Quantitative analysis of regulatory flexibility under changing environmental conditions

The circadian clock controls 24-h rhythms in many biological processes, allowing appropriate timing of biological rhythms relative to dawn and dusk. Known clock circuits include multiple, interlocked feedback loops. Theory suggested that multiple loops contribute the flexibility for molecular rhythms to track multiple phases of the external cycle. Clear dawn- and dusk-tracking rhythms illustrate the flexibility of timing in Ipomoea nil. Molecular clock components in Arabidopsis thaliana showed complex, photoperiod-dependent regulation, which was analysed by comparison with three contrasting models. A simple, quantitative measure, Dusk Sensitivity, was introduced to compare the behaviour of clock models with varying loop complexity. Evening-expressed clock genes showed photoperiod-dependent dusk sensitivity, as predicted by the three-loop model, whereas the one- and two-loop models tracked dawn and dusk, respectively. Output genes for starch degradation achieved dusk-tracking expression through light regulation, rather than a dusk-tracking rhythm. Model analysis predicted which biochemical processes could be manipulated to extend dusk tracking. Our results reveal how an operating principle of biological regulators applies specifically to the plant circadian clock

Post-traumatic stress disorder following childbirth: an update of current issues and recommendations for future research

Objective: This paper aimed to report the current status of research in the field of post-traumatic stress disorder following childbirth (PTSD FC), and to update the findings of an earlier 2008 paper. Background: A group of international researchers, clinicians and service users met in 2006 to establish the state of clinical and academic knowledge relating to PTSD FC. A paper identified four key areas of research knowledge at that time. Methods: Fourteen clinicians and researchers met in Oxford, UK to update the previously published paper relating to PTSD FC. The first part of the meeting focused on updating the four key areas identified previously, and the second part on discussing new and emerging areas of research within the field. Results: A number of advances have been made in research within the area of PTSD FC. Prevalence is well established within mothers, several intervention studies have been published, and there is growing interest in new areas: staff and pathways; prevention and early intervention; impact on families and children; special populations; and post-traumatic growth. Conclusion: Despite progress, significant gaps remain within the PTSD FC knowledge base. Further research continues to be needed across all areas identified in 2006, and five areas were identified which can be seen as ‘new and emerging’. All of these new areas require further extensive research. Relatively little is still known about PTSD FC

Conditioning laboratory cats to handling and transport

As research subjects, cats have contributed substantially to our understanding of biological systems, from the development of mammalian visual pathways to the pathophysiology of feline immunodeficiency virus as a model for human immunodeficiency virus. Few studies have evaluated humane methods for managing cats in laboratory animal facilities, however, in order to reduce fear responses and improve their welfare. The authors describe a behavioral protocol used in their laboratory to condition cats to handling and transport. Such behavioral conditioning benefits the welfare of the cats, the safety of animal technicians and the quality of feline research data

A Multi-surgeon Robotic-guided Thoracolumbar Fusion Experience: Accuracy, Radiation, Complications, Readmissions, and Revisions of 3,874 Screws across Three Robotic Generations

Objective Robotic guidance provides indirect visualization of key anatomic landmarks to facilitate minimally invasive surgery (MIS) and is emerging as a reliable and accurate technique for posterior spine instrumentation. We sought to describe eight years of experience with robotic guidance at a high-volume, multi-surgeon center. We hypothesize that robotic guidance will lead to (1) low rates of complication, readmissions, and revision surgery, (2) reduced fluoroscopic radiation exposure, (3) and accurate thoracolumbar instrumentation. Methods A retrospective review of complications, revision surgery, and readmission rates in patients undergoing thoracolumbar fusion surgery utilizing three robotic generations. Secondary analysis was conducted comparing the three robotic generations for complications, revision surgery, accuracy, and readmission rates along with intraoperative fluoroscopic duration. Results A total of 628 patients (3,874 robotic-guided screws) ages 12–81 years-old (43.9% male) were included in the study. At one year, the cumulative complication incidence was 15.5% with a 10.3% incidence of surgical complications (3.7% wound, 1.2% robot-related, and 5.4% non-robot-related complications). At one year, the revision surgery incidence was 9.4%. There was no statistical difference between complications, readmission, or revision surgery after initial admission among the three robotic generations. The average intraoperative fluoroscopic duration was 53.8 seconds (11.9 seconds per screw and 17.6 seconds per instrumented level). Conclusion Robotic guidance in thoracolumbar instrumented fusions was associated with low complication, revision surgery, and readmission rates. Our results suggest robotic guidance can provide accurate guidance with minimal adverse events in thoracolumbar instrumentation

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Complete Genome Sequences of Cluster A Mycobacteriophages BobSwaget, Fred313, KADY, Lokk, MyraDee, Stagni, and StepMih

Seven mycobacteriophages from distinct geographical locations were isolated, using Mycobacterium smegmatis mc2155 as the host, and then purified and sequenced. All of the genomes are related to cluster A mycobacteriophages, BobSwaget and Lokk in subcluster A2; Fred313, KADY, Stagni, and StepMih in subcluster A3; and MyraDee in subcluster A18, the first phage to be assigned to that subcluster

Assessing safe and personalised maternity and neonatal care through a pandemic: a case study of outcomes and experiences in two trusts in England using the ASPIRE COVID-19 framework

Background: The COVID-19 pandemic has resulted in profound and far-reaching impacts on maternal and newborn care and outcomes. As part of the ASPIRE COVID-19 project, we describe processes and outcome measures relating to safe and personalised maternity care in England which we map against a pre-developed ASPIRE framework to establish the potential impact of the COVID-19 pandemic for two UK trusts. Methods: We undertook a mixed-methods system-wide case study using quantitative routinely collected data and qualitative data from two Trusts and their service users from 2019 to 2021 (start and completion dates varied by available data). We mapped findings to our prior ASPIRE conceptual framework that explains pathways for the impact of COVID-19 on safe and personalised care. Results: The ASPIRE framework enabled us to develop a comprehensive, systems-level understanding of the impact of the pandemic on service delivery, user experience and staff wellbeing, and place it within the context of pre-existing challenges. Maternity services experienced some impacts on core service coverage, though not on Trust level clinical health outcomes (with the possible exception of readmissions in one Trust). Both users and staff found some pandemic-driven changes challenging such as remote or reduced antenatal and community postnatal contacts, and restrictions on companionship. Other key changes included an increased need for mental health support, changes in the availability and uptake of home birth services and changes in induction procedures. Many emergency adaptations persisted at the end of data collection. Differences between the trusts indicate complex change pathways. Staff reported some removal of bureaucracy, which allowed greater flexibility. During the first wave of COVID-19 staffing numbers increased, resolving some pre-pandemic shortages: however, by October 2021 they declined markedly. Trying to maintain the quality and availability of services had marked negative consequences for personnel. Timely routine clinical and staffing data were not always available and personalised care and user and staff experiences were poorly captured. Conclusions: The COVID-19 crisis magnified pre-pandemic problems and in particular, poor staffing levels. Maintaining services took a significant toll on staff wellbeing. There is some evidence that these pressures are continuing. There was marked variation in Trust responses. Lack of accessible and timely data at Trust and national levels hampered rapid insights. The ASPIRE COVID-19 framework could be useful for modelling the impact of future crises on routine care

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Non-bee insects are important contributors to global crop pollination

Wild and managed bees are well documented as effective pollinators of global crops of economic importance. However, the contributions by pollinators other than bees have been little explored despite their potential to contribute to crop production and stability in the face of environmental change. Non-bee pollinators include flies, beetles, moths, butterflies, wasps, ants, birds, and bats, among others. Here we focus on non-bee insects and synthesize 39 field studies from five continents that directly measured the crop pollination services provided by non-bees, honey bees, and other bees to compare the relative contributions of these taxa. Non-bees performed 25–50% of the total number of flower visits. Although non-bees were less effective pollinators than bees per flower visit, they made more visits; thus these two factors compensated for each other, resulting in pollination services rendered by non-bees that were similar to those provided by bees. In the subset of studies that measured fruit set, fruit set increased with non-bee insect visits independently of bee visitation rates, indicating that non-bee insects provide a unique benefit that is not provided by bees. We also show that non-bee insects are not as reliant as bees on the presence of remnant natural or seminatural habitat in the surrounding landscape. These results strongly suggest that non-bee insect pollinators play a significant role in global crop production and respond differently than bees to landscape structure, probably making their crop pollination services more robust to changes in land use. Non-bee insects provide a valuable service and provide potential insurance against bee population declines