JURNAL AGROTEKNOLOGI
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Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
No full textIrritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS
TBX2 controls a proproliferative gene expression program in melanoma
No full textSenescence shapes embryonic development, plays a key role in aging, and is a critical barrier to cancer initiation, yet how senescence is regulated remains incompletely understood. TBX2 is an antisenescence T-box family transcription repressor implicated in embryonic development and cancer. However, the repertoire of TBX2 target genes, its cooperating partners, and how TBX2 promotes proliferation and senescence bypass are poorly understood. Here, using melanoma as a model, we show that TBX2 lies downstream from PI3K signaling and that TBX2 binds and is required for expression of E2F1, a key antisenescence cell cycle regulator. Remarkably, TBX2 binding in vivo is associated with CACGTG E-boxes, present in genes down-regulated by TBX2 depletion, more frequently than the consensus T-element DNA binding motif that is restricted to Tbx2 repressed genes. TBX2 is revealed to interact with a wide range of transcription factors and cofactors, including key components of the BCOR/PRC1.1 complex that are recruited by TBX2 to the E2F1 locus. Our results provide key insights into how PI3K signaling modulates TBX2 function in cancer to drive proliferation
What is the thing called the PAS? Metal-detecting entanglements in England and Wales
No full textThe Portable Antiquities Scheme (PAS) was established in 1997 to record metal-detecting and other chance finds of antiquities in England and Wales and to make them available for scholarly study. Other technologies and policies have worked synergistically with the PAS to realise the research potential of its recorded antiquities, but the PAS itself is still open to criticism because of the recalcitrant problem of unreported finds. Alongside the PAS, over the same time period, the Internet market in antiquities grew to become a major commercial outlet for metal-detecting finds. Ian Hodder’s theory of entanglement allows some sense to be made of these recent developments and their impacts upon the research and metal-detecting communities
Chemoprophlaxis trial designs in epidemics: insights from a systematic review of COVID-19 study registrations
No full textBackground
Chemoprophylactics against emerging epidemic and pandemic infectious diseases offer potential for prevention but require efficacy and safety analysis before widespread use can be recommended. Chemoprophylaxis with repurposed drugs enable deployment ahead of development of novel vaccines. It may have particular utility as a stopgap ahead of vaccine deployment or when vaccines become less effective on virus variants, in countries where there may be structural inaccessibility to vaccines, or in specific risk-groups.
Rapid implementation of robust trial designs is a persistent challenge in epidemics. We systematically reviewed SARS-CoV-2 and Covid-19 chemoprophylaxis trial registrations from the first 21 weeks of the pandemic to critically appraise significant design features, alignment of study populations to clinical and public-health uses, and describe candidate chemoprophylactic agents.
Methods
We searched online international trial databases from 31 Dec 2019 to 26 May 2020 using keywords “proph*” or “prevention”. Trial protocols assessing efficacy of chemoprophylactic agents for COVID-19 were included. Trial components were screened for eligibility and relevant studies extracted. Key trial design features were assessed.
Results
We found 76 chemoprophylaxis study registrations, proposing enrolment of 208,367 people with median size of 490. (IQR 262 – 1710). A randomised design was specified for 63 trials, 61 included a control group and total proposed enrolment size was 197,010, median 600 (IQR 236-1834).
Four protocols provide information on effect size sought. We estimate that for a control group attack rate of 10%, 66% of trials would be underpowered to detect a 50% effect size, and 97% of trials would be underpowered to detect a 30% effect size (at the 80% level). We found evidence of adaptive design in one trial registration only. Laboratory-confirmed infection with or without symptoms was the most common primary outcome. Polymerase chain reaction testing alone was used in 46% of trials, serological testing in 6.6% and 14.5% used both testing methods.
Healthcare workers were the target population in 52/79 (65.8%) trials: 49 pre-exposure prophylaxis (PrEP); 3 post-exposure prophylaxis (PEP). Sixteen trials (20.3%) planned PEP in close contacts. Five studies (6.3%) considered chemoprophylaxis in clinical-risk patients. Older adults were the focus of recruitment in only 3 (3.8%) studies (all long-term care facilities). Two (2.5%) studies of PrEP in the general population included older adults. Hydroxychloroquine was the most common candidate agent in 55/79 trials (69.6%), followed by chloroquine (4/79, 5.0%) and lopinavir/ritonavir (3/79, 3.8%).
Conclusion
Many registered COVID-19 chemoprophylaxis efficacy trials were underpowered to detect clinically meaningful protection at epidemiologically-informed attack rates. This, compounded with the time that has taken to organise these trials as compared to the rapid development of Covid-19 vaccines, has rendered these trials of marginal importance. International coordination mechanisms and collaboration is required to support design of feasible chemoprophylaxis trials, large enough to generate strong evidence, early on in an epidemic using adaptive platform trial designs which allow structured entry and exit of candidate agents, as well as rapid stand-up of trial infrastructure.
Registration
Our protocol is registered at osf.io/vp56
Governing AI-driven health research: are IRBs up to the task?
No full textMany are calling for concrete mechanisms of oversight for health research involving artificial intelligence (AI). In response, institutional review boards (IRBs) are being turned to as a familiar model of governance. Here, we examine the IRB model as a form of ethics oversight for health research that uses AI. We consider the model's origins, analyze the challenges IRBs are facing in the contexts of both industry and academia, and offer concrete recommendations for how these committees might be adapted in order to provide an effective mechanism of oversight for health‐related AI research
Pragmatic recommendations for infection prevention and control practices for healthcare facilities in low- and middle-income countries during the COVID-19 pandemic
No full textInfection prevention and control (IPC) strategies are key in preventing nosocomial transmission of COVID-19. Several commonly used IPC practices are resource-intensive and may be challenging to implement in resource-constrained settings. An international group of healthcare professionals from or with experience in low- and middle-income countries (LMICs) searched the literature for relevant evidence. We report on a set of pragmatic recommendations for hospital-based IPC practices in resource-constrained settings of LMICs. For cases of confirmed or suspected COVID-19, we suggest that patients be placed in a single isolation room, whenever possible. When single isolation rooms are unavailable or limited, we recommend cohorting patients with COVID-19 on dedicated wards or in dedicated hospitals. We also recommend that cases of suspected COVID-19 be cohorted separately from those with confirmed disease, whenever possible, to minimize the risk of patient-to-patient transmission in settings where confirmatory testing may be limited. We suggest that healthcare workers be designated to care exclusively for patients with COVID-19, whenever possible, as another approach to minimize nosocomial spread. This approach may also be beneficial in conserving limited supplies of reusable personal protective equipment (PPE). We recommend that visitors be restricted for patients with COVID-19. In settings where family members or visitors are necessary for caregiving, we recommend that the appropriate PPE be used by visitors. We also recommend that education regarding hand hygiene and donning/doffing procedures for PPE be provided. Last, we suggest that all visitors be screened for symptoms before visitation and that visitor logs be maintained
Internet use during COVID-19 lockdown among young people in low- and middle-income countries: Role of psychological wellbeing
No full textProblematic internet use in adolescents has been shown to significantly increase over the past few years, with COVID-19 pandemic lockdowns reinforcing this phenomena globally. We sought to explore whether problematic internet use in specific countries was related to emotional well-being and importantly whether this is predicted by psychological distress. There is a growing number of studies showing that problematic internet use is increasingly prevalent in countries with emerging economies, however we have yet to find out to what extent other factors are influencing this behaviour in adolescents and young people. This study invited young people from countries such India, Mexico, Philippines and Turkey to complete a set of self-reports on their daily internet habits, social media use, alongside questions on psychological distress, self-esteem, loneliness and escapism. A total of 1182 young people aged between 16 and 25 years old completed these questionnaires online. The results showed that there were significant difference in problematic internet use scores among adolescents in the Philippines and Turkey. More specifically, social media use was significantly higher amongst young people from the Philippines whereas gaming addiction was significantly high in the Turkish sample. These findings also revealed that psychological distress, loneliness, and low self-esteem consistently predicted problematic internet use. Taken together these results emphasise that there are several factors underlying growing figures of problematic internet use in young people, these factors include emotional distress, need for escapism, loneliness, and social media use, however, going forward more nuanced cultural differences should also be considered
A multicentre point prevalence survey of patterns and quality of antibiotic prescribing in Indonesian hospitals
No full textBackground
The global emergence of antimicrobial resistance is driven by antibiotic misuse and overuse. However, systematic data in Indonesian hospitals to adequately inform policy are scarce.
Objectives
To evaluate patterns and quality indicators of antibiotic prescribing in six general hospitals in Jakarta, Indonesia.
Methods
We conducted a hospital-wide point prevalence survey (PPS) between March and August 2019, using Global-PPS and WHO-PPS protocols. The analysis focused on antibacterials (antibiotics) for systemic use.
Results
Of 1602 inpatients, 993 (62.0%) received ≥1 antimicrobial. Of 1666 antimicrobial prescriptions, 1273 (76.4%) were antibiotics. Indications comprised community-acquired infections (42.6%), surgical prophylaxis (22.6%), hospital-acquired infections (18.5%), medical prophylaxis (9.6%), unknown (4.6%) and other (2.1%). The most common reasons for antibiotic prescribing were pneumonia (27.7%), skin and soft tissue infections (8.3%), and gastrointestinal prophylaxis (7.9%). The most prescribed antibiotic classes were third-generation cephalosporins (44.3%), fluoroquinolones (13.5%), carbapenems (7.4%), and penicillins with β-lactamase inhibitor (6.8%). According to the WHO AWaRe classification, Watch antibiotics accounted for 67.4%, followed by 28.0% Access and 2.4% Reserve. Hospital antibiotic guidelines were not available for 28.1% of prescriptions, and, where available, guideline compliance was 52.2%. Reason for the antibiotic prescription, stop/review date and planned duration were poorly documented. Culture-guided prescriptions comprised 8.1% of community-acquired infections and 26.8% of hospital-acquired infections.
Conclusions
Our data indicate a high rate of empirical use of broad-spectrum antibiotics in Indonesian hospitals, coupled with poor documentation and guideline adherence. The findings suggest important areas for antimicrobial stewardship interventions
An update on the management of chronic pelvic pain in women
No full textChronic pelvic pain represents a major public health problem for women and impacts significantly on their quality of life. Yet it is under-researched and a challenge to manage. Women who suffer from chronic pelvic pain frequently describe their healthcare journey as long, via a variety of specialists and frustrating, with their pain often dismissed. Aetiological factors and associations are best conceptualised using the 'three P's' model of predisposing, precipitating and perpetuating factors. This integrates the numerous biological, psychological and social contributors to the complex, multifactorial nature of chronic pelvic pain. Overall management involves analgesia, hormonal therapies, physiotherapy, psychological approaches and lifestyle advice, which like other chronic pain conditions relies on a multidisciplinary team approach delivered by professionals experienced and trained in managing chronic pelvic pain
Face memory and face perception in autism
No full textIt has been argued that autistic individuals have difficulties with face memory but typical face perception. However, only one previous study has examined both face memory and face perception in the same individuals, and this study was conducted with a small group of autistic children. Here, face recognition was examined with a group of autistic adults using two face perception tasks (including one designed to avoid a neurotypical bias) and a standard test of face memory. Self-reported face recognition difficulties in everyday life were also recorded. The group of adults with autism scored lower than a matched neurotypical control group on all face tasks and reported more problems with face recognition in everyday life. On the whole, results suggest difficulties with both face perception and face memory in autistic adults, although it should be noted that a wide range of scores were recorded from the autistic individuals, with some scoring in the neurotypical range