bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting the nociceptive somatosensory system with AAV9 and AAV2retro viral vectors
Authors: Skorput Alexander G.J. , Gore Reshma , Schorn Rachel , Riedl Maureen S. , de Velasco Ezequiel Marron Fernandez , Hadlich Bailey , Kitto Kelley F. , Fairbanks Carolyn A. , Vulchanova Lucy
Published: May 2021

Adeno-associated viral (AAV) vectors allow for site-specific and time-dependent genetic manipulation of neurons. However, for successful implementation of AAV vectors, major consideration must be given to the selection of viral serotype and route of delivery for efficient gene transfer into the cell type being investigated. Here we compare the transduction pattern of neurons in the somatosensory system following injection of AAV9 or AAV2retro in the parabrachial complex of the midbrain, the spinal cord dorsal horn, the intrathecal space, and the colon. Transduction was evaluated based on Cre-dependent expression of tdTomato in transgenic reporter mice, following delivery of AAV9 or AAV2retro carrying identical constructs that drive the expression of Cre/GFP. The pattern of distribution of tdTomato expression indicated notable differences in the access of the two AAV serotypes to primary afferent neurons via peripheral delivery in the colon and to spinal projections neurons via intracranial delivery within the parabrachial complex. Additionally, our results highlight the superior sensitivity of detection of neuronal transduction based on reporter expression relative to expression of viral products.
ATP disrupts lipid binding equilibrium to drive retrograde transport critical for bacterial outer membrane asymmetry
Authors: Low Wen-Yi , Thong Shuhua , Chng Shu-Sin
Published: May 2021

The hallmark of the Gram-negative bacterial envelope is the presence of the outer membrane (OM). The OM is asymmetric, comprising lipopolysaccharides (LPS) in the outer leaflet and phospholipids (PLs) in the inner leaflet; this critical feature confers permeability barrier function against external insults, including antibiotics. To maintain OM lipid asymmetry, the OmpC-Mla system is believed to remove aberrantly localized PLs from the OM and transport them to the inner membrane (IM). Key to the system in driving lipid trafficking is the MlaFEDB ABC transporter complex in the IM, but mechanistic details, including transport directionality, remain enigmatic. Here, we develop a sensitive point-to-point in vitro lipid transfer assay that allows direct tracking of [14C]-labelled PLs between the periplasmic chaperone MlaC and MlaFEDB reconstituted into nanodiscs. We reveal that MlaC spontaneously transfers PLs to the IM transporter in an MlaD-dependent manner that can be further enhanced by coupled ATP hydrolysis. In addition, we show that MlaD is important for modulating productive coupling between ATP hydrolysis and such retrograde PL transfer. We further demonstrate that spontaneous PL transfer also occurs from MlaFEDB to MlaC, but such anterograde movement is instead abolished by ATP hydrolysis. Our work uncovers a model where PLs reversibly partition between two lipid binding sites in MlaC and MlaFEDB, and ATP binding and/or hydrolysis shift this equilibrium to ultimately drive retrograde PL transport by the OmpC-Mla system. These mechanistic insights will inform future efforts towards discovering new antibiotics against Gram-negative pathogens.

Significance Statement

Biological membranes define cellular boundaries, allow compartmentalization, and represent a prerequisite for life. In Gram-negative bacteria, the outer membrane (OM) prevents entry of toxic substances, conferring intrinsic resistance against many antibiotics. This barrier function requires unequal distribution of lipids across the OM bilayer, yet how such lipid asymmetry is maintained is not well understood. In this study, we established the directionality of lipid transport for a conserved membrane protein complex, and uncovered mechanistic insights into how ATP powers such transport from the OM to the inner membrane. Our work provides fundamental understanding of lipid trafficking within the Gram-negative double-membrane envelope in the context of OM lipid asymmetry, and highlights the importance of targeting lipid transport processes for future antibiotics development.
A joint deep learning model enables simultaneous batch effect correction, denoising, and clustering in single-cell transcriptomics
Authors: Lakkis Justin , Wang David , Zhang Yuanchao , Hu Gang , Wang Kui , Pan Huize , Ungar Lyle , Reilly Muredach P. , Li Xiangjie , Li Mingyao
Published: May 2021

Recent developments of single-cell RNA-seq (scRNA-seq) technologies have led to enormous biological discoveries. As the scale of scRNA-seq studies increases, a major challenge in analysis is batch effects, which are inevitable in studies involving human tissues. Most existing methods remove batch effects in a low-dimensional embedding space. Although useful for clustering, batch effects are still present in the gene expression space, leaving downstream gene-level analysis susceptible to batch effects. Recent studies have shown that batch effect correction in the gene expression space is much harder than in the embedding space. Methods such as Seurat 3.0 rely on the mutual nearest neighbor (MNN) approach to remove batch effects in gene expression, but MNN can only analyze two batches at a time, and it becomes computationally infeasible when the number of batches is large. Here, we present CarDEC, a joint deep learning model that simultaneously clusters and denoises scRNA-seq data while correcting batch effects both in the embedding and the gene expression space. Comprehensive evaluations spanning different species and tissues showed that CarDEC outperforms Scanorama, DCA + Combat, scVI, and MNN. With CarDEC denoising, non-highly variable genes offer as much signal for clustering as the highly variable genes (HVGs), suggesting that CarDEC substantially boosted information content in scRNA-seq. We also showed that trajectory analysis using CarDEC's denoised and batch-corrected expression as input revealed marker genes and transcription factors that are otherwise obscured in the presence of batch effects. CarDEC is computationally fast, making it a desirable tool for large-scale scRNA-seq studies.
Characterizing dislocation loops in irradiated polycrystalline Zr alloys by X-ray line profile analysis of powder diffraction patterns with satellites
Authors: Ungár Tamás , Ribárik Gábor , Topping Matthew , Jones Rebecca M. A. , Dan Xu Xiao , Hulse Rory , Harte Allan , Tichy Géza , Race Christopher P. , Frankel Philipp , Preuss Michael
Published: May 2021

This work extends the convolutional multiple whole profile (CMWP) line profile analysis (LPA) procedure to determine the total dislocation density and character of irradiation-induced dislocation loops in commercial polycrystalline Zr specimens. Zr alloys are widely used in the nuclear industry as fuel cladding materials in which irradiation-induced point defects evolve into dislocation loops. LPA has long been established as a powerful tool to determine the density and nature of lattice defects in plastically deformed materials. The CMWP LPA procedure is based on the Krivoglaz–Wilkens theory in which the dislocation structure is characterized by the total dislocation density ρ and the dislocation arrangement parameter M. In commercial Zr alloys irradiation-induced dislocation loops broaden the peak profiles, mainly in the tail regions, and occasionally generate small satellites next to the Bragg peaks. In this work, two challenges in powder diffraction patterns of irradiated Zr alloys are solved: (i) determination of the M values from the long tail regions of peaks has been made unequivocal and (ii) satellites have been fitted separately, using physically well established principles, in order to exclude them from the dislocation determination process. Referring to the theory of heterogeneous dislocation distributions, determination of the total dislocation density from the main peaks free of satellites has been justified. The dislocation loop structure has been characterized by the total dislocation density of loops and the M parameter correlated to the dipole character of dislocation loops. The extended CMWP procedure is applied to determine the total dislocation density, the dipole character of dislocation loops, and the fractions of 〈a〉- and 〈c〉-type loops in proton- or neutron-irradiated polycrystalline Zr alloys used in the nuclear energy industry.
Unemployment and labor force participation in Italy
Authors: Nemore Francesco , Caferra Rocco , Morone Andrea
Published: May 2021

Purpose

Our main purpose is to test the unemployment invariance hypothesis in Italy.

Design/methodology/approach

This paper provides an empirical investigation of the unemployment and labor force participation in Italy.

Findings

Cointegration analysis results strongly suggest a clear long-run relationship between unemployment and labor force participation revealing a persistent and general added worker effect.

Originality/value

Our results seem to confute the unemployment invariance hypothesis.
Annual report narrative disclosures, information asymmetry and future firm performance: evidence from Vietnam
Authors: Tran Ly Thi Hai , Tu Thoa Thi Kim , Nguyen Tran Thi Hong , Nguyen Hoa Thi Lien , Vo Xuan Vinh
Published: May 2021

Purpose

This paper examines the role of the annual report’s linguistic tone in predicting future firm performance in an emerging market, Vietnam.

Design/methodology/approach

Both manual coding approach and the naïve Bayesian algorithm are employed to determine the annual report tone, which is then used to investigate its impact on future firm performance.

Findings

The study finds that tone can predict firm performance one year ahead. The predictability of tone is strengthened for firms that have a high degree of information asymmetry. Besides, the government’s regulatory reforms on corporate disclosures enhance the predictive ability of tone.

Research limitations/implications

The study suggests the naïve Bayesian algorithm as a cost-efficient alternative for human coding in textual analysis. Also, information asymmetry and regulation changes should be modeled in future research on narrative disclosures.

Practical implications

The study sends messages to both investors and policymakers in emerging markets. Investors should pay more attention to the tone of annual reports for improving the accuracy of future firm performance prediction. Policymakers should regularly revise and update regulations on qualitative disclosure to reduce information asymmetry.

Originality/value

This study enhances understanding of the annual report’s role in a non-Western country that has been under-investigated. The research also provides original evidence of the link between annual report tone and future firm performance under different information asymmetry degrees. Furthermore, this study justifies the effectiveness of the governments’ regulatory reforms on corporate disclosure in developing countries. Finally, by applying both the human coding and machine learning approach, this research contributes to the literature on textual analysis methodology.
Stock market co-movement in Latin America and the US: evidence from a new approach
Authors: Vatsa Puneet , Basnet Hem , Mixon Frank
Published: May 2021

Purpose

The purpose of this paper is to investigate the interlinkages among four major stock markets in Latin America, i.e., those in Argentina, Brazil, Chile, and Mexico, as well as their associations with the US stock market, which influences financial markets globally.

Design/methodology/approach

Using the newly developed Hamilton filter methodology (Hamilton, 2018), the authors decompose each stock series to extract cyclical components.

Findings

Results indicate that the US S&P 500 is weakly contemporaneously correlated with stock market indices in Brazil, Mexico and Argentina, whereas it also leads the latter by three months. As such, sufficient time is available for policymakers and investors to enhance their forecasts of the latter.

Originality/value

Results indicate that the US S&P 500 is weakly contemporaneously correlated with stock market indices in Brazil, Mexico and Argentina, whereas it also leads the latter by three months. As such, sufficient time is available for policymakers and investors to enhance their forecasts of the latter.
Access to surgical care as an efficiency issue: using lean management in French and Australian operating theatres
Authors: Mahmoud Zeyad , Angelé-Halgand Nathalie , Churruca Kate , Ellis Louise A , Braithwaite Jeffrey
Published: May 2021

Purpose

Millions around the world still cannot access safe, timely and affordable surgery. Considering access as a function of efficiency, this paper examines how the latter can be improved within the context of operating theatres. Carried out in France and Australia, this study reveals different types of waste in operating theatres and a series of successful tactics used to increase efficiency and eliminate wastefulness.

Design/methodology/approach

Data for this qualitative study were collected through 48 semi-structured interviews with operating theatre staff in France (n = 20) and Australia (n = 28). Transcripts were coded using a theory-driven thematic analysis to characterise sources of waste in operating theatres and the tactics used to address them.

Findings

The study confirmed the prominence of seven types of waste in operating theatres commonly found in industry and originally identified by Ohno, the initiator of lean: (1) underutilised operating rooms; (2) premature or delayed arrival of patients, staff or equipment; (3) need for large onsite storage areas and inventory costs; (4) unnecessary transportation of equipment; (5) needless staff movements; (6) over-processing and (7) quality defects. The tactics used to address each of these types of waste included multiskilling staff, levelling production and implementing just-in-time principles.

Originality/value

The tactics identified in this study have the potential of addressing the chronic and structurally embedded problem of waste plaguing health systems' operating theatres, and thus potentially improve access to surgical care. In a global context of resource scarcity, it is increasingly necessary for hospitals to optimise the ways in which surgery is delivered.
Modelling short‐term energetic costs of sonar disturbance to cetaceans using high‐resolution foraging data
Authors: Czapanskiy Max F. , Savoca Matthew S. , Gough William T. , Segre Paolo S. , Wisniewska Danuta M. , Cade David E. , Goldbogen Jeremy A.
Published: May 2021

Anthropogenic noise is a pervasive and increasing source of disturbance to wildlife. Marine mammals exhibit behavioural and physiological responses to naval sonar and other sound sources. The lost foraging opportunities and elevated locomotor effort associated with sonar disturbance likely carry energetic costs, which may lead to population‐level consequences.

We modelled the energetic costs associated with behavioural responses using (a) empirical datasets of cetacean feeding rates and prey characteristics and (b) allometry of swimming performance and metabolic rates.

We applied our model to compare the short‐term (i.e. the scale of the disturbance response; hours to days) energetic costs of a variety of observed behavioural responses. Efficient foragers (e.g. baleen whales) incur a greater relative energetic cost for mild behavioural responses as compared to the most extreme observed response for larger odontocetes (e.g. beaked whales). Energetic costs are more sensitive to lost feeding opportunities than increased energy expenditure from elevated locomotor effort.

To scale up from short‐term costs to long‐term effects (months to years), future research should address individuals’ capacity to compensate for energetic losses as well as energetic thresholds for demographic rates (survival, fecundity). We discuss how relative energetic costs correlate with species’ pace of life and the implications for conservation planning.

Synthesis and applications. Current approaches towards understanding the Population Consequences of Disturbance (PCoD) often must rely on expert opinion due to data deficiency. Our model provides an empirical method for linking behaviour to energetics, which is critical for managers to make informed decisions on actions that may affect marine mammal species. Furthermore, our model is applicable to other forms of disturbance, such as vessel traffic or seismic exploration, and our scaling approach enables risk projections for understudied species.

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Intrinsic value and educational value
Authors: Gatley Jane
Published: May 2021

In this paper, I ask whether educational value is determined in any way by intrinsic value. The aim of the paper is to explore whether appeals to the intrinsic value of an activity or state of affairs can justify proposed educational value. I turn to Korsgaard's work on the concept of intrinsic value to cast light on the relationship between intrinsic value and educational value. Korsgaard claims that the often held distinction between intrinsic and instrumental value conflates two separate distinctions. These are the intrinsic/extrinsic value distinction and the final/instrumental value distinction. These two distinctions will be considered with regard to literature that appeals to intrinsic value. The distinctions between intrinsic/extrinsic value and final/instrumental value will be used to clarify puzzles which arise when philosophers of education use the concept of intrinsic value to make claims about educational value. I argue that the intrinsic/extrinsic value distinction has little bearing on an activity's educational value. The instrumental/final value distinction is relevant, but does not imply that activities with final value are any more educationally valuable than those with instrumental value. I conclude that, regardless of the distinction being appealed to, general intrinsic value has little bearing on educational value.
The flourishing child
Authors: Wolbert Lynne , de Ruyter Doret , Schinkel Anders
Published: May 2021

This paper aims to offer conceptual clarification on the use of the concept of human flourishing with regard to children. We will argue that the concept can meaningfully be applied to parts of human lives, specifically one's childhood, and discuss when we can meaningfully speak of a flourishing child. Viewing children's lives in terms of whether they are flourishing may be able to help us understand and articulate in which ways a child's life may go better or worse. This is relevant, firstly, to the overall evaluation of people's lives, and secondly, because a flourishing childhood could be instrumentally necessary for adult flourishing. But, most importantly, childhood is a period of life that is good in itself irrespective of its contribution to adult flourishing, that is, being able to be a child has intrinsic goodness. Children have particular characteristics that can optimally function in childhood. While these contribute to the overall evaluation of a flourishing life, they are not regarded as valuable only because of this contribution.
Patient experience of telephone consultations in gynaecology: a service evaluation
Authors: Khan Z M , Kershaw V , Madhuvrata P , Radley S C , Connor M E
Published: May 2021

Objective

To investigate patient perspective of telephone consultations (TCs) in gynaecology and identify which patients benefit most from a telemedicine system.

Design

Service evaluation.

Setting

Gynaecology outpatient services at a tertiary referral hospital.

Population

Patients who received a TC during May and June 2020.

Methods

Postal questionnaire combining three validated tools: QQ‐10, Patient Enablement Index (PEI) and National Health Service Friends and Family Test (NHS‐FFT). Quantitative data and free text responses were analysed.

Main outcome measures

Responses to QQ‐10, PEI and NHS‐FFT.

Results

In total, 1307 patients were contacted and 504 patients responded (39%). Most (89%) described their experience as ‘Very good’ or ‘Good’ (NHS‐FFT). Positive themes from responses included ‘convenience’, ‘effectiveness’ and ‘equivalent care’. QQ‐10 responses demonstrated a high Value score of 79 (0–100) and a low Burden score of 15. PEI scores suggested that most patients felt better or much better able to understand and cope with their condition following TC. The majority of patients (77%) would ‘Strongly agree’ or ‘Mostly agree’ to a repeat TC. Regarding patient outcomes, 21% were discharged and 71% required follow up. Menopause, fertility and endometriosis follow‐up clinic patients benefited most from TC. Gynaecology–oncology patients found TC least acceptable.

Conclusion

We report a large questionnaire survey of patient experience of TC in gynaecology. Telemedicine is convenient, acceptable and effective for conducting care in selected groups. TC can support patients in communicating intimate symptoms.

Tweetable abstract

Telephone consultations are a convenient, acceptable and effective medium for conducting patient care in gynaecology.
Association between nutritional and functional status indicators with caregivers' burden in Alzheimer's disease
Authors: Vicente de Sousa Odete , Mendes Joana , Amaral Teresa F.
Published: May 2021

Aim

To investigate the association between nutritional and functional status of Alzheimer's disease patients and caregivers' burden.

Methods

A cross‐sectional study was conducted among 79 community‐dwelling Alzheimer's disease patients living with their caregivers. Caregivers' burden was assessed using the Zarit Burden‐Interview. Multinomial logistic regressions were carried out using caregivers' burden as the dependent variable.

Results

Caregivers' severe overload was strongly associated with weight loss of more than 3 kg during the previous 3 months (OR = 7.34; 95% CI: 2.02‐26.65), lower values of calf girth (OR = 3.20; 95% CI: 1.03‐9.93), sarcopenia status (OR = 3.50; 95% CI: 1.09‐11.22), and lower gait speed values (OR = 3.83; 95% CI: 1.18‐12.47). Otherwise, overweight or obesity (OR = 0.21; 95% CI: 0.05‐0.83), was related to lower odds of higher caregivers' burden.

Conclusion

In community‐dwelling older adults with Alzheimer's disease, the nutritional and functional status impairments were strongly associated with increasing caregivers' burden, whereas overweight conferred protection.
Prognostic impact according to the proportion of the lepidic subtype in stage IA acinar‐predominant lung adenocarcinoma
Authors: Jeon Hyun Woo , Kim Young‐Du , Sim Sung Bo , Moon Mi Hyoung
Published: May 2021

Background

Adenocarcinoma is the most common type of lung cancer and most adenocarcinomas have heterogeneous subtypes. Acinar‐predominant adenocarcinoma is the most common. This study aimed to identify the prognostic impact of other mixed histological subtypes in acinar‐predominant lung adenocarcinoma.

Methods

The medical records of patients with pathological stage IA acinar‐predominant lung adenocarcinoma between January 2010 and April 2016 were reviewed. The patients were divided into two groups according to the proportion of the lepidic subtype, with a cutoff value of 20%, and prognostic factors were analyzed.

Results

A total of 215 patients with stage IA acinar‐predominant adenocarcinoma were reviewed. The 20% or more lepidic subtype group had a low value of SUVmax (p = 0.001), good differentiation (p < 0.001) and a low incidence of the solid histological subtype (p = 0.016). Recurrence was significantly lower in the 20% or more lepidic subtype group (p = 0.008). The disease‐free survival (p = 0.007) and overall survival (p = 0.046) were significantly different between the two groups. Multivariate analysis showed that lymphovascular invasion (p = 0.006) and no or less than 20% lepidic subtype (p = 0.036) were significant prognostic factors for disease‐free survival.

Conclusions

The lepidic proportion may be useful to predict recurrence in acinar‐predominant stage IA lung adenocarcinoma.
Neuronal loss and microgliosis are restricted to the core of Aβ deposits in mouse models of Alzheimer's disease
Authors: Zhang Jing , Wu Na , Wang Shubo , Yao Zitong , Xiao Fuchuan , Lu Jing , Chen Baian
Published: May 2021

Amyloid‐β (Aβ) deposits, pathologic tau, and neurodegeneration are major pathological hallmarks of Alzheimer's disease (AD). The relationship between neuronal loss and Aβ deposits is one of the fundamental questions in the pathogenesis of AD. However, this relationship is controversial. One main reason for the conflicting results may be the confounding effects of pathologic tau, which often coexists with Aβ deposits in the brains of AD patients. To clarify the relationship between neuronal loss and Aβ deposits, mouse models of AD, which develop abundant Aβ deposits in the aged brain without pathologic tau, were used to examine the co‐localization of NeuN‐positive neurons, NF‐H‐positive axons, MBP‐positive myelin sheaths, and Aβ deposits. Neuronal loss, as measured by decreased staining of the neuronal cell body, axon, and myelin sheath, as well as the IBA‐1‐positive microglia, was significantly increased in the core area of cerebral Aβ deposits, but not in adjacent areas. Furthermore, neuronal loss in the core area of cerebral Aβ deposits was correlated with Aβ deposit size. These results clearly indicate that neuronal loss is restricted to the core of Aβ deposits, and this restricted loss probably occurs because the Aβ deposit attracts microglia, which cluster in the core area where Aβ toxicity and neuroinflammation toxicity are restrained. These findings may contribute to our understanding of the relationship between neuronal loss and Aβ deposits in the absence of pathologic tau.
Relapse following bitemporal and high‐dose right unilateral electroconvulsive therapy for major depression
Authors: Jelovac Ana , Kolshus Erik , McLoughlin Declan M.
Published: May 2021

Objective

Electroconvulsive therapy (ECT) is an effective acute treatment for severe and/or medication‐resistant depression but maintaining remission following completion of a course remains a clinical challenge.

Methods

EFFECT‐Dep Trial (ISRCTN23577151) participants with a DSM‐IV major depressive episode who met remission criteria after a randomly assigned course of twice‐weekly brief‐pulse bitemporal (1.5 × seizure threshold) or high‐dose (6 × seizure threshold) right unilateral ECT were monitored for relapse for 12 months. In line with the pragmatic trial design, all patients received treatment‐as‐usual individualised pharmacotherapy during and after ECT; no remitter received continuation ECT.

Results

Of 61 remitters, 24 (39.3%) relapsed, one (1.6%) withdrew from the study while in remission and the remaining 36 (59.0%) stayed well for a year. Most relapses occurred within the first six months, resulting in a cumulative six‐month relapse rate of 31.1%. In a multivariable Cox proportional hazards regression model, older age (p = 0.039) and psychotic features at pre‐ECT baseline (p = 0.037) were associated with a more favourable long‐term prognosis while a greater number of previous depressive episodes (p = 0.028) and bipolar II (but not bipolar I) diagnosis (p = 0.030) were associated with a worse long‐term outcome. Electrode placement and medication resistance prior to ECT had no effect on relapse. Adjusting for covariates, fewer patients treated with lithium relapsed in the overall group (p = 0.008) and in the unipolar depression subgroup (p = 0.027).

Conclusion

Long‐term outcome following high‐dose right unilateral ECT does not differ from bitemporal ECT. Prognosis is particularly favourable in older adults, psychotic depression and patients maintained on lithium.
Prevalence of co‐occurring mental illness and substance use disorder and association with overdose: a linked data cohort study among residents of British Columbia, Canada
Authors: Keen Claire , Kinner Stuart A. , Young Jesse T. , Jang Kerry , Gan Wenqi , Samji Hasina , Zhao Bin , Krausz Michael , Slaunwhite Amanda
Published: May 2021

Aims

To estimate the treated prevalence of mental illness, substance use disorder (SUD) and dual diagnosis and the association between dual diagnosis and fatal and non‐fatal overdose among residents of British Columbia (BC), Canada.

Design

A retrospective cohort study using linked health, income assistance, corrections and death records.

Setting

British Columbia (BC), Canada.

Participants

A total of 921 346 BC residents (455 549 males and 465 797 females) aged 10 years and older.

Measurements

Hospital and primary‐care administrative data were used to identify a history of mental illness only, SUD only, dual diagnosis or no history of SUD or mental illness (2010–14) and overdoses resulting in medical care (2015–17). We calculated crude incidence rates of non‐fatal and fatal overdose by dual diagnosis history. Andersen–Gill and competing risks regression were used to examine the association between dual diagnosis and non‐fatal and fatal overdose, respectively, adjusting for age, sex, comorbidities, incarceration history, social assistance, history of prescription opioid and benzodiazepine dispensing and region of residence.

Findings

Of the 921 346 people in the cohort, 176 780 (19.2%), 6147 (0.7%) and 15 269 (1.7%) had a history of mental illness only, SUD only and dual diagnosis, respectively; 4696 (0.5%) people experienced 688 fatal and 6938 non‐fatal overdoses. In multivariable analyses, mental illness only, SUD only and dual diagnosis were associated with increased rate of non‐fatal [hazard ratio (HR) = 1.8, 95% confidence interval (CI) = 1.6–2.1; HR = 9.0, 95% CI = 7.0–11.5, HR = 8.7, 95% CI = 6.9–10.9, respectively] and fatal overdose (HR = 1.6, 95% CI = 1.3–2.0, HR = 4.3, 95% CI = 2.8–6.5, HR = 4.1, 95% CI = 2.8–6.0, respectively) compared with no history.

Conclusions

In a large sample of residents of British Columbia (Canada), approximately one in five people had sought care for a substance use disorder or mental illness in the past 5 years. The rate of overdose was elevated in people with a mental illness alone, higher again in people with a substance use disorder alone and highest in people with a dual diagnosis. The adjusted hazard rates were similar for people with substance use disorder only and people with a dual diagnosis.
‘A man can only be truly known in drunkenness and war.’ An anthropological perspective on alcohol use during the Portuguese Colonial War
Authors: Gil Calado Vasco
Published: May 2021

Background and aim

To understand the use of psychoactive substances, one must consider the context and the social circumstances in which the substance use occurs. This paper discusses alcohol use from a socio‐cultural perspective, based on the use of alcoholic beverages among the Portuguese servicemen who fought in the Portuguese Colonial War (1961–74).

Method

In‐depth interviews were carried out with 17 former Portuguese soldiers. Simultaneously, extensive bibliographic and documentary research was carried out based on a broad set of biographical and autobiographical texts by former military personnel. Finally, an on‐line survey (n = 210) was conducted among ex‐combatants of the Portuguese Colonial War.

Results

Alcohol drinking among Portuguese servicemen was high during the Portuguese Colonial War. Socio‐cultural factors (such as regarding alcohol consumption as therapeutic and affirming masculinity) explain why alcohol drinking was so intense and frequent, and why repeated drunken behaviour was tolerated and undervalued by the military authorities, who considered it normal and not a health problem or disorder.

Conclusion

The use of alcohol in the Portuguese Colonial War is an empirical example of how what is considered ‘acceptable’, ‘normal’ or ‘pathological’ may depend more on socio‐cultural norms than on objective and measurable criteria, including clinical criteria.
Community‐based smoking cessation treatment for adults with high anxiety sensitivity: a randomized clinical trial
Authors: Smits Jasper A. J. , Zvolensky Michael J. , Rosenfield David , Brown Richard A. , Otto Michael W. , Dutcher Christina D. , Papini Santiago , Freeman Slaton Z. , DiVita Annabelle , Perrone Alex , Garey Lorra
Published: May 2021

Background and Aims

People with anxiety disorders are more likely to smoke and less likely to succeed when they try to quit. Anxiety sensitivity may underlie both phenomena, such that people with high anxiety sensitivity react to interoceptive distress by avoidance. This study aimed to test the efficacy of an exercise program that induced interoceptive distress and thereby created tolerance to this distress in a safe environment.

Design, Setting and Participants

Randomized clinical trial at four YMCA branches in Austin, Texas, USA. Participants [n = 150; 130 (86.7%) white; 101 (67.3%) female; meanage = 38.6, standard deviation (SD)age = 10.4] were adult, daily smokers with high anxiety sensitivity motivated to quit smoking, who reported no regular moderate‐intensity exercise.

Interventions

Participants were assigned a YMCA personal trainer who guided them through a 15‐week intervention aerobic exercise program. Participants assigned to the personalized intervention trained at 60–85% of their heart rate reserve (HRR), whereas participants assigned to the control intervention trained at 20–40% of their HRR. Participants in both groups received standard behavioral support and nicotine replacement therapy.

Measurements

The primary outcome was biologically verified 7‐day point prevalence abstinence (PPA) at 6‐month follow‐up.

Findings

Sixty‐one per cent of participants were available at the 6‐month follow‐up. PPA at 6 months was higher in the personalized intervention than the control intervention [27.6 versus 14.8%; odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.28, 3.80, P = 0.005], assuming missing at random. Anxiety sensitivity declined in both groups with no evidence that this differed between groups.

Conclusions

An exercise program of high intensity increased abstinence from smoking in people with high anxiety sensitivity, but may not have done so by reducing anxiety sensitivity.
Do Female Officers Police Differently? Evidence from Traffic Stops
Authors: Shoub Kelsey , Stauffer Katelyn E. , Song Miyeon
Published: May 2021

Political scientists have increasingly begun to study how citizen characteristics shape whether—and how—they interact with the police. Less is known about how officer characteristics shape these interactions. In this article, we examine how one officer characteristic—officer sex—shapes the nature of police‐initiated contact with citizens. Drawing on literature from multiple fields, we develop and test a set of competing expectations. Using over four million traffic stops made by the Florida State Highway Patrol and Charlotte (North Carolina) Police Department, we find that female officers are less likely to search drivers than men on the force. Despite these lower search rates, when female officers do conduct a search, they are more likely to find contraband and they confiscate the same net amount of contraband as male officers. These results indicate that female officers are able to minimize the number of negative interactions with citizens without losses in effectiveness.
Association between number of replacements and readmissions following total knee and total hip replacements in New South Wales' public hospitals
Authors: Marashi‐Pour Sadaf , Watson Diane E. , Harris Ian A.
Published: May 2021

Background

Total knee and total hip replacement are common and resource‐intensive procedures. Complications are associated with worse outcomes and can add to the health care costs, particularly if associated with readmission. The aims of this study were to inform quality improvement by reporting on the extent of variation in readmissions across public hospitals and investigating the association between hospital volume and readmissions.

Methods

This retrospective population‐based cohort study used linked, admitted patient data for a census of all admissions to public and private hospitals. Adults who had an acute hospitalization for total knee or total hip replacement elective surgery and were discharged alive between 1 July 2015 and 30 June 2018 were included. Hospital volumes and risk standardized readmission ratios were calculated, and readmissions included acute hospitalizations following discharge and returns to acute care from non‐acute settings within 60 days.

Results

In 2015–2018, one in 10 patients were readmitted following total knee or total hip replacement (11.9 and 10.6 per 100 hospitalizations) an increase of 4.9% and 13.1% respectively, compared to 2012–2015. The majority of hospitals had risk standardized readmission ratios no different than expected. The median annual hospital volume was 170 total knee (interquartile range 116–247) and 93 total hip (interquartile range 61–141) procedures with no evidence of a meaningful association between hospital volume and readmissions.

Conclusion

Readmissions rates for total knee and total hip replacements are increasing. While hospital volume varies, it was not associated with readmission after adjusting for risk factors and any non‐linear association.
Umbilical fissure vein, anatomical variation and potential surgical application
Authors: Idrees Marwan , Zhang Leon , Al‐Ogaili Zeyad , Yau Ho‐Cing V. , Zhu Shaun , Jaques Bryon , Foo Jonathan , Mou Lingjun
Published: May 2021

Background

The umbilical fissure vein (UFV) is a hepatic vein that travels within the umbilical fissure (or its proximity), providing venous drainage for hepatic segments 3 and 4. Its preservation carries a potential importance in extended right hemi‐hepatectomy, left lateral segmentectomy and extended segment 2 resections.

Methods

Consecutive 1‐mm slice thickness portovenous phase intravenous contrast computed tomography (CT) scans of the abdomen performed were retrospectively reviewed during the period of June 2019 to July 2019, with two independent investigators investigating the presence of UFV, its course, insertion and relation to the umbilical fissure.

Results

A total of 244 CTs were identified and 186 included. The UFV was identified on 72.8% of participants, 109 (81.4%) drained into the main left hepatic vein, while the remaining ones drained either from the main middle hepatic vein (16.4%) or the bifurcation between main left and middle hepatic vein (2.2%). The veins course lay 2 mm or less along the length of umbilical fissure in 39.5%, while 57.5% ran within 1 cm along the length of the umbilical fissure.

Conclusion

Pre‐operative identification of UFV could assist in operative planning. The vein can be used as a landmark in surgery and should be preserved in left lateral segmentectomy and extended right hepatectomy to avoid parenchymal congestion of remnant segments.
Diet plays a central role in parental self‐treatment of children with Hirschsprung’s disease—a qualitative study
Authors: Telborn Lovisa , Tofft Louise , Kristensson Hallström Inger , Waldenvik Frida , Axelsson Irene , Stenström Pernilla
Published: May 2021

Aim

Hirschsprung's disease is a congenital disorder requiring surgery. Most children operated on for Hirschsprung's disease experience postoperative bowel dysmotility. Although various food is known to influence bowel motility, evidence of diet's role and dietary guidelines in treatment of bowel dysfunction in Hirschsprung's disease is lacking. The aim was to explore parental experiences of dietary effects on bowel function in children with Hirschsprung's disease.

Methods

A qualitative study including three focus groups with ten parents of children with Hirschsprung's disease at a national Hirschsprung's disease centre. Data were analysed through content analysis.

Results

Parents emphasised diet as a strong influencer on their child's bowel function in Hirschsprung's disease. They expressed great concerns about their responsibility and strived hard to explore and adjust dietary habits to control the child's bowel function. Families’ daily and social lives were influenced by the child's diet and bowel function. The parents desired dietary support and guidelines to improve their confidence in self‐treatment of Hirschsprung's disease.

Conclusion

Dietary habits play a key role in parental self‐treatment of bowel function in their children with Hirschsprung's disease. Dietary guidelines for patients with Hirschsprung's disease are anticipated.
The impact of rifampicin on the pharmacokinetics of fuzuloparib in healthy Chinese male volunteers
Authors: Zhang Qiao , Kai Jiejing , Zhai You , Xu Nana , Shentu Jianzhong , Zhang Yanyan , Liang Yanjuan , Wang Yuya , Wu Lihua
Published: May 2021

Aims

This clinical study was conducted to evaluate the impact of rifampicin on the pharmacokinetics of fuzuloparib.

Methods

In this single‐centre, single‐arm, open‐label, fixed‐sequence study, healthy male subjects took a single 50 mg dose of fuzuloparib on two separate occasions: the first was on Day 1 as monotherapy, and the second was on Day 12 after oral administration of rifampicin 600 mg once daily for 8 days. Series of blood samples were obtained before and after fuzuloparib administration at different time points: pre‐dose, and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post‐dose. All samples were examined using liquid chromatography with tandem mass spectrometry. PK parameters were estimated by using a non‐compartmental method with Phoenix WinNonlin software. Safety was assessed by monitoring for changes in vital signs and laboratory tests, physical examinations, and incidences of adverse events (AEs).

Results

A total of 16 Chinese male subjects were enrolled. Of these, 16 and 15 cases were evaluable for PK analysis following administration with fuzuloparib alone and pretreatment with rifampicin, respectively. Pretreatment with rifampicin resulted in a statistically significant reduction in the systemic exposure to fuzuloparib. The treatment ratio and 90% confidence intervals (CIs) for AUC0‐∞ and Cmax were 0.10 (0.095–0.115) and 0.32 (0.281–0.365), respectively. A single administration of fuzuloparib after multiple oral dosing of rifampicin was well‐tolerated, without severe AEs.

Conclusion

The exposure of fuzuloparib was dramatically decreased when pretreated with rifampicin. Strong CYP3A4 inducers should be avoided during fuzuloparib treatment.
Society for Endocrinology UK Guidance on the initial evaluation of a suspected difference or disorder of sex development (Revised 2021)
Authors: Ahmed S. Faisal , Achermann John , Alderson Julie , Crouch Naomi S. , Elford Sue , Hughes Ieuan A. , Krone Nils , McGowan Ruth , Mushtaq Talat , O’Toole Stuart , Perry Leslie , Rodie Martina E. , Skae Mars , Turner Helen E.
Published: May 2021

It is paramount that any child or adolescent with a suspected difference or disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD and is discussed with the regional DSD service. In most cases, the paediatric endocrinologist within this service acts as the first point of contact but involvement of the regional multidisciplinary service will also ensure prompt access to specialist psychology and nursing care. The underlying pathophysiology of DSD and the process of delineating this should be discussed with the parents and affected young person with all diagnostic tests undertaken in a timely fashion. Finally, for rare conditions such as these, it is imperative that clinical experience is shared through national and international clinical and research collaborations.
Comparison of complications and visual outcomes between big‐bubble deep anterior lamellar keratoplasty and penetrating keratoplasty for fungal keratitis
Authors: Chen Xiunian , Li Xiaofeng , Zhang Xiaoyu , Guo Xiaoting , Qi Xiaolin , Li Suxia , Shi Weiyun , Gao Hua
Published: May 2021

Background

To compare the postoperative complications and visual outcomes of big‐bubble deep anterior lamellar keratoplasty (BB‐DALK) and penetrating keratoplasty (PK) for fungal keratitis (FK).

Methods

This retrospective study included 94 cases of BB‐DALK for FK and 161 cases of PK for FK from a tertiary ophthalmology care centre.

Results

The most common FK pathogens were Fusarium (n = 84, 32.9%) and Aspergillus (n = 67, 26.3%). The recurrence rates after BB‐DALK and PK were 3.2 and 5%, respectively (p = 0.723). The follow‐up duration was 31.9 ± 15.8 months in the BB‐DALK group and 33.9 ± 15.0 months in the PK group. The immune rejection rate was significantly lower in the BB‐DALK group than in the PK group (1.1 vs. 18.6%, p < 0.001), as was the incidence of secondary glaucoma (p = 0.018). Endothelial cell density in the BB‐DALK group tended to be stable at postoperative month 6, whereas the PK group still attenuated at a hyper‐physiological rate. Postoperative best‐corrected visual acuity (BCVA) significantly improved in both groups (p < 0.001). No significant difference between‐group was observed in BCVA, refractive cylinder, and spherical equivalent postoperatively.

Conclusion

Big‐bubble DALK is a useful and safe alternative to PK for medically uncontrolled FK.
Reduced fracture load of dental implants after implantoplasty with different instrumentation sequences. An in vitro study
Authors: Jorio Isabelle C. , Stawarczyk Bogna , Attin Thomas , Schmidlin Patrick R. , Sahrmann Philipp
Published: May 2021

Objectives

To assess the mechanical stability of implants after implantoplasty and thermocyclic loading, the residual thickness of the instrumented areas and neighbouring tooth injury due to implantoplasty.

Materials and Methods

Using a phantom head simulator and maxillary model implants were subjected to an implantoplasty procedure. Thirty implants were randomly assigned to receive one of three instrumentation sequences. After instrumentation, injury on neighbouring teeth was assessed. Instrumented implants and non‐instrumented controls were subjected to 1.2 million cycles of thermo‐mechanical loading in a chewing machine. Afterwards, maximum fracture load for all implants and an additional five pristine control implants was tested.

Results

Generally, damage of neighbour teeth was a frequent finding (33 ± 56% of all cases) with considerable inter‐group differences. No considerable inter‐group difference for the residual implant thickness was found for different areas assessed. No implant fractured during cyclic loading. Fracture load was reduced after cyclic loading of uninstrumented implants from 2,724 ± 70 N to 2,299 ± 127 N, and after implantoplasty to 1,737 ± 165 N, while no effect by the instrumentation sequence could be observed.

Conclusions

Both implantoplasty and cyclic loading were shown to reduce the implants' maximum bending strength. Cyclic loading in a laboratory masticator, simulating a five‐year equivalent of chewing, did not result in fractured implants. Since neighbouring tooth injury was assessed often, care should be taken with the selection of suitable instruments.
Fine needle aspiration cytology of a level IIB lymph node—what's your differential?
Authors: Mistry Sabina Kaur , Pratap Rohit , Maddox Anthony
Published: May 2021

A wide variety of neoplasms can present with a lump in the neck and not all are lymphomas. This case demonstrates classical features of an uncommon entity.