Brucellosis remains a neglected disease inthe developing world: a call forinterdisciplinary action

Brucellosis places significant burdens on the human healthcare system and limits the economic growth of individuals, communities, and nations where such development is especially important to diminish the prevalence of poverty. The implementation of public policy focused on mitigating the socioeconomic effects of brucellosis in human and animal populations is desperately needed. When developing a plan to mitigate the associated consequences, it is vital to consider both the abstract and quantifiable effects. This requires an interdisciplinary and collaborative, or One Health, approach that consists of public education, the development of an infrastructure for disease surveillance and reporting in both veterinary and medical fields, and campaigns for control in livestock and wildlife species

Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies

Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point) being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development

The role of mentorship in protege performance

The role of mentorship on protege performance is a matter of importance to academic, business, and governmental organizations. While the benefits of mentorship for proteges, mentors and their organizations are apparent, the extent to which proteges mimic their mentors' career choices and acquire their mentorship skills is unclear. Here, we investigate one aspect of mentor emulation by studying mentorship fecundity---the number of proteges a mentor trains---with data from the Mathematics Genealogy Project, which tracks the mentorship record of thousands of mathematicians over several centuries. We demonstrate that fecundity among academic mathematicians is correlated with other measures of academic success. We also find that the average fecundity of mentors remains stable over 60 years of recorded mentorship. We further uncover three significant correlations in mentorship fecundity. First, mentors with small mentorship fecundity train proteges that go on to have a 37% larger than expected mentorship fecundity. Second, in the first third of their career, mentors with large fecundity train proteges that go on to have a 29% larger than expected fecundity. Finally, in the last third of their career, mentors with large fecundity train proteges that go on to have a 31% smaller than expected fecundity.Comment: 23 pages double-spaced, 4 figure

Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease

IMPORTANCE: The accumulation of aggregated β-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia. Still, to our knowledge, little is known about AD-related myelin changes, and even when present, they are often regarded as secondary to concomitant arteriosclerosis or related to aging. OBJECTIVE: To assess associations between hallmark AD pathology and novel quantitative neuroimaging markers while being sensitive to white matter myelin content. DESIGN, SETTING AND PARTICIPANTS: Magnetic resonance imaging was performed at an academic research neuroimaging center on a cohort of 71 cognitively asymptomatic adults enriched for AD risk. Lumbar punctures were performed and assayed for cerebrospinal fluid (CSF) biomarkers of AD pathology, including β-amyloid 42, total tau protein, phosphorylated tau 181, and soluble amyloid precursor protein. We measured whole-brain longitudinal and transverse relaxation rates as well as the myelin water fraction from each of these individuals. MAIN OUTCOMES AND MEASURES: Automated brain mapping algorithms and statistical models were used to evaluate the relationships between age, CSF biomarkers of AD pathology, and quantitative magnetic resonance imaging relaxometry measures, including the longitudinal and transverse relaxation rates and the myelin water fraction. RESULTS: The mean (SD) age for the 19 male participants and 52 female participants in the study was 61.6 (6.4) years. Widespread age-related changes to myelin were observed across the brain, particularly in late myelinating brain regions such as frontal white matter and the genu of the corpus callosum. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers across brain white matter and in areas preferentially affected in AD. Furthermore, significant age-by-biomarker interactions were observed between myelin water fraction and phosphorylated tau 181/β-amyloid 42, suggesting that phosphorylated tau 181/β-amyloid 42 levels modulate age-related changes in myelin water fraction. CONCLUSIONS AND RELEVANCE: These findings suggest amyloid pathologies significantly influence white matter and that these abnormalities may signify an early feature of the disease process. We expect that clarifying the nature of myelin damage in preclinical AD may be informative on the disease’s course and lead to new markers of efficacy for prevention and treatment trials

A systematic review and meta-synthesis of the impact of low back pain on people's lives

Copyright @ 2014 Froud et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background - Low back pain (LBP) is a common and costly problem that many interpret within a biopsychosocial model. There is renewed concern that core-sets of outcome measures do not capture what is important. To inform debate about the coverage of back pain outcome measure core-sets, and to suggest areas worthy of exploration within healthcare consultations, we have synthesised the qualitative literature on the impact of low back pain on people’s lives. Methods - Two reviewers searched CINAHL, Embase, PsycINFO, PEDro, and Medline, identifying qualitative studies of people’s experiences of non-specific LBP. Abstracted data were thematic coded and synthesised using a meta-ethnographic, and a meta-narrative approach. Results - We included 49 papers describing 42 studies. Patients are concerned with engagement in meaningful activities; but they also want to be believed and have their experiences and identity, as someone ‘doing battle’ with pain, validated. Patients seek diagnosis, treatment, and cure, but also reassurance of the absence of pathology. Some struggle to meet social expectations and obligations. When these are achieved, the credibility of their pain/disability claims can be jeopardised. Others withdraw, fearful of disapproval, or unable or unwilling to accommodate social demands. Patients generally seek to regain their pre-pain levels of health, and physical and emotional stability. After time, this can be perceived to become unrealistic and some adjust their expectations accordingly. Conclusions - The social component of the biopsychosocial model is not well represented in current core-sets of outcome measures. Clinicians should appreciate that the broader impact of low back pain includes social factors; this may be crucial to improving patients’ experiences of health care. Researchers should consider social factors to help develop a portfolio of more relevant outcome measures.Arthritis Research U

Recovery from Posttraumatic Stress Symptoms: A Qualitative Study of Attributions in Survivors of War

This study was funded by a grant from the European Commission, contract number INCO-CT-2004-50917

palaeoverse: A community‐driven R package to support palaeobiological analysis

1. The open-source programming language ‘R' has become a standard tool in the palaeobiologist's toolkit. Its popularity within the palaeobiological community continues to grow, with published articles increasingly citing the usage of R and R packages. However, there are currently a lack of agreed standards for data preparation and available frameworks to support the implementation of such standards. Consequently, data preparation workflows are often unclear and not reproducible, even when code is provided. Moreover, due to a lack of code accessibility and documentation, palaeobiologists are often forced to ‘reinvent the wheel’ to find solutions to issues already solved by other members of the community. 2. Here, we introduce palaeoverse, a community-driven R package to aid data preparation and exploration for quantitative palaeobiological research. The package is freely available and has three core principles: (1) streamline data preparation and analyses; (2) enhance code readability; and (3) improve reproducibility of results. To develop these aims, we assessed the analytical needs of the broader palaeobiological community using an online survey, in addition to incorporating our own experiences. 3. In this work, we first report the findings of the survey, which shaped the development of the package. Subsequently, we describe and demonstrate the functionality available in palaeoverse and provide usage examples. Finally, we discuss the resources we have made available for the community and our future plans for the broader Palaeoverse project. 4. palaeoverse is a community-driven R package for palaeobiology, developed with the intention of bringing palaeobiologists together to establish agreed standards for high-quality quantitative research. The package provides a user-friendly platform for preparing data for analysis with well-documented open-source code to enhance transparency. The functionality available in palaeoverse improves code reproducibility and accessibility, which is beneficial for both the review process and future research

Neuroimaging of tissue microstructure as a marker of neurodegeneration in the AT(N) framework: defining abnormal neurodegeneration and improving prediction of clinical status

Background: Alzheimer’s disease involves accumulating amyloid (A) and tau (T) pathology, and progressive neurodegeneration (N), leading to the development of the AD clinical syndrome. While several markers of N have been proposed, efforts to define normal vs. abnormal neurodegeneration based on neuroimaging have been limited. Sensitive markers that may account for or predict cognitive dysfunction for individuals in early disease stages are critical. Methods: Participants (n = 296) defined on A and T status and spanning the AD-clinical continuum underwent multi-shell diffusion-weighted magnetic resonance imaging to generate Neurite Orientation Dispersion and Density Imaging (NODDI) metrics, which were tested as markers of N. To better define N, we developed age- and sex-adjusted robust z-score values to quantify normal and AD-associated (abnormal) neurodegeneration in both cortical gray matter and subcortical white matter regions of interest. We used general logistic regression with receiver operating characteristic (ROC) and area under the curve (AUC) analysis to test whether NODDI metrics improved diagnostic accuracy compared to models that only relied on cerebrospinal fluid (CSF) A and T status (alone and in combination). Results: Using internal robust norms, we found that NODDI metrics correlate with worsening cognitive status and that NODDI captures early, AD neurodegenerative pathology in the gray matter of cognitively unimpaired, but A/T biomarker-positive, individuals. NODDI metrics utilized together with A and T status improved diagnostic prediction accuracy of AD clinical status, compared with models using CSF A and T status alone. Conclusion: Using a robust norms approach, we show that abnormal AD-related neurodegeneration can be detected among cognitively unimpaired individuals. Metrics derived from diffusion-weighted imaging are potential sensitive markers of N and could be considered for trial enrichment and as outcomes in clinical trials. However, given the small sample sizes, the exploratory nature of the work must be acknowledged

Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults

INTRODUCTION: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. METHODS: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ)42/Aβ40 and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. RESULTS: We observed a significant CSF Aβ42/Aβ40 × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. DISCUSSION: NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment