Suchergebnisse

Context. DNA extracted non-invasively from remotely collected scat samples has been used successfully to enumerate populations of a few endangered mammal species. However, scat DNA surveys relying on scent-marking behaviours need to identify if age- or sex-specific variations or seasonal changes in scat scent-marking patterns affect population estimates. Furthermore, owing to the low quantity and quality of scat DNA, a thorough assessment of the technique is needed when it is applied to different species to ensure that individual identification is reliable. Aims. In the current study, microsatellite genetic profiles derived from 208 remotely collected scats of the spotted-tailed quoll (Dasyurus maculatus), a rare Australian marsupial carnivore, were compared with DNA profiles from tissue of 22 live-trapped individuals from the same study area to critically assess the reliability of the non-invasive method to estimate population abundance. Methods. Scat samples were collected at scent-marking sites over 4 consecutive months (April–July 2005), 7 weeks of which overlapped with the trapping program to allow direct comparisons of population estimates. Key results. Combining a multiple-tubes approach with error checking analyses provided reliable genetic tags and resulted in the detection of the majority of the live-trapped population (18 of 22 individuals). Ten additional individuals not known from trapping were also observed from scat DNA. A longer-term sampling regime was required for scats than for trapping to allow direct detection of a large proportion of the population and to provide a comparable population estimate. Critically, the 4-month scat collection period highlighted the importance of performing scat surveys during the mating season when scat scent marking is more frequent, and to avoid sex and age biases in scat marking patterns. Implications. Non-invasive scat DNA sampling methods that rely on scent-marking behaviours need to consider the duration of the sampling period and temporal differences in behaviours by the sexes and age groups to ensure that meaningful population estimates are achieved.

Background'Gold-standard' data to evaluate linkage algorithms are rare. Synthetic data have the advantage that all the true links are known. In the domain of population reconstruction, the ability to synthesize populations on demand, with varying characteristics, allows a linkage approach to be evaluated across a wide range of data. We have implemented ValiPop, a microsimulation model, for this purpose.
ApproachValiPop can create many varied populations based upon sets of desired population statistics, thus allowing linkage algorithms to be evaluated across many populations, rather than across a limited number of real world 'gold-standard' data sets.
Given the potential interactions between different desired population statistics, the creation of a population does not necessarily imply that all desired population statistics have been met. To address this we have developed a statistical approach to validate the adherence of created populations to the desired statistics, using a generalized linear model.
This talk will discuss the benefits of synthetic data for data linkage evaluation, the approach to validating created populations, and present the results of some initial linkage experiments using our synthetic data.

Introduction: In the current mobility and globalization context, there is a growing need to identify potential changes on the pattern of diseases in the European Union (EU)/European Economic Area (EEA) and provide accurate diagnosis and treatment for the population. The pattern of rare communicable diseases that can affect people returning to EU/EEA from travel abroad, visiting EU/EEA or establishing in the EU/EEA is of special relevance. The objective of this manuscript is to give an overview about the EURaDMoG study and discuss the feasibility of establishing a European network on rare communicable diseases and other rare conditions linked to mobility and globalization. Methods: We undertook a three-steps process where we first conducted a narrative review to estimate the prevalence and incidence and to list rare communicable and non-communicable diseases linked to mobility and globalization in the EU/EEA; second, we organized an international consultation workshop with experts in the diseases previously selected; and finally, the feasibility study analysed how successful a European expert network on rare diseases linked to mobility and globalization focused on health care provision would be, accounting for different operational and also sustainability criteria. Results: First, considering the areas or topics that the network should cover, it was concluded that communicable and non-communicable rare diseases linked to mobility and globalization should be differentiated. Second, since all non-communicable rare diseases linked to mobility and globalization identified are already covered by different European Reference Networks (ERNs), there is no need for them to be included in a new European network. Three scenarios were considered for establishing a potential European network for rare communicable diseases linked to Mobility and Globalisation with a focus on Health Care provision: 1) To maintain the current situation "Status Quo" scenario; 2) to create a specific European expert network (EEN) on rare ...

The third time wasn't the charm for Republican Second
Circuit Court of Appeals Judge Jeff Cox,
but don't count him out entirely for career advancement in a couple of years.

Late last year, the Bossier Parish-based Cox began
campaigning in earnest for the Second District of the Louisiana Supreme Court,
as incumbent GOP Assoc. Justice Scott Chrichton
faced retirement at the end of this year. He loaned himself $250,000
and spent nearly $16,000 on mailing out postcards to the district as a soft
introduction to his campaign during the Christmas season.

However, one guy that won't be getting holidays
greetings from Cox in the future will be Republican Gov. Jeff Landry. Newly
in office, Landry immediately stumped for reapportionment of the Court not only
to bring roughly uniform population numbers to each district – the map then used
had wildly differing amounts in each district, although this is not a legal nor
constitutional violation – but to create two majority-minority districts. While
nothing juridically required that – even as special interests were suing the state
to produce this outcome that under current jurisprudence had little chance of
success but which would cost the state to defend – theoretically it would give
the state ammunition to have the consent decree in Chisom v. Roemer
lifted, another longtime goal of Landry's currently awaiting a U.S. Fifth
Circuit appellate court hearing.

Twice
this failed, but in the current regular session of the Legislature it finally
succeeded passing a bill accomplishing
these objectives and made it the first act from it, signed by Landry
last week (to exactly zero independent coverage in the media).This new map
finally succeeded by preserving district boundaries of existing Court members
whose terms end in 2026 and beyond, by creating as the new M/M district the
Second.

Although not all sitting justices can run for
reelection, given the Constitution's mandatory retirement age of 70 or older at
the time of inauguration of a term, the arrangement assures that all meet the residency
requirement to stay eligible to serve in their districts until the next
election whether they must retire then. That's bad news for Cox, and to a
lesser degree GOP Assoc. Justice Jay McCallum because
the new map puts Cox in McCallum's Fourth District while the new Second District
starts in East Baton Rouge and goes up the Mississippi River to the Arkansas
border while shooting out fingers up the Red over to the Ouachita Rivers.

Worse for Cox, most of the new Fourth was McCallum's
old Fourth, taking just Bossier, Webster, and small slices of Caddo Parishes
from the old
Second while losing some eastern parishes. Worst of all, and the final insult for
Cox is McCallum's seat comes up for election in 2026 when McCallum can run for reelection,
at the same time Cox's circuit court seat requires an election, and regardless
of which seat Cox contests it would be his final term due to the age
limitation. But had he been able to run for a Court seat this year, he would
have been eligible to run again for that in 2034. This new map basically halves
Cox's eligible time to serve as a jurist and makes him choose his final term as
either a safe seat on the Second Circuit or going for broke for one term on the
Court.

Of course, Cox
has battled victoriously as a challenger. He gained his present seat by
knocking off an incumbent – an almost-unheard-of political outcome for a
judicial race in Louisiana, and especially at the circuit or Supreme Court
level which is why prospects gun for open seats. In that contest, he spent (or
had spent on his behalf; technically, judges can't campaign on their own
behalf) approaching a half-million dollars, or several times his opponent.
McCallum basically has
zippo in his campaign account, so unless he doesn't plan on running again history
tells him he needs to start raising money and fast.

It's been a long time since there's been a
donnybrook between an incumbent and a challenger for the Court. Louisiana might
just get one for the revised Fourth District in two-and-a-half years.

Many pediatric patients with rare diseases use drugs off-label due to limited data in pediatric patients. Off-label treatment remains an important public health issue for neonates, infants, children, and adolescents, especially for pediatric patients with rare diseases. For patients with rare diseases, the majority of medications have no or limited information in labelling for pediatric use. Children present unique considerations in clinical trials due to ethical and clinical concerns, which have limited and even discouraged testing of drugs in the pediatric population. Numerous legislative measures have been enacted to address barriers in pediatric drug testing. This research reviewed off-label medication use in rare pediatric diseases, evaluated recent medication uses in pediatric clinical practice, discussed key regulations for rare pediatric diseases, and summarized recent drug approvals for rare pediatric diseases. This study demonstrates the ongoing medical need for newly approved medications to treat pediatric rare diseases and revealed the positive impact of regulations from the Orphan Drug Act of 1983 to the Research to Accelerate Cures and Equity (RACE) for Children Act on drug development and off-label medication practice in rare pediatric disease management. This article provides informative historical background and current considerations of off-label use of medications in neonates, infants, children, and adolescents with rare diseases.

INTRODUCTION NlmCategory: BACKGROUND content: In the current mobility and globalization context, there is a growing need to identify potential changes on the pattern of diseases in the European Union (EU)/European Economic Area (EEA) and provide accurate diagnosis and treatment for the population. The pattern of rare communicable diseases that can affect people returning to EU/EEA from travel abroad, visiting EU/EEA or establishing in the EU/EEA is of special relevance. The objective of this manuscript is to give an overview about the EURaDMoG study and discuss the feasibility of establishing a European network on rare communicable diseases and other rare conditions linked to mobility and globalization. - Label: METHODS NlmCategory: METHODS content: We undertook a three-steps process where we first conducted a narrative review to estimate the prevalence and incidence and to list rare communicable and non-communicable diseases linked to mobility and globalization in the EU/EEA; second, we organized an international consultation workshop with experts in the diseases previously selected; and finally, the feasibility study analysed how successful a European expert network on rare diseases linked to mobility and globalization focused on health care provision would be, accounting for different operational and also sustainability criteria. - Label: RESULTS NlmCategory: RESULTS content: "First, considering the areas or topics that the network should cover, it was concluded that communicable and non-communicable rare diseases linked to mobility and globalization should be differentiated. Second, since all non-communicable rare diseases linked to mobility and globalization identified are already covered by different European Reference Networks (ERNs), there is no need for them to be included in a new European network. Three scenarios were considered for establishing a potential European network for rare communicable diseases linked to Mobility and Globalisation with a focus on Health Care provision: 1) To maintain the current situation \"Status Quo\" scenario; 2) to create a specific European expert network (EEN) on rare communicable diseases linked to mobility and globalisation; 3) to develop a new ERN on communicable rare diseases linked to mobility and globalisation." - Label: CONCLUSIONS NlmCategory: CONCLUSIONS content: Since the focus is the provision of health care, an ERN could have the potential to better boost the quality of care being facilitated by technological tools and online platforms that permit the safe and ethically acceptable exchange of data. However, this potential new network should not eclipse current existing networks and they should be complementary.

PharmD ; Over 7000 rare diseases (RD) affect around 60 million patients living in the European Union (EU) and the United States (US). Research on RDs focuses on treatment and care of RDs with limited focus on health related quality of life and accessibility to Orphan Drugs (ODs). The aims of this study were to 1) analyse and compare regulations and policies related to accessibility of ODs in the EU and US 2) describe OD accessibility and the health needs of the Maltese RD population and 3) create a health related quality of life (HRQOL) assessment tool for RD patients and caregivers. The HRQOL tool explores issues of diagnosis, mental health, use of health and support services and general quality of life. The methodology included (1) assessment of OD accessibility policies in 29 countries based on 6 themes (national OD policies, OD designation, marketing authorisation, marketing exclusivity, incentives and pricing) identified during retrospective analysis of literature (2) identifying issues encountered by Maltese RD patients by (i) interviewing policy makers (ii) conducting literature review (iii) and analysing data from RD registers (3) development, validation (by 7 experts) and administration of HRQOL tool to patients and caregivers (N=225) in the EU (n=137) and the US (n=88). The tool included 30 close ended Likert scale questions divided into four sections collecting information on the demographics, personal care and independence, mental and social health and access to treatment. The results showed that out of the 29 countries assessed, 17 EU countries had OD policies and 6 countries (including the US) had financial incentives for OD development. OD designation, marketing authorisation and market exclusivity were centralised in both the EU and US by the EMA and FDA respectively. Malta had no OD plans in place and RD patients in Malta had poor access to ODs when compared to other EU countries. Statistical analysis of the HRQOL indicated a significant difference (p<0.05) between RD patients in the EU and US. A significant difference was observed when RD patients were asked to report how they felt during everyday activities such as dressing (p=0.001), eating (p<0.001) or participating in everyday activities (p=0.014) with the US RD patients scoring lower in all areas. The financial burden of RDs was significantly higher (p<0.001) in the US as the Likert mean score was 3.00±1.065 while EU RD patients reported 4.44±0.512 on the Likert scale (1 = Financial burden, 5 Not a burden). Poor OD accessibility was reported by both groups with 44 (32%) EU respondents and 27 (31%) US respondents reporting it is 'almost impossible' to receive treatments for their RD. EMA has granted 140 ODs with market authorisation compared to 415 approved ODs in the US. There are differences between countries on the degree of accessibility, pricing and reimbursement. Poor HRQOL may be related to issues of accessing medicines, diagnosis, psychosocial support, and coping with stigma and uncertainty. US based RD patients scored poorly when compared with their EU counterparts in relation to mental health, personal care and independence and ability to afford ODs. ; N/A

Rare diseases have a prevalence of lower than 5 in 10,000 inhabitants and are life-threatening or chronically debilitating. It is estimated that worldwide more than 5000 rare diseases exist, which account for over 55 million patients in the EU and the US together. However, the development of drugs for rare diseases, so called orphan drugs has not been an area of high priority for the pharmaceutical industry so far. Therefore, dedicated orphan drug legislation has been introduced that aims to stimulate the development of these high medical need products. This thesis identifies strategies for enhancing the development and marketing of orphan drugs. In the first chapter, bottlenecks and opportunities for translating biomedical research on rare diseases into early orphan drug development were studied. This chapter highlighted the importance of basic biomedical research for orphan drug development. Moreover, the studies determined the importance of strong pharmaceutical innovation in general, including patent applications, R&D expenditure and the existence of small and medium enterprises in the pharmaceutical industry, for the successful translation of biomedical research into orphan drug development. The second chapter focussed on characteristics of orphan drugs associated with a positive or negative outcome of the marketing authorisation application (by the FDA or EMEA). First, sponsors with prior experience in (orphan) drug development were more likely to develop another orphan drug. Orphan drugs based on existing molecules had also more chance to get market approval. Second, the choice of the target population for the orphan drug and the choice of the primary endpoint in the pivotal clinical trial was determined to be associated with the outcome of the regulatory assessment. Finally, a higher level of interaction between sponsors and regulators was shown to be positively associated with successful market authorisation. The third chapter of the thesis described the challenges of orphan drugs after approval. As ...

For survey methodologists, latent class analysis (LCA) is a powerful tool for assessing the measurement error in survey questions, evaluating survey methods, and estimating the bias in estimates of population prevalence. LCA can be used when gold standard measurements are not available and applied to essentially any set of indicators that meet certain criteria for identifiability. LCA offers quality inference, provided the key threat to model validity—namely, local dependence—can be appropriately addressed either in the study design or in the model-building process. Three potential causes threaten local independence: bivocality, behaviorally correlated error, and latent heterogeneity. In this article, these threats are examined separately to obtain insights regarding (a) questionnaire designs that reduce local dependence, (b) the effects of local dependence on parameter estimation, and (c) modeling strategies to mitigate these effects in statistical inference. The article focuses primarily on the analysis of rare and sensitivity outcomes and proposes a practical approach for diagnosing and mitigating model failures. The proposed approach is empirically tested using real data from a national survey of inmate sexual abuse where measurement errors are a serious concern. Our findings suggest that the proposed modeling strategy was successful in reducing local dependence bias in the estimates, but its success varied by the quality of the indicators available for analysis. With only three indicators, the biasing effects of local dependence can usually be reduced but not always to acceptable levels.

Abstract Coronary artery disease is a leading cause of death among the aging members of the general population. Treatment strategies addressing the well defined risk factors and genetic factors and which prevent and reduce arterial vascular disease have been established. As in the general population, the prevalence of coronary artery disease also increases with age among adults with intellectual disability (ID), presumably due to the same risk factors. Within the ID population, however, there is a subgroup of individuals with ID due to rare syndromes who are predisposed to premature arteriosclerosis. Hypertension, diabetes mellitus, obesity, hyperhomocysteinemia, and structural arterial abnormalities appear to be associated with these syndromes predisposing them to the early development of widespread vascular disease. Reviewed are the associations between the development of premature arteriosclerosis and rare syndromes of ID. Awareness of the associations may lead to the development of more focused preventive healthcare plans among these groups of individuals.