T-cell subset abnormalities predict progression along the Inflammatory Arthritis disease continuum: implications for management

The presence of a disease continuum in inflammatory arthritis (IA) is a recognised concept, with distinct stages from at-risk stage (presence of anti citrullinated-peptide autoantibody) to diagnosis of rheumatoid arthritis (RA), including therapy-induced remission. Despite T-cell dysregulation being a key feature of RA, there are few reports of T-cell phenotyping along the IA-continuum. We investigated the disturbances of naïve, regulatory and inflammation related cell (IRC) CD4+ T-cell subsets in 705 individuals across the IA-continuum, developing a simple risk-score (summing presence/absence of a risk-associated with a subset) to predict progression from one stage to the next. In 158 at-risk individuals, the 3 subsets had individual association with progression to IA and the risk-score was highly predictive (p < 0.0001). In evolving IA patients, 219/294 developed RA; the risk-score included naïve and/or Treg and predicted progression (p < 0.0001). In 120 untreated RA patients, the risk-score for predicting treatment-induced remission using naïve T-cells had an odds ratio of 15.4 (p < 0.0001). In RA patients in treatment-induced remission, a score using naïve T-cells predicted disease flare (p < 0.0001). Evaluating the risk of progression using naïve CD4+ T-cells was predictive of progression along the whole IA-continuum. This should allow identification of individuals at high-risk of progression, permitting targeted therapy for improved outcomes

The branchial Hox code and its implications for gene regulation, patterning of the nervous system and head evolution

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Terahertz underdamped vibrational motion governs protein-ligand binding in solution

Low-frequency collective vibrational modes in proteins have been proposed as being responsible for efficiently directing biochemical reactions and biological energy transport. However, evidence of the existence of delocalized vibrational modes is scarce and proof of their involvement in biological function absent. Here we apply extremely sensitive femtosecond optical Kerr-effect spectroscopy to study the depolarized Raman spectra of lysozyme and its complex with the inhibitor triacetylchitotriose in solution. Underdamped delocalized vibrational modes in the terahertz frequency domain are identified and shown to blue-shift and strengthen upon inhibitor binding. This demonstrates that the ligand-binding coordinate in proteins is underdamped and not simply solvent-controlled as previously assumed. The presence of such underdamped delocalized modes in proteins may have significant implications for the understanding of the efficiency of ligand binding and protein–molecule interactions, and has wider implications for biochemical reactivity and biological function

Interactivity Mitigates the Impact of Working Memory Depletion on Mental Arithmetic Performance

Doing long sums in the absence of complementary actions or artefacts is a multi-step procedure that quickly taxes working memory; congesting the phonological loop further handicaps performance. In the experiment reported here, participants completed long sums either with hands down?the low interactivity condition?or by moving numbered tokens?the high interactivity condition?while they repeated ?the? continuously, loading the phonological loop, or not. As expected, interactivity and articulatory suppression substantially affected performance; critically, the effect of articulatory suppression was stronger in the low than in the high interactivity condition. In addition, independent measure of mathematics anxiety predicted the impact of articulatory suppression on performance only in the low (not high) interactivity condition. These findings suggest that interactivity augmented overall or systemic working memory resources and diminished the effect of mathematics anxiety, underscoring the importance of characterizing the properties of the system as it is configured by the dynamic agent-environment coupling

Breast cancer in lesbians and bisexual women: Systematic review of incidence, prevalence and risk studies

This article is made available through the Brunel Open Access Publishing Fund. © 2013 Meads and Moore; 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 cited.Background: The UK Parliamentary Enquiry and USA Institute of Medicine state that lesbians may be at a higher risk of breast cancer but there is insufficient information. Lesbians and bisexual (LB) women have behavioural risk-factors at higher rates compared to heterosexuals such as increased alcohol intake and higher stress levels. Conversely, breast cancer rates are higher in more affluent women yet income levels in LB women are relatively low. This systematic review investigated all evidence on whether there is, or likely to be, higher rates of breast cancer in LB women. Methods: Cochrane library (CDSR, CENTRAL, HTA, DARE, NHSEED), MEDLINE, EMBASE, PsychINFO, CAB abstracts, Web of Science (SCI, SSCI), SIGLE and Social Care Online databases were searched to October 2013. Unpublished research and specific lesbian, gay and bisexual websites were checked, as were citation lists of relevant papers. Included were studies in LB populations reporting breast cancer incidence or prevalence rates, risk model results or risk-factor estimates. Inclusions, data-extraction and quality assessment were by two reviewers with disagreements resolved by discussion. Results: Searches found 198 references. No incidence rates were found. Nine studies gave prevalence estimates - two showed higher, four showed no differences, one showed mixed results depending on definitions, one had no comparison group and one gave no sample size. All studies were small with poor methodological and/or reporting quality. One incidence modelling study suggested a higher rate. Four risk modelling studies were found, one Rosner-Colditz and three Gail models. Three suggested higher and one lower rate in LB compared to heterosexual women. Six risk-factor estimates suggested higher risk and one no difference between LB and heterosexual women. Conclusions: The only realistic way to establish rates in LB women would be to collect sexual orientation within routine statistics, including cancer registry data, or from large cohort studies

Further development of the Children’s Mathematics Anxiety Scale UK (CMAS-UK) for ages 4–7 years

There are currently many mathematics anxiety rating scales designed typically for adult and older children populations, yet there remains a lack of assessment tools for younger children ( 0.45) and high internal consistency (α = 0.88). A single factor model of Online Mathematics Anxiety was related to the experience of an entire mathematics lesson, from first entering the classroom to completing a task. A significant negative correlation was observed between the CMAS-UK and mathematics performance scores, suggesting that children who score high for mathematics anxiety tend to score to perform less well on a mathematics task. Subsequent confirmatory factor analysis was conducted to test a range of module structures; the shortened 19-item CMAS-UK was found to have similar model indices as the 26-item model, resulting in the maintenance of the revised scale. To conclude, the 19-item CMAS-UK provides a reliable assessment of children’s mathematics anxiety and has been shown to predict mathematics performance. This research points towards the origins of mathematics anxiety occurring when number is first encountered and supports the utility of the CMAS-UK. Subsequent research in the area should consider and appropriately define an affective component that may underlie mathematics anxiety at older ages. Mathematics anxiety relates to more complex procedures that elude the experiences of younger children and may instead be the result of number-based experiences in the early years of education.N/

Statewide Systematic Evaluation of Sudden, Unexpected Infant Death Classification: Results from a National Pilot Project

The Centers for Disease Control and Prevention funded seven states, including Kentucky, to clarify statewide death certification practices in sudden, unexpected infant death and compare state performances with national expectations. Accurate assignment of the cause and manner of death in cases of sudden, unexpected infant death is critical for accurate vital statistics data to direct limited resources to appropriate targets, and to implement optimal and safe risk reduction strategies. The primary objectives are to (1) Compare SUID death certifications recommended by the KY medical examiners with the stated cause of death text field on the hard copy death electronic death certificates and (2) Compare KY and national SUID rates. Causes of death for SUID cases recommended by the medical examiners and those appearing on the hard copy and electronic death certificates in KY were collected retrospectively for 2004 and 2005. Medical examiner recommendations were based upon a classification scheme devised by them in 2003. Coroners hard copy death certificates and the cause of death rates in KY were compared to those occurring nationally. Eleven percent of infants dying suddenly and unexpectedly did not undergo autopsy during the study interval. The KY 2003 classification scheme for SIDS is at variance with the NICHD and San Diego SIDS definitions. Significant differences in causes of death recommended by medical examiners and those appearing on the hard copy and electronic death certificates were identified. SIDS rates increased in KY in contrast to decreasing rates nationally. Nationwide adoption of a widely used SIDS definition, such as that proposed in San Diego in 2004 as well as legislation by states to ensure autopsy in all cases of sudden unexpected infant death are recommended. Medical examiners’ recommendations for cause of death should appear on death certificates. Multidisciplinary pediatric death review teams prospectively evaluating cases before death certification is recommended. Research into other jurisdictions death certification process is encouraged

Negative phenotypic and genetic associations between copulation duration and longevity in male seed beetles

Reproduction can be costly and is predicted to trade-off against other characters. However, while these trade-offs are well documented for females, there has been less focus on aspects of male reproduction. Furthermore, those studies that have looked at males typically only investigate phenotypic associations, with the underlying genetics often ignored. Here, we report on phenotypic and genetic trade-offs in male reproductive effort in the seed beetle, Callosobruchus maculatus. We find that the duration of a male's first copulation is negatively associated with subsequent male survival, phenotypically and genetically. Our results are consistent with life-history theory and suggest that like females, males trade-off reproductive effort against longevity