in HF
In addition to their utility for patients with ACS, biomarkers have emerged as useful and powerful adjuncts to clinical judgment and guideline-directed medical therapy in the risk stratification and management of patients with HF. The most extensively studied markers have now been incorporated into current clinical practice guidelines (25), while new biomarkers continue to be identified and investigated for their abilities to reflect underlying pathophysiologic process involved in HF development and progression. If the clinical use of HF biomarkers eventually becomes more widespread, it will become increasingly important to understand analytical factors to correctly interpret and apply the results. Specifically, one aspect to consider is how sex-related differences in biomarker concentrations may affect their interpretation. For example, while the biological variability of the natriuretic peptides has been studied in detail in laboratory studies (26), much remains unknown about the interaction between such variation and clinical applications over extended periods of time; similar issues will emerge as other emerging biomarkers are being studied relative to their importance as serial monitoring tools (27). Additionally, not factored into this entire question is how sex affects biological variation. This is not an insignificant question, because several biomarkers most widely used for CV disease evaluation have sex-related differences in their reference intervals. These analytical issues reveal the complexity of sex-based application of biomarker testing.
NATRIURETIC PEPTIDES
BNP and amino-terminal pro BNP (NT-proBNP) are both released primarily in response to myocyte stretch and provide important information related to HF diagnosis, prognosis, and response to HF therapy. Several population-based studies have demonstrated that, in health, sex is one of the strongest predictors of circulating NP concentrations. These studies have shown that healthy women have higher concentrations than healthy men and have suggested that sex-specific reference limits could be helpful in guiding clinical use of NPs for diagnostic purposes (28, 29). However, cutpoints based on these reference intervals have not been conclusively established and have not yet been validated for use in the clinical setting.
The mechanisms that explain these differences are not entirely clear, but experimental and human studies have suggested that sex hormones may play a role. One murine-based study demonstrated that treatment with estradiol and progesterone stimulated NP gene expression in females (30), while another study demonstrated that testosterone suppressed volume-stimulated NP release from isolated perfused rat atria (31). Clinically, a study of postmenopausal women demonstrated a significant increase in mean BNP concentrations after transdermal estradiol administration (32), while observational studies have identified inverse correlations between circulating androgens and NP concentrations (Fig. 3) (33, 34). These findings have led to speculation that the generally higher NP concentrations in healthy women may be explained by a combination of estrogen-mediated stimulation and androgen-mediated suppression. Understanding these mechanisms and establishing sex-based reference intervals may improve the usefulness of NP measurement for screening purposes in low-risk, asymptomatic patients.
Fig. 3. Association between circulating free testosterone and NP concentrations.
(A), Data points represent median (25th and 75th percentiles) for each quartile (Q) of cFT (calculated free testosterone) concentration [adapted with permission from Chang et al. (33)]. (B), Least squares means and SE of log NT-proBNP are shown for each sex-specific quartile (I to IV) of FT (free testosterone) in men and women [reproduced with permission from Lam et al. (34)].
On the other hand, in disease states of acute and chronic HF, sex differences in NP concentrations are less obvious and are rather influenced by the sex-related differences in the epidemiology of HF. Studies have reported no statistically significant differences between BNP or NT-proBNP concentrations in female vs male patients with acute or chronic HF (35, 36), with women demonstrating slightly lower values. This paradox may be explained by the observation that women are more likely than men to have HF with preserved ejection fraction (37), which is a distinct pathophysiologic state associated with lower NP concentrations (38). Therefore, in HF, the sex-based difference in NP concentrations may be attenuated such that women with HF are more likely to have higher NP concentrations at baseline and smaller increases in the setting of preserved ejection fraction than men with HF, who may have lower concentrations at baseline but larger increases in the setting of systolic dysfunction. This difference in the prevalence of HF with preserved ejection fraction may be the major reason why studies have failed to show significant differences between NP concentrations in men and women with HF.
Importantly, despite these modifying factors, NPs retain their usefulness for the evaluation of female patients with acute dyspnea. In 1 large study, ROC curve analyses of BNP for diagnosis of acute HF as a function of sex demonstrated only slightly weaker diagnostic utility for females compared with males (areas under the curve, 0.870 and 0.918, respectively) (39), whereas another study of NT-proBNP demonstrated essentially no difference based on sex (35). Based on these findings, there is no clear evidence that sex-based criteria should be required when using NPs for diagnosis of acute HF in patients with dyspnea in the emergency department.
CARDIAC TROPONINS
As previously noted, cardiac troponin is the gold standard for the diagnosis of acute MI, but cardiac troponin is also often detectable in patients with HF regardless of whether underlying CAD is present (40). Furthermore, increased cardiac troponin concentrations are associated with worse clinical outcomes and increased mortality in both acute and chronic HF (40). With the advent of high-sensitivity cardiac troponin assays, cardiac troponin is now detectable in the vast majority of individuals independent of any known underlying disease state (13, 14), in whom its presence is associated with traditional CV risk factors and structural changes, as well as male sex. As noted previously, in presumably healthy populations, high-sensitivity cardiac troponin measured by multiple different assays has been shown to have significantly higher 99th percentile values for males than for females, which has led to the consideration of sex-specific 99th percentile reference intervals.
In the context of chronic HF, high-sensitivity cardiac troponin is measurable in almost all patients, and 1 study of patients with systolic HF showed that women were more likely than men to have concentrations above the sex-specific 99th percentile for the assay (41). It remains unclear whether this has clinical meaning, and further studies are needed to better understand this observation.
Novel and Emerging Biomarkers
In recent years, the field of biomarkers in the setting of HF has continued to expand and some are beginning to enter the realm of clinical practice. One of these is galectin-3, a marker that has been hypothesized to play a direct role in the progression of HF via mediation of myocardial fibrosis, although the data to date remain inconclusive. Higher concentrations of galectin-3 have been associated with increased risk for incident HF in the general population (42), as well as with an increased risk of adverse outcomes in patients with HF (43). In large population-based studies, concentrations of galectin-3 have been generally higher in women than in men, and have been associated with traditional CV risk factors, with stronger correlations observed in women (42). To date, sex-related differences in galectin-3 concentrations have not been well-established in HF.
Another new biomarker is soluble ST2 (sST2), which is strongly associated with myocardial fibrosis and hypertrophy through its interaction with interleukin-33. Higher concentrations of sST2 have been associated with greater CV risk of incident HF in the general population (44) and in patients with acute HF (45). In a large population-based study, higher circulating sST2 concentrations were associated with traditional CV risk factors and male sex (46). Concentrations were significantly lower in women than in age-matched men, and even lower in women taking estrogen replacement, suggesting that these differences may represent the effects of sex hormones (Fig. 4). In the context of acute or chronic HF, our experience has been that sex-related differences in sST2 concentrations are less apparent; much like the NPs, no adjustments in reference intervals appear to be necessary when using sST2 in symptomatic women with HF.
Fig. 4. sST2 concentrations in men and women in the reference sample [adapted with permission from Coglianese et al. (46)].
Another novel biomarker of interest is growth differentiation factor-15 (GDF-15), a stress-responsive cytokine that is a marker for inflammation and is synthesized by multiple organs including the placenta. Higher concentrations of GDF-15 have been associated with greater risk of incident HF in the general population (44) and are also associated with disease severity and prognosis in chronic HF (47). Concentrations may be lower in women with HF than in men (36), although the clinical implications of these observations are unknown.
An intriguing new biomarker that has been linked to risk for cardiometabolic disease specifically in women is proneurotensin (PNT). PNT is a stable precursor to neurotensin, a hormone that has been linked to satiety and obesity, and a receptor for PNT is a major human CAD susceptibility gene variant. A large population-based study demonstrated that PNT concentrations were significantly higher in women and predicted the onset of diabetes mellitus, CV disease including coronary events and stroke, breast cancer, and death; however, this relationship was observed only in women (48). Though the mechanisms for these relationships and their clinical implications are not entirely clear, these initial epidemiological results suggest that PNT may be useful for identifying women at high overall CV risk in the absence of traditional risk factors. The role of PNT to predict HF bears examination, and further studies are ongoing to evaluate this novel potential marker of women's health.
Sex-based variations may exist in the circulating concentrations of some established and novel biomarkers for diagnosis and risk assessment in patients with ACS or HF. However, it remains incompletely understood whether these observed differences are explained by dissimilarities in the prevalence of underlying comorbid conditions or whether they reflect fundamental discrepancies in the underlying pathobiology of ACS and HF in men vs women. To date, few studies have rigorously compared the diagnostic or prognostic utility of candidate biomarkers in both sexes. As such, it remains incompletely understood whether sex-specific reference limits should be adopted for biomarkers that are used in routine clinical practice. Although the clinical consequences remain unknown, such decisions would be anticipated to have the most relevance for those biomarkers that are used to help guide clinical decision-making. Research in this area is therefore needed to continue to optimize care and improve patient outcomes in at-risk patient groups. In addition, a better understanding of these differences may provide a unique window into the underlying biology of the disease process in both men and women.
↵† Shweta Motiwala and Amy Sarma contributed equally to the work, and both should be considered as first authors.
↵5 Nonstandard abbreviations:
cardiovascular;
ACS,
acute coronary syndromes;
HF,
heart failure;
cTnT,
cardiac troponin T;
myocardial infarction;
CK-MB,
creatine kinase;
TACTICS-TIMI,
Treat Angina With Aggrastat and Determine the Cost of Therapy With an Invasive or Conservative Strategy–Thrombolysis in Myocardial Infarction;
ACC,
American College of Cardiology;
American Heart Association;
NSTE-MI,
non-ST-elevation MI;
odds ratio;
CRP,
C-reactive protein;
BNP,
B-type natriuretic peptide;
NT-proBNP,
amino-terminal pro BNP;
sST2,
soluble ST2;
GDF-15,
growth differentiation factor-15;
PNT,
proneurotensin.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest:
Employment or Leadership: None declared.
Consultant or Advisory Role: J.L. Januzzi, Roche, Critical Diagnostics, Amgen, Novartis, and Zensun; M.L. O'Donoghue, Aegerion.
Stock Ownership: None declared.
Honoraria: None declared.
Research Funding: S. Motiwala, Dennis and Marilyn Barry Fellowship in Cardiology; J.L. Januzzi, the Roman W. DeSanctis Clinical Scholar Endowment, Roche, Critical Diagnostics, Siemens, BG Medicine, Thermo Fisher, Singulex, and BRAHMS; M.L. O'Donoghue, GlaxoSmithKline, AstraZeneca, and Genzyme.
Expert Testimony: None declared.
Patents: None declared.
Received for publication June 28, 2013.
Accepted for publication October 22, 2013.
© 2014 The American Association for Clinical Chemistry
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Charles Dickens Writes a Christmas Carol was written by a local community member, who has been involved with Lost and Found Theatre for several years. At first, it was performed as a live reading, but a few years ago it was decided to show it as a full production again.
"It's the biggest show we've ever done," continued Kathleen.
Lost and Found Theatre is unique in that it always strives to work with local writers, actors, and producers. For this particular production, Lost and Found recruited singers for the chorus, as well as actors for all of the main roles. Involving up-and-coming performers allows them to gain experience, and learn the ins and outs of how a theatre company operates.
The public is welcome to come out and watch one of the productions. They are family-friendly, and a sure way to get everyone excited for the holidays. Plus, a portion of all proceeds are donated to The Waterloo Region Record's Books for Kids program.
More information about Charles Dickens Writes a Christmas Carol, and other Lost and Found Theatre productions, can be found online at http://www.lostandfoundtheatre.ca.


text:
Take a steam train to Devon from Temple Meads this summer
Passengers can enjoy the sights from a traditional locomotive on board the Royal Duchy
Millie ReevesCommercial Writer
The Royal Duchy is a scenic ride through Devon and Cornwall
Passengers can step back in time to the Golden Age of railway travel with a day out on board a traditional steam train this summer.
The Railway Touring Company's excursions offer journeys on board some of Britain's finest surviving steam locomotives.
The company offers a range of trips including The Royal Duchy - a scenic ride through Devon and Cornwall, departing from Bristol Temple Meads.
These excursions will take place on four Saturdays from July to September, and could make a great family day out, a romantic trip for two, or a gift for a loved one.
For the train buffs out there, the train will be steam hauled by either No.60009 Union of South Africa or Black 5 locomotive No.45305.
Departing from Bristol, there will be stops to pick up further passengers at Yatton, Taunton and Exeter St David's.
Leaving Exeter, the steam adventure will follow the Exe Estuary and the famous sea wall between Dawlish and Teignmouth.
After Newton Abbot, the steam locomotive will power up and down some of the steepest main line gradients in the country.
The first stop will be Plymouth, where passengers can choose to alight if they wish and spend the afternoon exploring the maritime city, including the Hoe, ancient Barbican seafront and National Marine Aquarium.
Alternatively, the train will continue onto the Cornish countryside to the town of Par, where there will be a break for a few hours to explore the area.
There are a few dining options to choose from
There will be buses provided, included in the ticket price, to visit either the seaside town of Fowey or the harbour village of Charlestown.
The train will leave Par at around 5:45pm, picking up those passengers who chose to stay in Plymouth on the way, before returning to Bristol.
Whilst on board the train, there are a range of tickets with various carriage options and food services.
Standard Class includes a reserved seat, usually for a table of four and there is a buffet car available serving tea, coffee, snacks and light refreshments.
A First Class ticket includes a morning coffee with a muffin, and an afternoon service of tea or coffee with a cake and a biscuit.
Premier Dining includes a full English breakfast and a four course dinner served at your seat.
The Royal Duchy sets off from Bristol Temple Meads at 8:45am, returning around 10:45pm, with trips on July 21, August 4, September 1 and September 15.
For full information and tickets, visit: http://www.railwaytouring.net/uk-day-trips/the-royal-duchy
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It is with great pleasure to have attended the recent 2012 National Olive Conference & Trade Exhibition by the Australian Olive Association.
As the official sponsor of The Olive Centre's Grove of the Year Award bought prestige to the night being won by Victorian Olive Oil Project (better known as Redisland).
Also, Golden Creek Olives, Gold Award & Best of Class winner with their blend of Arbequina & Picual processed on their new Oliomio machine was described as 'Interesting flavours of green banana and honeydew melon. Some tropical and citrus flavours add to the palate. A slowly building bitterness and pepperiness. An elegant oil, with all points in balance".
A consistent performer Cradle Coast Olives, again won GOLD with their Essence of the Cradle Extra Virgin Olive Oil described as "Fresh complex green olive and almond aromas. Lively green banana flavours with a persistent spicy pungency. Strongly supported by Chair. Cradle Coast have won the Best Australian Extra Virgin Olive Oil in previous years and consistently achieve many of the top awards at a National Level.
Congratulations to our other winners Cape Schanck Olive Estate, Rash Valley Olives, Yalbury Olives, Lentara Olives, L'Oliveraie and Camilo Enterprises.
Confirming that with the combination of latest technology, The Olive Centre backup support in combination with working one-on-one with our growers can make a multi-award winning combination. The diversity of growing conditions and the matching of the right technology for each project proves that The Olive Centre can help you to achieve the maximum from your grove!


text:
Week In Politics: Robert Mueller Testifies Before Congress
By editor • Jul 26, 2019
This week's Mueller testimony brought the same words over and over again, like an echo - collusion, obstruction and, also, read the report. People received the special counsel's testimony very differently depending on who was listening.
In A Bitterly Divided Nation, Will Robert Mueller's Testimony Change Any Minds?
By Philip Ewing • Jul 25, 2019
Former special counsel Robert Mueller did what Democrats wanted him to do on Wednesday — the question now is how much difference that may make.
Mueller's hearings did not feature a telegenic star who could deliver a message as exuberantly as President Trump's opponents hoped.
Mueller On Russian Election Interference: 'They're Doing It As We Sit Here'
Peril from foreign interference in American elections will persist through the 2020 presidential race, former special counsel Robert Mueller warned on Wednesday.
Asked whether Russia would attempt to attack future U.S. elections, as it did in 2016, Mueller replied: "They're doing it as we sit here."
Mueller didn't detail a prescription for how he believes Congress or the United States should respond, but he recommended generally that intelligence and law enforcement agencies should work together.
6 Questions Congress May Ask Robert Mueller During His Testimony
Former special counsel Robert Mueller is testifying before Congress on Wednesday, and lawmakers have so many questions they may not have enough time to ask them all.
The House judiciary and intelligence committees have scheduled hearings for 8:30 a.m. and noon.
Majority Democrats and minority Republicans are expected to try their utmost to get the most good they can from Mueller — in very different ways.
Committee Democrats Prepare For Highly Anticipated Robert Mueller Hearings
By Tim Mak • Jul 19, 2019
Members of Congress likely won't confine themselves to former special counsel Robert Mueller's report when they question him next week in two open hearings, staffers said.
Mueller, who is reluctant to appear, has said he would confine himself to what he's already written — but the House Permanent Select Committee on Intelligence won't.
Robert Mueller To Testify In Open Hearings On July 17 Before House Committees
By Ryan Lucas • Jun 26, 2019
Robert Mueller has agreed to testify before the House Judiciary and Intelligence committees about his investigation into Russian interference in the 2016 election and possible obstruction of justice by President Trump, giving Democrats the star witness they have long wanted to put before the American public.
House Democrats To Get Some Mueller Report Material, But Contempt Vote Is Still On
By Philip Ewing • Jun 10, 2019
The Justice Department is to begin providing documents to the House Judiciary Committee after a dispute over a subpoena — but members of Congress are reserving the ability to continue to pursue contempt litigation down the line.
Top Democrat 'Confident' Mueller Will Testify 'Soon.' Here's What Congress Might Ask
By Philip Ewing • Jun 5, 2019
Former special counsel Robert Mueller says he would try to be an unappealing witness for Congress, promising he wouldn't say anything he hasn't said before.
House Democrats say that still sounds pretty good.
House Judiciary Committee Chairman Jerry Nadler, D-N.Y., reaffirmed on Wednesday that he continues to want Mueller to speak before his panel.
"Let's just say I'm confident he'll come in soon," Nadler told reporters.
He also emphasized that Mueller should testify in the open, not behind closed doors as the former special counsel had mused.
Democrats' Dilemma: Would Pushing For Mueller To Testify Hurt Or Help?
Democratic House members returning from recess this week must tackle another new dilemma over the results of the Russia investigation: what to do about Robert Mueller.
The outgoing Justice Department special counsel has said, in so many words, that he's said all he's got to say and that he does not want to appear in what would likely become a traffic-stopping set-piece hearing before a congressional committee.
Barr: Mueller Could Have Said Whether Trump Broke The Law, Just Not Charged Him
Former special counsel Robert Mueller could have declared whether President Trump broke the law if Mueller had wanted — albeit still without the ability to bring any indictment, Attorney General William Barr says in a new TV interview.
Barr told CBS News in an interview scheduled to air on Thursday evening and Friday morning that he believed Mueller had more latitude to state his views than the special counsel may have permitted himself.


By the time Sunday morning rolls around, we will know who is in the finals of the Bellator Heavyweight Grand Prix.
Honestly, for as weird and drawn out as the GP has been, it is kind of exciting to think about the semifinal matches that will air live on Paramount Network Friday and Saturday night.
First up will be Ryan Bader and Matt Mitrione at Bellator 207. Both are former contestants on The Ultimate Fighter and ex-UFC fighters, with Bader currently holding the light heavyweight title.
Mitrione, though, has been on fire since coming over to Bellator, including a finish vs. Fedor Emelinaneko.
Which leads us into Saturday's main event at Bellator 208 as Fedor battles the long-winded Chael Sonnen. It's been an impressive career for Sonnen, who has fought for UFC gold at both middleweight and light heavyweight.
Like Fedor, though, he's yet to win gold in a major promotion in the U.S., something that could change for the winner.
There are plenty of good matches to balance out both cards including "Baby Slice" Kevin Ferguson Jr. in action, Roy Nelson vs. Sergei Kharitonov and Benson Henderson vs. Saad Awad.
So, will you tune in and check out the GP semis along with the other action? If so, who do you feel will prevail and fight for the title in 2019? Let us know in the comments section!


Today was a fun day. You wouldn't have known Jackson was here for chemo unless you saw him hooked up to the machine.
Jackson woke up this morning in a great mood. He had a decent appetite and we were able to get a little pancakes and juice into him. After he was done, he wanted to play with Ben (his ipad). We just bought him his own older generation ipad and set it up yesterday. So he was pretty excited to play with his own ipad full of kid movies and apps. However, he didn't want just his ipad, he also wanted Mommy's ipad and iphone. It was hilarious to watch him operating an ipad on each hand while also looking at a video playing on the iphone. After indulging in a morning of sensory overload he went down for a nap.
Jackson's grand parents came to the hospital for the afternoon and I headed home to get some work done. I got back to the hospital around 5 and Jackson was still in a great mood, running around the floor with Tony chasing after him with his IV pole. Around 8, they took Jackson off of his IV and he was a free man for about an hour.
It was the best hour I have had in awhile. Jackson was hilarious, running and dancing around the room to Sesame Street and Tangled music. I haven't seen him so happy and dancing for a long time. Meredith and I both loved it. Jackson you are an amazing little guy, we love you so much and couldn't be more proud of you.