Grey and white matter differences in Chronic Fatigue Syndrome : A voxel-based morphometry study

Conflicts of interest and source of funding The authors declare no conflicts of interest. This research was funded by the Medical Research Council (MR/J002712/1). AF is supported by Research Capability Funding from the Newcastle upon Tyne Hospitals NHS Foundation Trust and the Northumberland, Tyne and Wear NHS Foundation Trust.Peer reviewedPublisher PD

N-Alkyl-α-amino acids in Nature and their biocatalytic preparation

PWS would like to acknowledge the European Union for his current funding: “This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement No 665919”.N-alkylated-α-amino acids are useful building blocks for the pharmaceutical and fine chemical industries. Enantioselective methods of N-alkylated-α-amino acid synthesis are therefore highly valuable and widely investigated. While there are a variety of chemical methods for their synthesis, they often employ stoichiometric quantities of hazardous reagents such as pyrophoric metal hydrides or genotoxic alkylating agents, whereas biocatalytic routes can provide a greener and cleaner alternative to existing methods. This review highlights the occurrence of the N-alkyl-α-amino acid motif and its role in nature, important applications towards human health and biocatalytic methods of preparation. Several enzyme classes that can be used to access chiral N-alkylated-α-amino acids and their substrate selectivities are detailed.PostprintPeer reviewe

Evaluating Native American Bird Use and Bird Assemblage Variability along the Oregon Coast

Native American use of birds on the Oregon coast is not well known and has never been synthesized to present a regional understanding. We rectify this by analyzing data from 26 zooarchaeological assemblages, including three previously unpublished bird assemblages: Umpqua/Eden (35DO83), Whale Cove (35LNC60), and the Dunes Site (35CLT27). We employ a series of non-parametric randomization tests to directly evaluate patterns of taxonomic diversity, correlations with nearby breeding colonies, and broader procurement strategies discussed in ethnohistorical accounts. We compare the assemblages to contemporary surveys of naturally beached birds as observed by COASST (Coastal Observation Seabird Survey Team) and evaluate whether archaeological specimens were scavenged from the beach. While 71% of the identified bird remains belong to just three families (Anatidae, Alcidae, and Procellariidae), closer analysis reveals the incredible diversity of birds used by Oregon coast Native Americans. The assemblages vary considerably in terms of taxonomic diversity and composition, leading us to conclude that people used birds opportunistically, likely incorporating multiple strategies, including hunting, collecting beached carcasses and targeting cormorant colonies. We hope that the methods and approaches employed here will inspire other archaeologists to devote more attention to bird assemblages, and how their study can inform conservation efforts

Biocatalytic synthesis of chiral N-functionalized amino acids

N-functionalized amino acids are important building blocks for the preparation of diverse bioactive molecules including peptides. The development of sustainable manufacturing routes to chiral N-alkylated amino acids remains a significant challenge in the pharmaceutical and fine chemical industries. Herein we report the discovery of a structurally diverse panel of biocatalysts which catalyze the asymmetric synthesis of N-alkyl amino acids via the reductive coupling of ketones and amines. Reactions have been performed on a gram scale to yield optically pure N-alkyl functionalized products in high yields.PostprintPeer reviewe

Protocol for PD SENSORS:Parkinson’s Disease Symptom Evaluation in a Naturalistic Setting producing Outcomes measuRes using SPHERE technology. An observational feasibility study of multi-modal multi-sensor technology to measure symptoms and activities of daily living in Parkinson’s disease

Introduction The impact of disease-modifying agents on disease progression in Parkinson’s disease is largely assessed in clinical trials using clinical rating scales. These scales have drawbacks in terms of their ability to capture the fluctuating nature of symptoms while living in a naturalistic environment. The SPHERE (Sensor Platform for HEalthcare in a Residential Environment) project has designed a multi-sensor platform with multimodal devices designed to allow continuous, relatively inexpensive, unobtrusive sensing of motor, non-motor and activities of daily living metrics in a home or a home-like environment. The aim of this study is to evaluate how the SPHERE technology can measure aspects of Parkinson’s disease.Methods and analysis This is a small-scale feasibility and acceptability study during which 12 pairs of participants (comprising a person with Parkinson’s and a healthy control participant) will stay and live freely for 5 days in a home-like environment embedded with SPHERE technology including environmental, appliance monitoring, wrist-worn accelerometry and camera sensors. These data will be collected alongside clinical rating scales, participant diary entries and expert clinician annotations of colour video images. Machine learning will be used to look for a signal to discriminate between Parkinson’s disease and control, and between Parkinson’s disease symptoms ‘on’ and ‘off’ medications. Additional outcome measures including bradykinesia, activity level, sleep parameters and some activities of daily living will be explored. Acceptability of the technology will be evaluated qualitatively using semi-structured interviews.Ethics and dissemination Ethical approval has been given to commence this study; the results will be disseminated as widely as appropriate

An investigation into the prevalence of sleep disturbances in primary Sjögren’s syndrome: a systematic review of the literature

Objectives. To identify whether sleep disturbances are more prevalent in primary SS (pSS) patients compared with the general population and to recognize which specific sleep symptoms are particularly problematic in this population. Methods. Electronic searches of the literature were conducted in PubMed, Medline (Ovid), Embase (Ovid), PsychINFO (Ovid) and Web of Science and the search strategy registered a priori. Titles and abstracts were reviewed by two authors independently against a set of prespecified inclusion/exclusion criteria, reference lists were examined and a narrative synthesis of the included articles was conducted. Results. Eight whole-text papers containing nine separate studies met the inclusion criteria and were included in the narrative analysis. Few of these studies met all of the quality assessment criteria. The studies used a range of self-reported measures and objective measures, including polysomnography. Mixed evidence was obtained for some of the individual sleep outcomes, but overall compared with controls, pSS patients reported greater subjective sleep disturbances and daytime somnolence and demonstrated more night awakenings and pre-existing obstructive sleep apnoea. Conclusions. A range of sleep disturbances are commonly reported in pSS patients. Further polysomnography studies are recommended to confirm the increased prevalence of night awakenings and obstructive sleep apnoea in this patient group. pSS patients with excessive daytime somnolence should be screened for co-morbid sleep disorders and treated appropriately. Interventions targeted at sleep difficulties in pSS, such as cognitive behavioural therapy for insomnia and nocturnal humidification devices, have the potential to improve quality of life in this patient group and warrant further investigation

Navigating Identity Uncertainty: Identity Distress During the COVID-19 Pandemic

The long-term effects of the COVID-19 pandemic have only recently begun to be explored. Among college students, who were faced with sudden and unprecedented changes and challenges, it is likely that COVID-19 detrimentally impacted the establishment of a sense of self, a key developmental task of the college years. However, no research has examined the relationships among COVID-19 related worries, identity distress, and psychological and academic adjustment. To address these gaps in the current study, we examined the prevalence of identity distress, the relationship between COVID-19 related worries and identity distress, and the direct and indirect associations between COVID-19 related worries and psychological and academic adjustment among a sample of 1627 college students (M-age = 20.51, SD = 2.21). Findings indicated that over a third of the sample reported high levels of identity distress and that COVID-19 related worries were negatively associated, both directly and indirectly through identity distress, with psychological and academic adjustment

The SNAPSHOT study protocol : SNAcking, Physical activity, Self-regulation, and Heart rate Over Time

Peer reviewedPublisher PD

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care