Taking the LEAP (Learner Engaged Advising Programs): VCCS Advising Practices and Recommendations

The Virginia Community College System (VCCS) administration identified the need for adequate and proactive advising programs to foster student success. This paper presents a review of “best practices” in advising to determine commonalities, provides a comparison with current VCCS advising practices, and offers recommendations that support the goal of ensuring high quality advising programs

DNAAF1 links heart laterality with the AAA+ ATPase RUVBL1 and ciliary intraflagellar transport

DNAAF1 (LRRC50) is a cytoplasmic protein required for dynein heavy chain assembly and cilia motility, and DNAAF1 mutations cause primary ciliary dyskinesia (PCD; MIM 613193). We describe four families with DNAAF1 mutations and complex congenital heart disease (CHD). In three families, all affected individuals have typical PCD phenotypes. However, an additional family demonstrates isolated CHD (heterotaxy) in two affected siblings, but no clinical evidence of PCD. We identified a homozygous DNAAF1 missense mutation, p.Leu191Phe, as causative for heterotaxy in this family. Genetic complementation in dnaaf1-null zebrafish embryos demonstrated the rescue of normal heart looping with wild-type human DNAAF1, but not the p.Leu191Phe variant, supporting the conserved pathogenicity of this DNAAF1 missense mutation. This observation points to a phenotypic continuum between CHD and PCD, providing new insights into the pathogenesis of isolated CHD. In further investigations of the function of DNAAF1 in dynein arm assembly, we identified interactions with members of a putative dynein arm assembly complex. These include the ciliary intraflagellar transport protein IFT88 and the AAA+ (ATPases Associated with various cellular Activities) family proteins RUVBL1 (Pontin) and RUVBL2 (Reptin). Co-localization studies support these findings, with the loss of RUVBL1 perturbing the co-localization of DNAAF1 with IFT88. We show that RUVBL1 orthologues have an asymmetric left-sided distribution at both the mouse embryonic node and the Kupffer’s vesicle in zebrafish embryos, with the latter asymmetry dependent on DNAAF1. These results suggest that DNAAF1-RUVBL1 biochemical and genetic interactions have a novel functional role in symmetry breaking and cardiac development

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

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Personalised risk communication for informed decision making about taking screening tests.

Contains fulltext : 51009.pdf (publisher's version ) (Open Access)BACKGROUND: There is a trend towards greater patient involvement in healthcare decisions. Adequate discussion of the risks and benefits associated with different choices is often required if involvement is to be genuine and effective. Achieving both the adequate involvement of consumers and informed decision making are now seen as important goals for any screening programme. Personalised risk estimates have been shown to be effective methods of risk communication in general, but the effectiveness of different strategies has not previously been examined. OBJECTIVES: To assess the effects of different types of personalised risk communication for consumers making decisions about taking screening tests. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1985 to December 2005), EMBASE (1985 to December 2005), CINAHL (1985 to December 2005), and PsycINFO (1989 to December 2005). Follow-up searches involved hand searching Preventive Medicine, citation searches on seven authors, and searching reference lists of articles. For the original version of this review (Edwards 2003c) we also searched CancerLit (1985 to 2001) and Science Citation Index Expanded (searched March 2002). SELECTION CRITERIA: Randomised controlled trials addressing the decision by consumers of whether or not to undergo screening, incorporating an intervention with a 'personalised risk communication element' and reporting cognitive, affective, or behavioural outcomes. A 'personalised risk communication element' is based on the individual's own risk factors for a condition (such as age or family history). It may be calculated from an individual's risk factors using formulae derived from epidemiological data, and presented as an absolute or relative risk or as a risk score, or it may be categorised into, for example, high, medium or low risk groups. It may be less detailed still, involving a listing, for example, of a consumer's risk factors as a focus for discussion and intervention. DATA COLLECTION AND ANALYSIS: Two authors independently assessed each trial for quality and extracted data. We extracted data about the nature and setting of the intervention, and relevant outcome data, along with items relating to methodological quality. We then used standard statistical methods of the Consumers and Communication Review Group to combine data using MetaView, including analysis according to different levels of detail of personalised risk communication, different condition for screening, and studies based only on high risk participants rather than people at 'average' risk. MAIN RESULTS: Twenty-two studies were included, nine of which were added in the 2006 update of this review. There was weak evidence, consistent with a small effect, that personalised risk communication (whether written, spoken or visually presented) increases uptake of screening tests (odds ratio (OR) 1.31 (random effects, 95% confidence interval (CI) 0.98 to 1.77). In three studies the interventions showed a trend towards more accurate risk perception (OR 1.65 (95% CI 0.96 to 2.81), and three other trials with heterogenous outcome measures showed improvements in knowledge with personalised risk interventions. There was little other evidence from these studies that the interventions promoted or achieved informed decision making by consumers about participation in screening. More detailed personalised risk communication may be associated with a smaller increase in uptake of tests. That is, for personalised risk communication which used and presented numerical calculations of risk, the OR for test uptake was 0.82 (95% CI 0.65 to 1.03). For risk estimates or calculations which were categorised into high, medium or low strata of risk, the OR was 1.42 (95% CI 1.07 to 1.89). For risk communication that simply listed personal risk factors the OR was 1.42 (95% CI 0.95 to 2.12). Over half of the included studies assessed interventions in the context of mammography. These studies showed similar effects to the overall dataset. The five studies examining risk communication in high risk individuals (individuals at higher risk due to, for example, a family history of breast cancer or other conditions) showed larger odds ratios for uptake of tests than the other studies (random effects OR 1.74; 95% CI 1.05 to 2.88). There were insufficient data from the included studies to report odds ratios on other key outcomes such as: intention to take tests, anxiety, satisfaction with decisions, decisional conflict, knowledge and resource use. AUTHORS' CONCLUSIONS: Personalised risk communication (as currently implemented in the included studies) may have a small effect on increasing uptake of screening tests, and there is only limited evidence that the interventions have promoted or achieved informed decision making by consumers

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease