Distress Tolerance as a Mechanism Linking Violence Exposure to Problematic Alcohol use in Adolescence

Adolescents exposed to violence are at elevated risk of developing most forms of psychopathology, including depression, anxiety, and alcohol abuse. Prior research has identified emotional reactivity and difficulties with emotion regulation as core mechanisms linking violence exposure with psychopathology. Scant research has examined behavioral responses to distress as a mechanism in this association. This study examined the association of violence exposure with distress tolerance—the ability to persist in the face of distress—and whether lower distress tolerance linked violence exposure with subsequent increases in depression, anxiety, and alcohol abuse problems during adolescence. Data were collected prospectively in a sample of 287 adolescents aged 16–17 (44.3% male; 40.8% White). At Time 1, participants provided self-report of demographics, violence exposure, and psychopathology, and completed a behavioral measure of distress tolerance, the Paced Auditory Serial Addition Task. Four months later, participants (n = 237) repeated the psychopathology assessments. Violence exposure was associated with lower distress tolerance (β = -.21 p =.009), and elevated concurrent psychopathology (β =.16-.45, p =.001-.004). Low distress tolerance was prospectively associated with greater likelihood of abusing alcohol over time (OR =.63, p =.021), and mediated the association between violence exposure and greater levels (β =.02, 95% CI [.001,.063]) and likelihood (OR =.03, 95% CI [.006,.065]) of alcohol use over time. In contrast, low distress tolerance was not associated concurrently or prospectively with internalizing symptoms. Results persisted after controlling for socio-economic status. Findings suggest that distress tolerance is shaped by early experiences of threat and plays a role in the association between violence exposure and development of problematic alcohol use in adolescence

Challenges in developing and implementing international best practice guidance for intermediate-risk variants in cancer susceptibility genes:APCc.3920T>A p.(Ile1307Lys) as an exemplar

Published version, accepted version, submitted versionRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted

Long acting progestogens versus combined oral contraceptive pill for preventing recurrence of endometriosis related pain : the PRE-EMPT pragmatic, parallel group, open label, randomised controlled trial

Peer reviewe

The English National Lynch Syndrome transformation project: an NHS Genomic Medicine Service Alliance (GMSA) programme

Objective: In England, through the Genomic Medicine Service Alliances (GMSAs), a national transformation project aims to embed robust pathways to deliver universal Lynch syndrome (LS) testing for patients with colorectal and endometrial cancers. Prior to commencement of the project, there was evidence of variation and low testing levels in eligible patients which is consistent with other health systems; however, we believe this is amenable to systematic improvement with responsibility for testing delivery by local cancer teams supported by regional infrastructure. Methods and analysis: A project team and national oversight group was formed in May 2021 with membership including 21×cancer alliances, 7×GMSAs, charities and other stakeholders who agreed key performance indicators. ‘LS champions’ within each cancer team were identified and surveyed. Workforce training focused on effective identification of eligible patients, overcoming barriers and mainstreamed constitutional genetic testing. Comprehensive pathway data analysis was performed in conjunction with the National Disease Registration Service. Results: Survey and baseline testing data illustrated variation, and a disparity between practice and perception, in levels of testing. The main reported barriers related to funding streams and systematic approaches. Multifaceted training programmes were produced to support workforce development. Champions responsible for testing delivery were appointed in >95% of cancer teams. We identified >9000 historically diagnosed LS patients to support ascertainment for a nationally coordinated screening programme. Conclusion: This ongoing transformational project is strongly supported by stakeholders in England. Significant quality improvement has been implemented, facilitating systematic delivery of universal testing for LS nationally and reduction in variation in care

Neuromagnetic Evidence for Early Auditory Restoration of Fundamental Pitch

Background: Understanding the time course of how listeners reconstruct a missing fundamental component in an auditory stimulus remains elusive. We report MEG evidence that the missing fundamental component of a complex auditory stimulus is recovered in auditory cortex within 100 ms post stimulus onset. Methodology: Two outside tones of four-tone complex stimuli were held constant (1200 Hz and 2400 Hz), while two inside tones were systematically modulated (between 1300 Hz and 2300 Hz), such that the restored fundamental (also knows as ‘‘virtual pitch’’) changed from 100 Hz to 600 Hz. Constructing the auditory stimuli in this manner controls for a number of spectral properties known to modulate the neuromagnetic signal. The tone complex stimuli only diverged on the value of the missing fundamental component. Principal Findings: We compared the M100 latencies of these tone complexes to the M100 latencies elicited by their respective pure tone (spectral pitch) counterparts. The M100 latencies for the tone complexes matched their pure sinusoid counterparts, while also replicating the M100 temporal latency response curve found in previous studies. Conclusions: Our findings suggest that listeners are reconstructing the inferred pitch by roughly 100 ms after stimulus onset and are consistent with previous electrophysiological research suggesting that the inferential pitch is perceived i

Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer

OBJECTIVE: Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes.DESIGN: RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants.RESULTS: Fifteen critical RGs are summarised below: RG1: Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2: Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3: Pressing need for prevention trials; RG4: Lack of integration of different prevention approaches; RG5: Lack of optimal strategies for CRC screening; RG6: Lack of effective triage systems for invasive investigations; RG7: Imprecise pathological assessment of CRC; RG8: Lack of qualified personnel in genomics, data sciences and digital pathology; RG9: Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10: Need for novel technologies/interventions to improve curative outcomes; RG11: Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12: Lack of reliable biomarkers to guide stage IV treatment; RG13: Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14: Lack of coordination of CRC research/funding; RG15: Lack of effective communication between relevant stakeholders.CONCLUSION: Prioritising research activity and funding could have a significant impact on reducing CRC disease burden over the next 5 years.</p

Real-Time Detection and Filtering of Radio Frequency Interference On-board a Spaceborne Microwave Radiometer: The CubeRRT Mission

The Cubesat Radiometer Radio frequency interference Technology validation mission (CubeRRT) was developed to demonstrate real-time on-board detection and filtering of radio frequency interference (RFI) for wide bandwidth microwave radiometers. CubeRRT’s key technology is its radiometer digital backend (RDB) that is capable of measuring an instantaneous bandwidth of 1 GHz and of filtering the input signal into an estimated total power with and without RFI contributions. CubeRRT’s on-board RFI processing capability dramatically reduces the volume of data that must be downlinked to the ground and eliminates the need for ground-based RFI processing. RFI detection is performed by resolving the input bandwidth into 128 frequency sub-channels, with the kurtosis of each sub-channel and the variations in power across frequency used to detect non-thermal contributions. RFI filtering is performed by removing corrupted frequency sub-channels prior to the computation of the total channel power. The 1 GHz bandwidth input signals processed by the RDB are obtained from the payload’s antenna (ANT) and radiometer front end (RFE) subsystems that are capable of tuning across RF center frequencies from 6 to 40 GHz. The CubeRRT payload was installed into a 6U spacecraft bus provided by Blue Canyon Technologies that provides spacecraft power, communications, data management, and navigation functions. The design, development, integration and test, and on-orbit operations of CubeRRT are described in this paper. The spacecraft was delivered on March 22nd, 2018 for launch to the International Space Station (ISS) on May 21st, 2018. Since its deployment from the ISS on July 13th, 2018, the CubeRRT RDB has completed more than 5000 hours of operation successfully, validating its robustness as an RFI processor. Although CubeRRT’s RFE subsystem ceased operating on September 8th, 2018, causing the RDB input thereafter to consist only of internally generated noise, CubeRRT’s key RDB technology continues to operate without issue and has demonstrated its capabilities as a valuable subsystem for future radiometry missions

The use of synthetic and natural vitamin D sources in pig diets to improve meat quality and vitamin D content

This study investigated the effects of synthetic and natural sources of vitamin D biofortification in pig diets on pork vitamin D activity and pork quality. One hundred and twenty pigs (60 male, 60 female) were assigned to one of four dietary treatments for a 55 d feeding period. The dietary treatments were (1)50 μg vitamin D₃/kg of feed; (2)50 μg of 25-hydroxvitamin D₃/kg of feed (25-OH-D₃); (3)50 μg vitamin D₂/kg of feed; (4)50 μg vitamin D₂-enriched mushrooms/kg of feed (Mushroom D₂). The pigs offered the 25-OH-D₃ diet exhibited the highest (P < 0.001) serum total 25-hydroxyvitamin D concentration and subsequently exhibited the highest (P < 0.05) Longissimus thoracis (LT) total vitamin D activity. Mushroom D2 and 25-OH-D3 supplementation increased pork antioxidant status. The vitamin D₂-enriched mushrooms improved (P < 0.05) pig performance, carcass weight and LT colour. In conclusion, 25-OH-D₃ is the most successful source for increasing pork vitamin D activity, while Mushroom D2 may be a new avenue to improve animal performance and pork quality

The COMBREX Project: Design, Methodology, and Initial Results

© 2013 Brian P. et al.Prior to the “genomic era,” when the acquisition of DNA sequence involved significant labor and expense, the sequencing of genes was strongly linked to the experimental characterization of their products. Sequencing at that time directly resulted from the need to understand an experimentally determined phenotype or biochemical activity. Now that DNA sequencing has become orders of magnitude faster and less expensive, focus has shifted to sequencing entire genomes. Since biochemistry and genetics have not, by and large, enjoyed the same improvement of scale, public sequence repositories now predominantly contain putative protein sequences for which there is no direct experimental evidence of function. Computational approaches attempt to leverage evidence associated with the ever-smaller fraction of experimentally analyzed proteins to predict function for these putative proteins. Maximizing our understanding of function over the universe of proteins in toto requires not only robust computational methods of inference but also a judicious allocation of experimental resources, focusing on proteins whose experimental characterization will maximize the number and accuracy of follow-on predictions.COMBREX is funded by a GO grant from the National Institute of General Medical Sciences (NIGMS) (1RC2GM092602-01).Peer Reviewe