Notes

Interpersonal pet models with regard to quantifying plasticity, collection, as well as assortment upon speaking phenotypes.
DFC analysis within more refined nodes of RSNs showed that OB had more occurrences and a longer MDT in state 1 in which caudate had positive connections with the other network nodes. The findings suggest an association between caudate-related and BG-related positive FC in OB, which was not revealed by traditional FC analysis, highlighting the utility of adding DFC to the more conventional methods.
inequalities and gaps in post-diagnostic support (PDS) for people with dementia persist despite a policy focus on dementia in England and Wales. Understanding and overcoming the factors contributing to these inequalities is vital to improve care for people living with dementia (PLWD) and their families.

to explore common barriers to the delivery of PDS in England and Wales and describe successful strategies to address them, drawing on examples from current practice.

qualitative semi-structured interviews, focus groups and observation.

Phase 1 interviewees were drawn from multiple sectors across England and Wales, including NHS clinical commissioning groups and social care. Phase 2 six case study sites based in different sectors (primary care, secondary mental health and third sector) in England.

Phase 1 61 professionals, including commissioners and service managers. Phase 2 68 professionals, including frontline staff and those working in related services; 17 PLWD; 31 carers.

barriers to implementing PDS in dementia were an unsupportive infrastructure, limited proactive review and limited capacity and capability particularly in primary care. Strategies used successfully in practice to address these challenges included creating opportunities for service development, improving joint working, supporting non-specialists and developing ongoing, holistic review and care planning.

a range of practical strategies have been identified to address many of the common barriers to PDS in dementia. To achieve policy goals of a task-shifted and task-shared approach to PDS, widespread use of these strategies is recommended.
a range of practical strategies have been identified to address many of the common barriers to PDS in dementia. To achieve policy goals of a task-shifted and task-shared approach to PDS, widespread use of these strategies is recommended.
Surgical-site infection (SSI) is a well known complication after breast cancer surgery and has been reported to be associated with cancer recurrence. The aim of this study was to investigate the association between SSI and breast cancer recurrence, adjusting for several known confounders. The secondary aim was to assess a possible association between any postoperative infection and breast cancer recurrence.

This retrospective cohort study included all patients who underwent breast cancer surgery from January 2009 to December 2010 in the Uppsala region of Sweden. Data collected included patient, treatment and tumour characteristics, infection rates and outcome. Association between postoperative infection and oncological outcome was examined using Kaplan-Meier curves and Cox regression analysis.

Some 492 patients (439 with invasive breast cancer) with a median follow-up of 8.4 years were included. Mean(s.d.) age was 62(13) years. Sixty-two (14.1 per cent) of those with invasive breast cancer had an SSI and 43 (9.8 per cent) had another postoperative infection. Some 26 patients had local recurrence; 55 had systemic recurrence. Systemic recurrence was significantly increased after SSI with simple analysis (log rank test, P = 0.035) but this was not observed on adjusted analysis. However, tumour size and lymph node status remained significant predictors for breast cancer recurrence on multiple regression. Other postoperative infections were not associated with recurrence.

Neither SSI nor other postoperative infections were associated with worse oncological outcome in this study. Rather, other factors that relate to both SSI and recurrence may be responsible for the association seen in previous studies.
Neither SSI nor other postoperative infections were associated with worse oncological outcome in this study. Rather, other factors that relate to both SSI and recurrence may be responsible for the association seen in previous studies.Small open reading frames (small ORFs/sORFs/smORFs) are potentially coding sequences smaller than 100 codons that have historically been considered junk DNA by gene prediction software and in annotation screening; however, the advent of next-generation sequencing has contributed to the deeper investigation of junk DNA regions and their transcription products, resulting in the emergence of smORFs as a new focus of interest in systems biology. Several smORF peptides were recently reported in noncanonical mRNAs as new players in numerous biological contexts; however, their relevance is still overlooked in coding potential analysis. Hence, this review proposes a smORF classification based on transcriptional features, discussing the most promising approaches to investigate smORFs based on their different characteristics. First, smORFs were divided into nonexpressed (intergenic) and expressed (genic) smORFs. Second, genic smORFs were classified as smORFs located in noncoding RNAs (ncRNAs) or canonical mRNAs. Finally, smORFs in ncRNAs were further subdivided into sequences located in small or long RNAs, whereas smORFs located in canonical mRNAs were subdivided into several specific classes depending on their localization along the gene. We hope that this review provides new insights into large-scale annotations and reinforces the role of smORFs as essential components of a hidden coding DNA world.
Studies demonstrate an association between visit-to-visit blood pressure variability (BPV) and cardiovascular events and death. We aimed to determine the long-term cardiovascular and mortality effects of BPV in midlife in participants with and without cardiovascular risk factors.

This is a post-hoc analysis of the Atherosclerosis Risk in the Community study. Long-term BPV was derived utilizing mean systolic blood pressure at Visits 1-4 (Visit 1 1987-89, Visit 2 1990-1992, Visit 3 1993-95, Visit 4 1996-98). The primary outcome was mortality from Visit 4 to 2016 and secondary outcome was cardiovascular events (fatal coronary heart disease, myocardial infarction, cardiac procedure, or stroke). We fit Cox proportional hazards models and also performed the analysis in a subgroup of cardiovascular disease-free patients without prior stroke, myocardial infarction, congestive heart failure, hypertension, or diabetes.

We included 9,578 participants. The mean age at the beginning of follow-up was 62.9±5.7 years, and mean follow-up was 14.2±4.5 years. During follow-up, 3,712 (38.8%) participants died and 1,721 (n=8,771, 19.6%) had cardiovascular events. For every standard deviation higher in systolic residual standard deviation (range 0-60.5mm Hg, standard deviation = 5.6mm Hg), the hazard ratio for death was 1.09 (95% CI 1.05-1.12) and for cardiovascular events was 1.00 (95% CI 0.95-1.05). In the subgroup of cardiovascular disease-free participants (n=4,452), the corresponding hazard ratio for death was 1.12 (95% CI 1.03-1.21) and for cardiovascular events was 1.01 (95% CI 0.89-1.14).

Long-term BPV during midlife is an independent predictor of later life mortality but not cardiovascular events.
Long-term BPV during midlife is an independent predictor of later life mortality but not cardiovascular events.
The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data.

Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Suberoylanilide hydroxamic acid Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS).

Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219) months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P < 0.001). Cox regression analyses showed ypN+ status to be an independent predictor of recurrence and death.

Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.
Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.The diversity of cognitive deficits and neuropathological processes associated with dementias has encouraged divergence in pathophysiological explanations of disease. Here, we review an alternative framework that emphasises convergent critical features of cognitive pathophysiology. Rather than the loss of "memory centres" or "language centres", or singular neurotransmitter systems, cognitive deficits are interpreted in terms of aberrant predictive coding in hierarchical neural networks. This builds on advances in normative accounts of brain function, specifically the Bayesian integration of beliefs and sensory evidence in which hierarchical predictions and prediction errors underlie memory, perception, speech and behaviour. We describe how analogous impairments in predictive coding in parallel neurocognitive systems can generate diverse clinical phenomena, including the characteristics of dementias. The review presents evidence from behavioural and neurophysiological studies of perception, language, memory and decision-making. The re-formulation of cognitive deficits in terms of predictive coding has several advantages. It brings diverse clinical phenomena into a common framework; it aligns cognitive and movement disorders; and it makes specific predictions on cognitive physiology that support translational and experimental medicine studies. The insights into complex human cognitive disorders from the predictive coding framework may therefore also inform future therapeutic strategies.
Automated protein function prediction is a complex multi-class, multi-label, structured classification problem in which protein functions are organized in a controlled vocabulary, according to the Gene Ontology (GO). "Hierarchy-unaware" classifiers, also known as "flat" methods, predict GOterms without exploiting the inherent structure of the ontology, potentially violating the True-Path-Rule (TPR) that governs the GO, while "hierarchy-aware" approaches, even if they obey the TPR, do not always show clear improvements with respect to flat methods, or do not scale well when applied to the full GO.

To overcome these limitations, we propose Hierarchical Ensemble Methods for Directed Acyclic Graphs (HEMDAG), a family of highly modular hierarchical ensembles of classifiers, able to build upon any flat method and to provide "TPR-safe" predictions, by leveraging a combination of isotonic regression and TPRlearning strategies. Extensive experiments on synthetic and real data across several organisms firstly show that HEMDAGcan be used as a general tool to improve the predictions of flat classifiers, and secondly that HEMDAGis competitive versus state-of-the-art hierarchy-aware learning methods proposed in the last CAFAinternational challenges.
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