bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized Controlled Feasibility Trial Evaluating a Resistance Training Intervention With Frail Older Adults in Residential Care: The Keeping Active in Residential Elderly Trial
Authors: Swales Bridgitte , Ryde Gemma C. , Whittaker Anna C.
Published: September 2021

Frailty is associated with negative health outcomes, disability, and mortality. Physical activity is an effective intervention to improve functional health status. However, the effect of resistance training on multidimensional health in frail older adults remains unclear. This randomized controlled trial was conducted in a U.K. residential care home to assess feasibility with limited efficacy testing on health and functional outcomes and to inform a future definitive randomized controlled trial. Eleven frail older adults (>65 years) completed a 6-week machine-based resistance training protocol three times a week. Uptake and retention were greater than 80%. The measures and intervention were found to be acceptable and practicable. The analyses indicated large improvements in functional capacity, frailty, and strength in the intervention group compared with the controls. These findings support the feasibility of a definitive randomized controlled trial and reinforce the value of resistance training in this population. This trial was registered with ClinicalTrials.gov: NCT03141879.
Watching Your Neck: The Influence of Real-Time Visual Feedback on Cervical Joint Position Sense in Chronic Neck Pain
Authors: Beinert Konstantin , Deutsch Katharina , Löscher Sebastian , Diers Martin
Published: September 2021

Patients with neck pain demonstrate a variety of sensorimotor impairments, such as decreased cervical joint position sense (CJPS) acuity, which might also be associated with an impaired internal body representation. The present study evaluated the effect of real-time visual feedback of the individual’s own neck on CJPS compared to observing a book. Twenty-three patients with neck pain participated in the experiment and received the interventions in randomized order on separate days in a within-subject pretest–posttest design. Before and immediately after each intervention, CJPS was measured by a therapist blinded to the intervention. The results demonstrate a significantly different development of CJPS (p = .04), with increased CJPS acuity after observing one’s own neck and decreased acuity after observing a book. Real-time visual feedback of the neck improved CJPS acuity in patients with neck pain without active movements of the neck, indicating the importance of central nervous system processing for CJPS acuity.
Match Acceleration and Deceleration Patterns in Female Collegiate Soccer Players
Authors: Trapp Jessica L. , Stannard Alicja B. , Nolan Julie K. , Moran Matthew F.
Published: September 2021

The purpose of the current investigation was to report acceleration and deceleration match data in female collegiate soccer players and compare between positions and game halves. A total of 24 players (11 defenders, five midfielders, and eight forwards) (age: M = 19.1, SD = 1.2 years; height: M = 1.64, SD = 0.05 m; and mass: M = 62.2, SD = 5.8 kg) underwent global positioning system monitoring and performance testing. Forwards covered significantly more distance per minute during high-intensity running (effect size [d]: 0.49) and sprinting (d = 0.64) when compared to midfielders across 16 matches for players logging  22.5 min per half. Significant and meaningful positional differences were determined with forwards covering the greatest average distance per acceleration efforts (d = 0.55) and initiating acceleration and deceleration efforts from a greater initial speed (ds = 0.57 and 0.69). When analyzing across all matches for players logging ≥ 40 min per half, second half decreases occurred in the number of accelerations (p < .001; d = 1.98) and decelerations (p < .001; d = 1.92), average distance of accelerations (p < .001; d = 0.83) and decelerations (p = .03; d = 1.30), and starting speed of accelerations (p = .01; d = 0.92) and decelerations (p = .04; d = 1.28). These results provide useful context when interpreting global positioning system–derived player-tracking metrics and can improve positional-specific training programs.
Target Discovery for Host-Directed Antiviral Therapies: Application of Proteomics Approaches
Authors: Cakir Merve , Obernier Kirsten , Forget Antoine , Krogan Nevan J.
Published: September 2021

Current epidemics, such as HIV or influenza, and the emergence of new threatening pathogens, such as the one causing the current coronavirus disease 2019 (COVID-19) pandemic, represent major global health challenges. While vaccination is an important part of the arsenal to counter the spread of viral diseases, it presents limitations and needs to be complemented by efficient therapeutic solutions.
The Future of Virology is Synthetic
Authors: White Richard Allen
Published: September 2021

The virosphere represents a vast library of unknown genes on the planet. Synthetic biology through engineering principles could be the key to unlocking this massive global gene repository.
Fifteen-minute consultation: Airway management in the acutely unwell child requiring intubation for the general paediatrician
Authors: Shires Peter , Harlow Georgina , Holecova Agata
Published: September 2021

Emergency endotracheal intubation is a high risk procedure in acutely unwell children and is commonly jointly managed by paediatricians and anaesthetists. This article aims to develop a shared understanding of the practicalities and language around the risk factors for difficult intubation and management of failed intubation, including the approach to situations where you cannot intubate and or cannot ventilate, to improve communication and team working between these dynamic interdisciplinary teams.
How to interpret the paediatric 12-lead ECG
Authors: Mikrou Paraskevi , Shivaram Pushpa , Kanaris Constantinos
Published: September 2021

ECG interpretation is a core skill for any healthcare practitioner that looks after children. The article aims to educate the reader in basic interpretation of paediatric ECG in a succinct, interactive, organised manner in a way that it can be easily referenced and applied in everyday clinical practice. We include clinical examples as well as age and sex-related reference ranges for QT intervals, P-wave duration, Q-wave amplitude, QRS complex duration, R-wave and S-wave amplitude, R/S ratio and PR intervals.
Cranial nerve palsies, SIADH and atrial fibrillation: a diagnostic challenge
Authors: Karna Rahul , Hans Bandhul , Murone Julie , Black John
Published: September 2021

We recently encountered a 79-year-old Caucasian man who presented with blurring of vision and facial muscle weakness. The patient also had hyponatraemia, atrial fibrillation with rapid ventricular response and underlying Brugada type II pattern. Urine and serum osmolality were consistent with syndrome of inappropriate antidiuretic hormone secretion (SIADH). It was only after extensive imaging and workup that we were able to tie together these three different presentations of Lyme disease—cranial nerve palsies, SIADH and atrial fibrillation and treat them accordingly. To the best of our knowledge, only eight cases of SIADH in patients with Lyme neuroborreliosis have been reported in the literature. Although our patient did not have a history of arrhythmias, case findings suggest that underlying Brugada type II morphology could have been the predisposing factor, and Lyme disease the trigger.
The quality of medical products for cardiovascular diseases: a gap in global cardiac care
Authors: Do Ngan Thi , Bellingham Konnie , Newton Paul N , Caillet Céline
Published: September 2021

Objective

Good quality cardiovascular medicines and devices are crucial in the prevention and management of the ever-growing threats of cardiovascular diseases (CVDs) globally. Yet our current understanding of the extent and impact of substandard and falsified (SF) cardiovascular medical products is poor. Our objective was to review the available literature on SF cardiovascular medicines/devices, with a focus on prevalence studies to discuss their impacts on public health.

Methods

Searches were conducted in Embase, PubMed, Web of Science, Google Scholar, Google and websites with interest in medicines/devices quality up to 31 August 2020. Articles in English and French identified in these searches were screened for eligibility. The Medicine Quality Assessment Reporting Guidelines was used to assess the quality of prevalence surveys, and we report according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.

Results

A total of 279 articles were included, which were subcategorised into prevalence surveys (n=28), equivalence studies (n=118), stability studies (n=5), routine quality control analyses (n=15), bioavailability studies (n=2), recalls/seizures/case reports (n=77), general discussions (n=24) and reviews (n=10). A failure frequency (defined as the proportion of samples that failed at least one quality test described in the report) of 525 (15.4%) was observed for the 3414 samples tested for quality in the 27 prevalence surveys with sufficient information for inclusion in our quantitative analysis. Nineteen surveys (70.4%) used convenience outlet sampling. The majority (88.8%, 3032/3414) of samples included in prevalence surveys were collected from low-income and middle-income countries. The most common defects were out-of-specification active ingredient(s) content, impurity/contaminant content and impaired dissolution. We found 26 incidents describing SF cardiovascular devices with 181 related deaths but no prevalence surveys.

Conclusion

The data suggest that SF cardiovascular products are likely to be a serious public health problem that has received limited attention. We do not suggest that 15.4% of cardiovascular medicines are SF, and our findings highlight the need for more research with robust methodology to provide more accurate prevalence estimates in order to inform policy and implement measures to ensure the quality of cardiovascular medicines and devices within the supply chain. Ensuring that CVD medical products are of good quality would help ensure effectiveness and that the benefits of therapy are realised in the prevention and treatment of CVDs.
Neonatal resuscitation practices in Uganda: a video observational study
Authors: Helldén Daniel , Myrnerts Höök Susanna , Pejovic Nicolas J , Mclellan Dan , Lubulwa Clare , Tylleskär Thorkild , Alfven Tobias
Published: September 2021

Background

Neonatal mortality, often due to birth asphyxia, remains stubbornly high in sub-Saharan Africa. Guidelines for neonatal resuscitation, where achieving adequate positive pressure ventilation (PPV) is key, have been implemented in low-resource settings. However, the actual clinical practices of neonatal resuscitation have rarely been examined in these settings. The primary aim of this prospective observational study was to detail the cumulative proportion of time with ventilation during the first minute on the resuscitation table of neonates needing PPV at the Mulago National Referral Hospital in Kampala, Uganda.

Methods

From November 2015 to January 2016, resuscitations of non-breathing neonates by birth attendants were video-recorded using motion sensor cameras. The resuscitation practices were analysed using the application NeoTapAS and compared between those taking place in the labour ward and those in theatre through Fisher’s exact test and Wilcoxon rank-sum test.

Results

From 141 recorded resuscitations, 99 were included for analysis. The time to initiation of PPV was 66 (42–102) s overall, and there was minimal PPV during the first minute in both groups with 0 (0–10) s and 0 (0–12) s of PPV, respectively. After initiating PPV the overall duration of interruptions during the first minute was 28 (18–37) s. Majority of interruptions were caused by stimulation (28%), unknown reasons (25%) and suction (22%).

Conclusions

Our findings show a low adherence to standard resuscitation practices in 2015–2016. This emphasises the need for continuous educational efforts and investments in staff and adequate resources to increase the quality of clinical neonatal resuscitation practices in low-resource settings.
Histone H3K27 demethylase KDM6A is an epigenetic gatekeeper of mTORC1 signalling in cancer
Authors: Revia Steffie , Seretny Agnieszka , Wendler Lena , Banito Ana , Eckert Christoph , Breuer Kersten , Mayakonda Anand , Lutsik Pavlo , Evert Matthias , Ribback Silvia , Gallage Suchira , Chikh Bakri Ismaiel , Breuhahn Kai , Schirmacher Peter , Heinrich Stefan , Gaida Matthias M , Heikenwälder Mathias , Calvisi Diego F , Plass Christoph , Lowe Scott W , Tschaharganeh Darjus F
Published: September 2021

Objective

Large-scale genome sequencing efforts of human tumours identified epigenetic modifiers as one of the most frequently mutated gene class in human cancer. However, how these mutations drive tumour development and tumour progression are largely unknown. Here, we investigated the function of the histone demethylase KDM6A in gastrointestinal cancers, such as liver cancer and pancreatic cancer.

Design

Genetic alterations as well as expression analyses of KDM6A were performed in patients with liver cancer. Genetic mouse models of liver and pancreatic cancer coupled with Kdm6a-deficiency were investigated, transcriptomic and epigenetic profiling was performed, and in vivo and in vitro drug treatments were conducted.

Results

KDM6A expression was lost in 30% of patients with liver cancer. Kdm6a deletion significantly accelerated tumour development in murine liver and pancreatic cancer models. Kdm6a-deficient tumours showed hyperactivation of mTORC1 signalling, whereas endogenous Kdm6a re-expression by inducible RNA-interference in established Kdm6a-deficient tumours diminished mTORC1 activity resulting in attenuated tumour progression. Genome-wide transcriptional and epigenetic profiling revealed direct binding of Kdm6a to crucial negative regulators of mTORC1, such as Deptor, and subsequent transcriptional activation by epigenetic remodelling. Moreover, in vitro and in vivo genetic epistasis experiments illustrated a crucial function of Deptor and mTORC1 in Kdm6a-dependent tumour suppression. Importantly, KDM6A expression in human tumours correlates with mTORC1 activity and KDM6A-deficient tumours exhibit increased sensitivity to mTORC1 inhibition.

Conclusion

KDM6A is an important tumour suppressor in gastrointestinal cancers and acts as an epigenetic toggle for mTORC1 signalling. Patients with KDM6A-deficient tumours could benefit of targeted therapy focusing on mTORC1 inhibition.
Association of carbohydrate and saturated fat intake with cardiovascular disease and mortality in Australian women
Authors: Gribbin Sarah , Enticott Joanne , Hodge Allison M , Moran Lisa , Thong Eleanor , Joham Anju , Zaman Sarah
Published: September 2021

Background

Conflicting evidence surrounds the effect of dietary macronutrient intake (fat, carbohydrate and protein) on cardiovascular disease (CVD), particularly in women.

Methods

Women (aged 50–55 years) were recruited into the Australian Longitudinal Study on Women’s Health. Women were divided into quintiles according to their carbohydrate and saturated fat intake as a percentage of total energy intake (TEI). The primary endpoint was new-onset CVD (heart disease/stroke). Secondary endpoints included all-cause mortality, incident hypertension, obesity and/or diabetes mellitus. Multivariate logistic regression models assessed for associations with the primary and secondary endpoints, with adjustment for confounders.

Results

A total of 9899 women (mean age 52.5±1.5 years) were followed for 15 years, with 1199 incident CVD and 470 deaths. On multivariable analysis, higher carbohydrate intake was associated with lower CVD risk (ptrend<0.01), with the lowest CVD risk for quintile 3 (41.0%–44.3% energy as carbohydrate) versus quintile 1 (<37.1% energy as carbohydrate) (OR 0.56, 95% CI 0.35 to 0.91, p=0.02). There was no significant association between carbohydrate intake and mortality (ptrend=0.69) or between saturated fat intake and CVD (ptrend=0.29) or mortality (ptrend=0.25). Both increasing saturated fat and carbohydrate intake were significantly inversely associated with hypertension, diabetes mellitus and obesity (ptrend<0.01 for all).

Conclusions

In middle-aged Australian women, moderate carbohydrate intake (41.0%–44.3% of TEI) was associated with the lowest risk of CVD, without an effect on total mortality. Increasing saturated fat intake was not associated with CVD or mortality and instead correlated with lower rates of diabetes, hypertension and obesity.
Hydration for prevention of kidney injury after primary coronary intervention for acute myocardial infarction: a randomised clinical trial
Authors: Liu Yong , Tan Ning , Huo Yong , Chen Shiqun , Liu Jin , Chen Yun-Dai , Wu Keng , Wu Guifu , Chen Kaihong , Ye Jianfeng , Liang Yan , Feng Xinwu , Dong Shaohong , Wu Qiming , Ye Xianhua , Zeng Hesong , Zhang Minzhou , Dai Min , Duan Chong-Yang , Sun Guoli , He Yibo , Song Feier , Guo Zhaodong , Chen Ping-Yan , Ge Junbo , Xian Ying , Chen Jiyan
Published: September 2021

Objective

To evaluate the efficacy of aggressive hydration compared with general hydration for contrast-induced acute kidney injury (CI-AKI) prevention among patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).

Methods

The Aggressive hydraTion in patients with STEMI undergoing pPCI to prevenT Contrast-Induced Acute Kidney Injury study is an open-label, randomised controlled study at 15 teaching hospitals in China. A total of 560 adult patients were randomly assigned (1:1) to receive aggressive hydration or general hydration treatment. Aggressive hydration group received preprocedural loading dose of 125/250 mL normal saline within 30 min, followed by postprocedural hydration performed for 4 hours under left ventricular end-diastolic pressure guidance and additional hydration until 24 hours after pPCI. General hydration group received ≤500 mL 0.9% saline at 1 mL/kg/hour for 6 hours after randomisation. The primary end point is CI-AKI, defined as a >25% or 0.5 mg/dL increased in serum creatinine from baseline during the first 48–72 hours after primary angioplasty. The safety end point is acute heart failure.

Results

From July 2014 to May 2018, 469 patients were enrolled in the final analysis. CI-AKI occurred less frequently in aggressive hydration group than in general hydration group (21.8% vs 31.1%; risk ratio (RR) 0.70, 95% CI 0.52 to 0.96). Acute heart failure did not significantly differ between the aggressive hydration group and the general hydration group (8.1% vs 6.4%, RR 1.13, 95% CI 0.66 to 2.44). Several subgroup analysis showed the better effect of aggressive hydration in CI-AKI prevention in male, renal insufficient and non-anterior myocardial infarction participants.

Conclusions

Comparing with general hydration, the peri-operative aggressive hydration seems to be safe and effective in preventing CI-AKI among patients with STEMI undergoing pPCI.
Predictors of short-term impulsive and compulsive behaviour after subthalamic stimulation in Parkinson disease
Authors: Sauerbier Anna , Loehrer Philipp , Jost Stefanie T. , Heil Shania , Petry-Schmelzer Jan N. , Herberg Johanna , Bachon Pia , Aloui Salima , Gronostay Alexandra , Klingelhoefer Lisa , Baldermann J. Carlos , Huys Daniel , Nimsky Christopher , Barbe Michael T. , Fink Gereon R. , Martinez-Martin Pablo , Ray Chaudhuri K. , Visser-Vandewalle Veerle , Timmermann Lars , Weintraub Daniel , Dafsari Haidar S.
Published: September 2021

Background

The effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson’s disease (PD) are understudied.

Objective

To investigate clinical predictors of STN-DBS effects on ICB.

Methods

In this prospective, open-label, multicentre study in patients with PD undergoing bilateral STN-DBS, we assessed patients preoperatively and at 6-month follow-up postoperatively. Clinical scales included the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), PD Questionnaire-8, Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale in addition to levodopa-equivalent daily dose total (LEDD-total) and dopamine agonists (LEDD-DA). Changes at follow-up were analysed with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We explored predictors of QUIP-RS changes using correlations and linear regressions. Finally, we dichotomised patients into ‘QUIP-RS improvement or worsening’ and analysed between-group differences.

Results

We included 55 patients aged 61.7 years±8.4 with 9.8 years±4.6 PD duration. QUIP-RS cut-offs and psychiatric assessments identified patients with preoperative ICB. In patients with ICB, QUIP-RS improved significantly. However, we observed considerable interindividual variability of clinically relevant QUIP-RS outcomes as 27.3% experienced worsening and 29.1% an improvement. In post hoc analyses, higher baseline QUIP-RS and lower baseline LEDD-DA were associated with greater QUIP-RS improvements. Additionally, the ‘QUIP-RS worsening’ group had more severe baseline impairment in the NMSS attention/memory domain.

Conclusions

Our results show favourable ICB outcomes in patients with higher preoperative ICB severity and lower preoperative DA doses, and worse outcomes in patients with more severe baseline attention/memory deficits. These findings emphasise the need for comprehensive non-motor and motor symptoms assessments in patients undergoing STN-DBS.

Trial registration number

DRKS00006735.
Withering Minds: towards a unified embodied mind theory of personal identity for understanding dementia
Authors: Lyreskog David M
Published: September 2021

A prominent view on personal identity over time, Jeff McMahan’s ‘Embodied Mind Account’ (2002) holds that we cease to exist only once our brains can no longer sustain the basic capacity to uphold consciousness. One of the many implications of this view on identity persistence is that we continue to exist throughout even the most severe cases of dementia, until our consciousness irreversibly shuts down. In this paper, I argue that, while the most convincing of prominent accounts of personal identity over time, McMahan’s account faces serious challenges in explanatory power of dementias and related neurodegenerative conditions. Particularly, this becomes visible in the face of emerging methods for neural tissue regeneration, and the possibility of ‘re-emerging patients’. I argue that medical professionals’ neglecting qualitative aspects of identity risks resulting in grave misunderstandings in decision-making processes, and ethically objectionable outcomes in future practices. Finally, I propose revisions which could potentially salvage the great benefits that Embodied Mind Theory still can bring to the field of dementia care in terms of understanding life, death, and identity across the lifespan.
Compulsory treatment of physical illness under MHA 1983
Authors: Wheeler Robert , Ruck Keene Alexander
Published: September 2021

Taken together, Sections 145 and 63 of the Mental Health Act 1983 (MHA) provide for treatment without consent of physical illness ancillary to the mental disorder with which a patient presents. On a daily basis, clinicians make both the decision that the Act’s authority can be applied to their patient’s case, and that it should be applied. But in the unusual circumstances where there is uncertainty as to the applicability of the MHA to the ancillary treatment of physical illness, the assistance of a court may be sought. In so doing, the law (and thence the courts) may justify compulsion but never prescribes it; the clinician is presented with authority that he or she could use but is left to decide whether it should be employed. This paper explores how the clinical question is set before the court, and whether the distinction between symptom, manifestation and consequence is sufficiently understood. This has important consequences in the context of self-neglect and its close cousin self-harm: the question whether the relevant ailment was attributable to or exacerbated by neglect or self- inflicted harm will determine whether compulsion under the MHA is applicable; and furthermore, whether or not compulsion is clinically acceptable.
Opt-out paradigms for deceased organ donation are ethically incoherent
Authors: Qurashi G M
Published: September 2021

The Organ Donation Act 2019 has introduced an opt-out organ donor register in England, meaning that consent to the donation of organs upon death is presumed unless an objection during life was actively expressed. By assessing the rights of the dead over their organs, the sick to those same organs, and the role of consent in their requisition, this paper interrogates whether such paradigms for deceased organ donation are ethically justifiable. Where legal considerations are applicable, I focus on the recent changes in England as a case in point; however, this paper ultimately challenges the justifiability of opt-out systems in any form, concluding that ethical solutions to organ shortage do not lie in opt-out systems of deceased organ procurement.
Guilt, shame and negative emotion in undergraduate medical education: is there a role for Balint groups?
Authors: Greenlees George , Archer Laura
Published: September 2021

Balint groups are a structured discussion which explores non-clinical aspects of the doctor–patient relationship. In this commentary piece we describe our experience of a Balint group for final-year medical students in a large regional hospital. We discuss that our participants reported a significant burden of negative emotion, primarily guilt and shame, in attempting to navigate the hospital environment as learners. We note how our participants perceived they would acquire the ability to manage these negative emotions simply by becoming doctors, despite being only a few months from qualification. A cultural shift in undergraduate training, combined with a challenging period for the medical profession in general, may leave new doctors isolated in the face of the emotional strain of medicine. We therefore encourage educators to consider using Balint groups as an adjunct to more traditional clinical training.
Faecal microbiota transplants: towards a healthy disgust scepticism
Authors: Houf Jessica
Published: September 2021

This paper engages with the obstacle of disgust surrounding the use of faecal microbiota transplants (FMT). In discourse about the human microbiome and microbiota-based therapies (like FMT), disgust has become an unavoidable emotion for physicians, patients and caregivers interested in these therapies. Additionally, microbiota therapies and microbiomes are challenging our conception of an individual biological self. As these two discourses converge with FMT, it becomes necessary to understand how they are working together. To do this, this paper explores the way disgust functions in the formation of subjects. Scholarship about disgust can be categorised into two approaches: disgust as a deep wisdom or disgust scepticism. The former approach focuses on the physiological, embodied aspects of our disgust reactions as evidence of ‘truth’ in disgusting encounters, and the latter recognises the way disgust is culturally contingent and adapted for use in moral and social determinations of good and bad. However, both positions accept the use of disgust as a defence against ‘toxins and diseases’. Yet, as this paper argues, we should take the sceptical approach further. The disgust sceptical approach, particularly as developed by Sarah Ahmed, does more than just challenge disgust’s role in moral deliberations. It also demands sceptical reflection on disgust as a universal defence against ‘toxins and diseases’. Much as disgust can be co-opted to support oppression, it too can be co-opted to reconstitute a false vision of human subjectivity—the coherent, contained and exceptional human subject situated above the natural world. The human microbiome, faecal therapeutics and being disgusted give us an opportunity to recognise ourselves as more-than-human subjects.
‘Working in a comfort formerly unknown’: medical holism and the radical ambitions behind interwar Bermondsey’s foot clinic
Authors: Mitchell Christopher T
Published: September 2021

In 1930, the Bermondsey Public Health Department made the rather unusual decision to establish the first municipal foot clinic in Britain. This pioneering and popular clinic was founded at a time when the aims of public health were being renegotiated. Historical discussion of the reconceptualisation of public health in the interwar period typically depicts a paradigm shift in which public health was no longer focused solely on sanitising the physical environment, but was characterised by an additional, separate aim: the development of hygienic behaviour within patients. While this narrative has proved helpful in explaining the emergence of health education between the wars, Bermondsey’s foot clinic challenges it somewhat. In essence, the foot clinic was an inventive and multifaceted attempt to treat Bermondsey’s rampant poverty. Chiefly, the clinic sought to improve the occupational fitness of the population in an area where most jobs required workers to be stood up all day. In addition, the foot clinic was expected to provoke physiological and spiritual renewal by freeing patients to move more naturally, according to specific contemporary modernist theories of movement. Finally, the architecture of the building which housed the foot clinic was designed to encourage its patients to adopt more hygienic ways of living in their own homes. Thus, the clinic’s aims are difficult to compartmentalise into either sanitisation of the lived environment or health education, since it sought to achieve both goals simultaneously. Fundamentally, this integrated approach to public health was rooted in a concept of health that upheld the interconnectedness of individual, communal and environmental well-being.
Temporal association of prostate cancer incidence with World Trade Center rescue/recovery work
Authors: Goldfarb David G , Zeig-Owens Rachel , Kristjansson Dana , Li Jiehui , Brackbill Robert M , Farfel Mark R , Cone James E , Yung Janette , Kahn Amy R , Qiao Baozhen , Schymura Maria J , Webber Mayris P , Dasaro Christopher R , Shapiro Moshe , Todd Andrew C , Prezant David J , Boffetta Paolo , Hall Charles B
Published: September 2021

Background

The World Trade Center (WTC) attacks on 11 September 2001 created a hazardous environment with known and suspected carcinogens. Previous studies have identified an increased risk of prostate cancer in responder cohorts compared with the general male population.

Objectives

To estimate the length of time to prostate cancer among WTC rescue/recovery workers by determining specific time periods during which the risk was significantly elevated.

Methods

Person-time accruals began 6 months after enrolment into a WTC cohort and ended at death or 12/31/2015. Cancer data were obtained through linkages with 13 state cancer registries. New York State was the comparison population. We used Poisson regression to estimate hazard ratios and 95% CIs; change points in rate ratios were estimated using profile likelihood.

Results

The analytic cohort included 54 394 male rescue/recovery workers. We observed 1120 incident prostate cancer cases. During 2002–2006, no association with WTC exposure was detected. Beginning in 2007, a 24% increased risk (HR: 1.24, 95% CI 1.16 to 1.32) was observed among WTC rescue/recovery workers when compared with New York State. Comparing those who arrived earliest at the disaster site on the morning of 11 September 2001 or any time on 12 September 2001 to those who first arrived later, we observed a positive, monotonic, dose-response association in the early (2002–2006) and late (2007–2015) periods.

Conclusions

Risk of prostate cancer was significantly elevated beginning in 2007 in the WTC combined rescue/recovery cohort. While unique exposures at the disaster site might have contributed to the observed effect, screening practices including routine prostate specific antigen screening cannot be discounted.
COVID-19 infection among bartenders and waiters before and after pub lockdown
Authors: Methi Fredrik , Telle Kjetil , Magnusson Karin
Published: September 2021

Objective

To assess how different bans on serving alcohol in Norwegian bars and restaurants were related to the detection of SARS-CoV-2 in bartenders and waiters and in persons in any occupation.

Methods

In 25 392 bartenders and waiters and 1 496 328 persons with other occupations (mean (SD) age 42.0 (12.9) years and 51.8% men), we examined the weekly rates of workers tested and detected with SARS-CoV-2, 1–10 weeks before and 1–5 weeks after implementation of different degrees of bans on serving alcohol in pubs and restaurants, across 102 Norwegian municipalities with: (1) full blanket ban, (2) partial ban with hourly restrictions (eg, from 22:00 hours) or (3) no ban, adjusted for age, sex, testing behaviour and population size.

Results

By 4 weeks after the implementation of ban, COVID-19 infection among bartenders and waiters had been reduced by 60% (from 2.8 (95% CI 2.0 to 3.6) to 1.1 (95% CI 0.5 to 1.6) per 1000) in municipalities introducing full ban, and by almost 50% (from 2.5 (95% CI 1.5 to 3.5) to 1.3 (95% CI 0.4 to 2.2) per 1000) in municipalities introducing partial ban. A similar reduction within 4 weeks was also observed for workers in all occupations, both in municipalities with full (from 1.3 (95% CI 1.3 to 1.4) to 0.9 (95% CI 0.9 to 1.0)) and partial bans (from 1.2 (95% CI 1.1 to 1.3) to 0.5 (95% CI 0.5 to 0.6)).

Conclusion

Partial bans on serving alcohol in bars and restaurants may be similarly associated with declines in confirmed COVID-19 infection as full bans.
Paraneoplastic neurological syndromes: a practical approach to diagnosis and management
Authors: Binks Sophie , Uy Christopher , Honnorat Jerome , Irani Sarosh R
Published: September 2021

Paraneoplastic neurological syndromes (PNS) are the immune-mediated effects of a remote cancer and are characterised by an autoantibody response against antigens expressed by the tumour. Classically, well-characterised ‘onconeuronal’ antibodies target intracellular antigens and hence cannot access their antigens across intact cell membranes. The pathogenic mediators are likely to be neuronal-specific T cells. There is a variable response to immunotherapies and the clinical syndrome helps to direct the search for a specific set of tumours. By contrast, many newly emerging autoantibodies with oncological associations target cell surface epitopes and can exert direct pathogenic effects on both the central and peripheral nervous systems. Patients with these cell-surface directed autoantibodies often clearly respond to immunotherapies. Overall, the clinical, serological and oncological features in an individual patient help to determine the clinical relevance of the syndrome and hence guide its management. We summarise current knowledge and a practical approach to the investigation, diagnosis, treatment and outcomes of patients with suspected PNS.
No widespread dissemination of Chlamydia trachomatis diagnostic-escape variants and the impact of Neisseria gonorrhoeae positivity on the Aptima Combo 2 assay
Authors: Cole Michelle Jayne , Davis Grahame S , Fifer Helen , Saunders John Michael , Unemo Magnus , Hadad Ronza , Roberts David J , Fazal Mohammed , Day Michaela Joanne , Minshull Jack , Muir Peter , Horner Paddy J , Gill Noel O , Folkard Kate
Published: September 2021

Objectives

A Finnish Chlamydia trachomatis (CT) new variant was detected in 2019 that escaped detection in the Hologic Aptima Combo 2 (AC2) assay due to a C1515T mutation in the CT 23S rRNA target region. Reflex testing of CT-negative/CT-equivocal specimens as well as those positive for Neisseria gonorrhoeae (NG) with the Hologic Aptima CT (ACT) assay was recommended to identify any CT variants.

Methods

From June to October 2019, specimens with discrepant AC2/ACT CT results were submitted to Public Health England and screened for detectable CT DNA using an inhouse real-time (RT)-PCR. When enough DNA was present, partial CT 23S rRNA gene sequencing was performed. Analysis of available relative light units and interpretative data was performed.

Results

A total of 317 discordant AC2/ACT specimens were collected from 315 patients. Three hundred were tested on the RT-PCR; 53.3% (n=160) were negative and 46.7% (n=140) were positive. Due to low DNA load in most specimens, sequencing was successful for only 36 specimens. The CT 23S rRNA wild-type sequence was present in 32 specimens, and two variants with C1514T or G1523A mutation were detected in four specimens from three patients. Of the discordant specimens with NG interpretation, 36.6% of NG-negative/CT-negative AC2 specimens had detectable CT DNA on the inhouse RT-PCR vs 53.3% of NG-positive/CT-negative specimens.

Conclusions

No widespread dissemination of AC2 diagnostic-escape CT variants has occurred in England. We however identified the impact of NG positivity on the discordant AC2/ACT specimens; a proportion appeared due to NG positivity and the associated NG signal, rather than any diagnostic-escape variants or low DNA load. Several patients with gonorrhoea may therefore receive false-negative AC2 CT results. Single diagnostic targets and multiplex diagnostic assays have their limitations such as providing selection pressure for escape mutants and potentially reduced sensitivity, respectively. These limitations must be considered when establishing diagnostic pathways.
Social mobility and gonorrhoea in Germany during 2020
Authors: Sulyok Mihály , Walker Mark
Published: September 2021

Objectives

The incidence of STIs is likely to be related to levels of social activity and mobility. Novel datasets detailing levels of social activity were made widely available during the COVID-19 pandemic. These allow the relationship between activity and STI incidence to be examined.

Methods

The correlation between social activities and the reported number of gonorrhoea cases between March and December 2020 in Germany was studied. Regression through Autoregressive Integrated Moving Average (ARIMA) time series modelling identified those activities associated with case numbers.

Results

ARIMA regression identified a significant association with ‘transit’ activity within the Apple data and ‘parks’ within Google.

Conclusions

This study illustrates the potential newly available measures of social activity provided for STI research. Reductions in STI incidence are likely to have occurred due to COVID-19 social restrictions. Although other studies report reductions in infectious diseases during this period, few examine the potential social factors mediating this. The results illustrate the continual need for sexual health services throughout the pandemic.
Endoplasmic reticulum-unfolded protein response signalling is altered in severe eosinophilic and neutrophilic asthma
Authors: Pathinayake Prabuddha S , Waters David W , Nichol Kristy S , Brown Alexandra C , Reid Andrew T , Hsu Alan Chen-Yu , Horvat Jay C , Wood Lisa G , Baines Katherine J , Simpson Jodie L , Gibson Peter G , Hansbro Philip M , Wark Peter A B
Published: September 2021

Introduction

The significance of endoplasmic reticulum (ER) stress in asthma is unclear. Here, we demonstrate that ER stress and the unfolded protein response (UPR) are related to disease severity and inflammatory phenotype.

Methods

Induced sputum (n=47), bronchial lavage (n=23) and endobronchial biopsies (n=40) were collected from participants with asthma with varying disease severity, inflammatory phenotypes and from healthy controls. Markers for ER stress and UPR were assessed. These markers were also assessed in established eosinophilic and neutrophilic murine models of asthma.

Results

Our results demonstrate increased ER stress and UPR pathways in asthma and these are related to clinical severity and inflammatory phenotypes. Genes associated with ER protein chaperone (BiP, CANX, CALR), ER-associated protein degradation (EDEM1, DERL1)and ER stress-induced apoptosis (DDIT3, PPP1R15A) were dysregulated in participants with asthma and are associated with impaired lung function (forced expiratory volume in 1 s) and active eosinophilic and neutrophilic inflammation. ER stress genes also displayed a significant correlation with classic Th2 (interleukin-4, IL-4/13) genes, Th17 (IL-17F/CXCL1) genes, proinflammatory (IL-1b, tumour necrosis factor α, IL-8) genes and inflammasome activation (NLRP3) in sputum from asthmatic participants. Mice with allergic airway disease (AAD) and severe steroid insensitive AAD also showed increased ER stress signalling in their lungs.

Conclusion

Heightened ER stress is associated with severe eosinophilic and neutrophilic inflammation in asthma and may play a crucial role in the pathogenesis of asthma.
Connecting plant species and natural products from the Canadian prairie ecological zone to biomedical knowledge
Authors: Molina Layla , Allard Haley K. , Kernéis Sophie M. , Golsteyn Roy M.
Published: September 2021

Natural products from plants in Canadian ecological zones are understudied. There are, however, sound scientific arguments to justify investigation of natural products from plant species found within these zones. Here, we review a broad range of scientific and local literature describing the features of the Canadian prairie ecological zone and the Asteraceae taxonomical family. Species from Asteraceae are well represented in the prairie ecological system, although very few have been investigated for natural products with biomedical properties. Data from a range of sources that address ecological interactions, abiotic features, and Traditional Knowledge provide a foundation for future scientific studies of plant natural products found within Canadian borders. We draw from discoveries of the Asteraceae family and one of its major classes of secondary metabolites, sesquiterpenes, to stimulate research of Asteraceae species in Canada.
High temperatures disturb ovule development in field pea (Pisum sativum)
Authors: Osorio Evelyn E. , Davis Arthur R. , Bueckert Rosalind A.
Published: September 2021

High temperatures affect reproductive growth and lead to yield loss in many crops. Field pea is heat sensitive, but little is known about the effect of high temperatures on field pea ovules. We investigated the impact of heat on ovules of flowers at various reproductive nodes of field pea using growth chambers. We exposed 6 cultivars exhibiting diverse heat tolerance to 4 days of heat (35 °C day/18 °C night) during early flowering. Post-treatment ovules and embryo sacs were assessed using clearing by light microscopy and fluorescence microscopy. Results indicated that greater ovule and embryo sac development occurred on some nodes, but poor ovule and embryo sac expansion resulted on other nodes of the same heat-treated plants. Whereas advanced ovule and embryo sac development were identified on heat-tolerant cultivars, a combination of advanced and less advanced ovule and embryo sac development occurred in intermediate and heat-sensitive cultivars. More than 90% of the affected ovules displayed embryos at various stages of development, which indicated disruption around fertilization or shortly thereafter. Callose accumulation around the vascular bundle within ovules suggested disruption of assimilate transport to the embryo sac. The contrasting pattern of ovule development at different nodes implied a conflict between early aging and maternal supply of heat-treated plants.
Myxobolus cerebralisestablishment and spread: a graphical synthesis
Authors: Ramazi Pouria , Fischer Samuel M. , Alexander Julie , James Clayton T. , Paul Andrew J. , Greiner Russell , Lewis Mark A.
Published: September 2021

Myxobolus cerebralis is the parasite causing whirling disease, which has dramatic ecological impacts due to its potential to cause high mortality in salmonids. The large-scale efforts, necessary to underpin an effective surveillance program, have practical and economic constraints. There is, hence, a clear need for models that can predict the parasite spread. Model development, however, often heavily depends on knowing influential variables and governing mechanisms. We have developed a graphical model for the establishment and spread of M. cerebralis by synthesizing experts’ opinion and empirical studies. First, we conducted a series of workshops with experts to identify variables believed to impact the establishment and spread of the parasite M. cerebralis and visualized their interactions via a directed acyclic graph. Then we refined the graph by incorporating empirical findings from the literature. The final graph’s nodes correspond to variables whose considerable impact on M. cerebralis establishment and spread is either supported by empirical data or confirmed by experts, and the graph’s directed edges represent direct causality or strong correlation. This graphical model facilitates communication and education of whirling disease and provides an empirically driven framework for constructing future models, especially Bayesian networks.
Long-term interplay between harvest regimes and biophysical conditions may lead to persistent changes in age at sexual maturity of Northeast Arctic cod (Gadus morhua)
Authors: Rørvik Carl Jakob , Bogstad Bjarte , Ottersen Geir , Kjesbu Olav Sigurd
Published: September 2021

This investigation commenced by constructing principal maturation schedule equations as a function of fishing mortality (F), key biophysical factors and a term attributed to fisheries-induced adaptive change (FIAC). Following the onset of industrial trawl fishery on the model stock, Northeast Arctic cod (NEAC; Gadus morhua) (1934–2020), F on immature age group 5–8 years (F5-8) increased and mean age at 50% maturity (A50) decreased from ≈10 years in the late 1940s to ≈7 years today. Large annual fluctuations in total stock biomass (TSB), sea temperature (KolaT) and F5-8 were used to better understand A50 responses. In the model, the annual accumulation of F5-8 drives FIAC. The model includes the option that NEAC may sustain F5-8 up to a certain level (F_bal) before FIAC becomes statistically evident, with F_bal falling between 0.00 and 0.40 for A50. This dynamic range in F_bal indicates a sophisticated, underlying adaptive response. Independent of F_bal, our analysis clarifies that FIAC is necessary to explain the observed changes in A50.
Configurable Analog Block Using Current-Mode Approach
Authors: Maheshwari Sudhanshu
Published: September 2021

This paper introduces a new current-mode approach based configurable analog block (CAB) operating in voltage-mode with high input resistance, employing only three impedances in grounded form and providing a wide range functionality. The fourteen functions realized by the CAB include amplifiers, integrators, differentiators, and filters. The nonideal and parasitic analysis of the proposed configurable block is carried out, along with detailed simulation studies using 0.25[Formula: see text][Formula: see text]m CMOS parameters and a supply of [Formula: see text]0.75[Formula: see text]V for justifying the advance to the field. The active element used for designing the CAB exhibits 1.9 and 0.8[Formula: see text]GHz as voltage and current transfer bandwidths, respectively, while also providing low output resistance of 105[Formula: see text][Formula: see text] in voltage conveying action. Thus, the proposed CAB benefits from high frequency performance and lesser sensitivity to errors due to parasitic at that terminal. Most of the functions utilize beneficial form of grounded components. Presentation of conclusive results for integrator, all-pass filter and band-pass filter is included in form of frequency and transient responses. In-depth intermodulation distortion results for band-pass filter are further given. General conclusive annotations on analog circuit design are made at the end of this study.