bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving precision and power in randomized trials for COVID‐19 treatments using covariate adjustment, for binary, ordinal, and time‐to‐event outcomes
Authors: Benkeser David , Díaz Iván , Luedtke Alex , Segal Jodi , Scharfstein Daniel , Rosenblum Michael
Published: September 2020

Time is of the essence in evaluating potential drugs and biologics for the treatment and prevention of COVID‐19. There are currently 876 randomized clinical trials (phase 2 and 3) of treatments for COVID‐19 registered on clinicaltrials.gov. Covariate adjustment is a statistical analysis method with potential to improve precision and reduce the required sample size for a substantial number of these trials. Though covariate adjustment is recommended by the U.S. Food and Drug Administration and the European Medicines Agency, it is underutilized, especially for the types of outcomes (binary, ordinal, and time‐to‐event) that are common in COVID‐19 trials. To demonstrate the potential value added by covariate adjustment in this context, we simulated two‐arm, randomized trials comparing a hypothetical COVID‐19 treatment versus standard of care, where the primary outcome is binary, ordinal, or time‐to‐event. Our simulated distributions are derived from two sources: longitudinal data on over 500 patients hospitalized at Weill Cornell Medicine New York Presbyterian Hospital and a Centers for Disease Control and Prevention preliminary description of 2449 cases. In simulated trials with sample sizes ranging from 100 to 1000 participants, we found substantial precision gains from using covariate adjustment–equivalent to 4–18% reductions in the required sample size to achieve a desired power. This was the case for a variety of estimands (targets of inference). From these simulations, we conclude that covariate adjustment is a low‐risk, high‐reward approach to streamlining COVID‐19 treatment trials. We provide an R package and practical recommendations for implementation.
Collective cancer cell invasion in contact with fibroblasts through integrin‐α5β1/fibronectin interaction in collagen matrix
Authors: Miyazaki Kaoru , Togo Shinsaku , Okamoto Reiko , Idiris Alimjan , Kumagai Hiromichi , Miyagi Yohei
Published: September 2020

Interaction of cancer cells with cancer‐associated fibroblasts (CAFs) plays critical roles in tumor progression. Recently we proposed a new tumor invasion mechanism in which invasive cancer cells individually migrate on elongate protrusions of CAFs (CAF fibers) in 3‐D collagen matrix. In this mechanism, cancer cells interact with fibronectin fibrils assembled on CAFs mainly through integrin‐α5β1. Here we tested whether this mechanism is applicable to the collective invasion of cancer cells, using two E‐cadherin‐expressing adenocarcinoma cell lines, DLD‐1 (colon) and MCF‐7 (breast). When hybrid spheroids of DLD‐1 cells with CAFs were embedded into collagen gel, DLD‐1 cells collectively but very slowly migrated through the collagen matrix in contact with CAFs. Epidermal growth factor and tumor necrosis factor‐α promoted the collective invasion, possibly by reducing the E‐cadherin junction, as did the transforming growth factor‐β inhibitor SB431542 by stimulating the outgrowth of CAFs. Transforming growth factor‐β itself inhibited the cancer cell invasion. Efficient collective invasion of DLD‐1 cells required large CAF fibers or their assembly as stable adhesion substrates. Experiments with function‐blocking Abs and siRNAs confirmed that DLD‐1 cells adhered to fibronectin fibrils on CAFs mainly through integrin‐α5β1. Anti‐E‐cadherin Ab promoted the single cell invasion of DLD‐1 cells by dissociating the E‐cadherin junction. Although the binding affinity of MCF‐7 cells to CAFs was lower than DLD‐1, they also collectively invaded the collagen matrix in a similar fashion to DLD‐1 cells. Our results suggest that the direct interaction with CAFs, as well as environmental cytokines, contributes to the collective invasion of cancers.
The fence technique: Autogenous bone graft versus 50% deproteinized bovine bone matrix / 50% autogenous bone graft—A clinical double‐blind randomized controlled trial
Authors: Merli Mauro , Nieri Michele , Mariotti Giorgia , Merli Marco , Franchi Lorenzo , Quiroga Souki Bernardo
Published: September 2020

Objectives

The aim of this short‐term double‐blind, parallel, randomized clinical trial was to compare bone augmentation grafting with 100% autogenous bone (AB) or 50% deproteinized bovine bone matrix (DBBM)/ 50% autogenous bone (BOAB) using a guided bone regeneration procedure, the fence technique, in a two‐stage implant placement.

Material and methods

Partially edentulous patients with extensive three‐dimensional osseous defects were included in this study. The main outcome measure was the differences in bone volume from pre‐surgery (T1) to 6 months post‐surgery (T2). Bone height, chair‐time, pain, functional limitation, and complications were also assessed.

Results

Fifteen patients were allocated to the AB group and 15 patients to the BOAB group. The difference in bone volume from T1 to T2 was 648 mm3 for the AB group and 869mm3 for the BOAB group (difference between groups 221 mm3, 95% CI from −363 to 804, p = .442). The surgery pain VAS was 1.6 for the AB group and 2.3 for the BOAB group (difference between groups 0.8, 95% CI from 0.0 to 1.5, p = .045 favoring the AB group). The height difference in bone from T1 to T2 was 2.2 mm for the AB group and 3.7 mm for the BOAB group (difference between groups 1.5mm, 95% CI from 0.1 to 2.9, p = .038 favoring the BOAB group). For complications, chair‐time, post‐surgery pain, and functional limitation, there were no differences between AB and BOAB.

Conclusions

No significant differences, except for surgery pain VAS and difference in bone height, were observed in this trial comparing grafting with AB or BOAB.
Approaches to interdisciplinary mixed methods research in land‐change science and environmental management
Authors: Kinnebrew Eva , Shoffner Elizabeth , Farah‐Pérez Aldo , Mills‐Novoa Megan , Siegel Katherine
Published: September 2020

Combining qualitative and quantitative methods and data is crucial to understanding the complex dynamics and often interdisciplinary nature of conservation. Many conservation scientists use mixed methods, but there are a variety of mixed methods approaches, a lack of shared vocabulary, and few methodological frameworks. We reviewed articles from 2 conservation‐related fields that often incorporate qualitative and quantitative methods: land‐change science (n = 16) and environmental management (n = 16). We examined how authors of these studies approached mixed methods research by coding key methodological characteristics, including relationships between method objectives, extent of integration, iterative interactions between methods, and justification for use of mixed methods. Using these characteristics, we created a typology with the goal of improving understanding of how researchers studying land‐change science and environmental management approach interdisciplinary mixed methods research. We identified 5 types of mixed methods approaches, which we termed simple nested, informed nested, simple parallel, unidirectional synthesis, and bidirectional synthesis. Methods and data sources were often used to address different research questions within a project, and only around half of the reviewed papers methodologically integrated different forms of data. Most authors used one method to inform the other, rather than both informing one another. Very few articles used methodological iteration. Each methodological type has certain epistemological implications, such as the disciplinary reach of the research and the capacity for knowledge creation through the exchange of information between distinct methodologies. To exemplify a research design that can lead to multidimensional knowledge production, we provide a methodological framework that bidirectionally integrates and iterates qualitative and quantitative methods.
Epidemiology of haemorrhoids and publicly funded excisional haemorrhoidectomies in New Zealand (2007–2016): a population‐based cross‐sectional study
Authors: Xia Weisi , Barazanchi Ahmed W. H. , Coomarasamy Christin , Jin James , Maccormick Andrew D. , Sammour Tarik , Hill Andrew G.
Published: September 2020

Aim

Haemorrhoids are frequently encountered by the general or colorectal surgeon. Although a benign disease, those with symptomatic, advanced grades frequently require excisional haemorrhoidectomy for definitive management. Despite their widespread nature, the epidemiological burden of haemorrhoids and haemorrhoidectomies on populations is not well described. This study seeks to establish the incidence of both haemorrhoids diagnosed and haemorrhoidectomies performed in New Zealand.

Method

This is a population‐based cross‐sectional study examining the incidence of all patients who were newly diagnosed with haemorrhoids in New Zealand public hospital outpatient clinics and those who received excisional haemorrhoidectomy in New Zealand public hospitals from 2007 to 2016. Data were extracted and linked using the New Zealand National Minimum Dataset and the National Non‐Admitted Patient Collection. Variables collected included age group, sex, ethnicity and geographical location.

Results

A total of 46 095 recorded diagnoses of haemorrhoids were made, with a total of 18 739 haemorrhoidectomies in the 10‐year period recorded. The incidence rate of diagnosis increased from 84.6 to 120.5 per 100 000 and the incidence rate of haemorrhoidectomies performed from 30.4 to 51.1 per 100 000, a significantly increased annual incidence. There was a unimodal peak prevalence in the fifth decade of life with women more affected. Europeans formed the largest group affected, with Asians showing the highest rate of increased incidence.

Conclusion

There is an increasing incidence of patients with symptomatic haemorrhoids presenting to the New Zealand public healthcare system, with a preponderance in working age adults, especially women.
Pelvic exenteration combined with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for advanced primary or recurrent colorectal cancer with peritoneal metastases
Authors: Brown Kilian G. M. , Ansari Nabila , Solomon Michael J. , Austin Kirk K. S. , Hamilton Auerilius E. R. , Young Christopher J.
Published: September 2020

Aim

The aim was to report early outcomes of six patients who underwent combined pelvic exenteration (PE), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced or recurrent colorectal cancer with colorectal peritoneal metastases at a single centre. The literature contains limited data on the safety and oncological outcomes of patients who undergo this combined procedure.

Methods

Six patients who underwent combined PE, CRS and HIPEC at Royal Prince Alfred Hospital, Sydney, between January 2017 and February 2020 were identified and included. Data were extracted from prospectively maintained databases.

Results

Three patients underwent surgery for advanced primary rectal cancer, while two patients had recurrent sigmoid cancer and one had recurrent rectal cancer. All patients had synchronous peritoneal metastases. Two patients required total PE and two patients had a central (bladder‐sparing) PE. The median peritoneal carcinomatosis index was 6 (range 3–12) and all patients underwent a complete cytoreduction. The median operating time was 702 min (range 485–900) and the median blood loss was 1650 ml (range 700–12,000). The median length of intensive care unit and hospital stay was 4.5 and 25 days, respectively. There was no inpatient, 30‐day or 90‐day mortality. Three patients (50%) experienced a major (Clavien–Dindo III/IV) complication. At a median follow‐up of 11.5 months (range 2–18 months), two patients died with recurrent disease, one patient was alive with recurrence, while three patients remain alive and disease‐free. Of the three patients who developed recurrent disease, one had isolated pelvic recurrence, one had pelvic and peritoneal recurrences and one had bone metastases.

Conclusion

Early results from this initial experience with simultaneous PE, CRS and HIPEC suggest that this combined procedure is safe and feasible; however, the long‐term oncological and quality of life outcomes require further investigation.
Intra‐operative assessment of left‐sided colorectal anastomotic integrity: a systematic review of available techniques
Authors: Clifford Rachael E. , Fowler Hayley , Manu Nicola , Sutton Paul , Vimalachandran Dale
Published: September 2020

Aim

Anastomotic leak (AL) after colorectal resection is associated with increased rates of morbidity and mortality: potential permanent stoma formation, increased local recurrence, reduced cancer‐related survival, poor functional outcomes and associated quality of life. Techniques to reduce leak rates are therefore highly sought.

Method

A literature search was performed for published full text articles using PubMed, Cochrane and Scopus databases with a focus on colorectal surgery 1990–2020. Additional papers were detected by scanning references of relevant papers.

Results

A total of 53 papers were included after a thorough literature search. Techniques assessed included leak tests, endoscopy, perfusion assessment and fluorescence studies. Air‐leak testing remains the most commonly used method across Europe, due to ease of reproducibility and low cost. There is no evidence that this reduces the leak rate; however, identification of a leak intra‐operatively provides the opportunity for either suture reinforcement or formal takedown with or without re‐do of the anastomosis and consideration of diversion. Suture repair alone of a positive air‐leak test is associated with an increased AL rate. The use of fluorescence studies to guide the site of anastomosis has demonstrated reduced leak rates in distal anastomoses, is safe, feasible and has a promising future.

Conclusion

Although over reliance on any assessment tool should be avoided, intra‐operative techniques with the aim of reducing AL rates are increasingly being employed. Standardization of these methods is imperative for routine use. However, in the interim it is recommended that all anastomoses should be assessed intra‐operatively for mechanical failure, particularly distal anastomoses.
The palliative care needs of lung transplant candidates
Authors: Pawlow Patricia C. , Blumenthal Nancy P. , Christie Jason D. , Matura Lea Ann , Courtright Katherine R. , Aryal Subhash , Ersek Mary
Published: September 2020

Background

Little is known about the palliative care needs of patients awaiting lung transplantation. The aim of this study was to describe these needs in patients undergoing evaluation for or awaiting lung transplantation.

Methods

Cross‐sectional survey using an adapted version of the Needs at the End‐of‐life Screening Tool (NEST‐13) at a US‐based transplant program.

Results

Among the 111 participants, 83.5% were White, 60.0% were female, and almost three‐quarters had either restrictive or obstructive lung disease. The greatest palliative care needs included difficulty being physically active (mean: 7.9/10; SD: 2.6; median: 9.0), physical symptoms (mean: 7.4/10; SD: 2.6; median: 8.0), missing work due to illness (mean: 6.2/10; SD: 4.0; median: 8.0), and concerns that life might end (mean: 5.1/10; SD: 3.6; median: 5.0). Participants reported that religious/spiritual beliefs contribute to their sense of purpose (mean: 4.1/10; SD: 3.9) but had few unmet needs in this area (mean: 0.9/10; median: 0.0). Only 6.4% reported seeing a palliative care specialist, and 48.2% were unsure what a palliative care specialist is.

Conclusion

There are substantial palliative care needs among lung transplant candidates, particularly physical symptoms and end‐of‐life concerns. These findings support integrating palliative care and end‐of‐life discussions in the management of lung transplant candidates.
Habitat sampler—A sampling algorithm for habitat type delineation in remote sensing imagery
Authors: Neumann Carsten
Published: September 2020

Aim

The management of habitats for the conservation and restoration of biodiversity in protected area networks requires an appropriate monitoring to increase our understanding of processes and dynamics in managed ecosystems. Remote sensing offers a unique potential for the derivation of coherent spatiotemporal information to report on natural or management‐induced habitat change. However, the methods used for the delineation of habitat types in remote sensing imagery depend on the extensive process of ground truth sampling as reference to construct image classifiers. In fact, the number of required reference samples is intrinsically unknown in complex scenes due to the heterogeneity of varying habitat conditions. Thus, most classifiers are not transferable in retrospective image analysis or between different ecosystems that is, however, required for an operational use of remote sensing‐based monitoring systems.

Innovation

A new procedure is introduced that autonomously generates representative reference samples for a predictive modelling of habitat type probabilities. The procedure, termed Habitat Sampler, is provided as a tool that can be applied to any image input that display vegetation structures and dynamics on multiple temporal and spatial scales. The Habitat Sampler provides many labelled point locations for the training of image classifiers and enables a fast and easy to implement model transfer for the delineation of habitat dynamics in various ecosystems.

Main conclusions

The Habitat Sampler outperforms standard machine learning classifiers when the distribution of reference samples is unknown or insufficient. It was shown that particularly in retrospective image analyses patterns of successional and cyclic habitat development can be mapped for large heathland areas. The procedure is feasible for application in biodiversity conservation monitoring using various habitat typologies that are associated over ecosystem processes, particularly to report on protected area networks using cost‐free satellite imagery.
The impact of preterm birth on the life course: assessment challenges and future directions
Authors: Jaekel Julia
Published: September 2020

This commentary is on the original article by Darlow et al. on pages 1423–1428 of this issue.
Cerebro‐renal interaction and stroke
Authors: Shah Birva , Jagtap Priya , Sarmah Deepaneeta , Datta Aishika , Raut Swapnil , Sarkar Ankan , Bohra Mariya , Singh Upasna , Baidya Falguni , Kalia Kiran , Borah Anupom , Dave Kunjan R. , Yavagal Dileep R. , Bhattacharya Pallab
Published: September 2020

Stroke is an event causing a disturbance in cerebral function leading to death and disability worldwide. Both acute kidney injury and chronic kidney disease (CKD) are associated with an increased risk of stroke and cerebrovascular events. The underlying mechanistic approach between impaired renal function and stroke is limitedly explored and has attracted researchers to learn more for developing therapeutic intervention. Common risk factors such as hypertension, hyperphosphatemia, atrial fibrillation, arteriosclerosis, hyperhomocysteinemia, blood‐brain barrier disruption, inflammation, etc. are observed in the general population, but are high in renal failure patients. Also, risk factors like bone mineral metabolism, uremic toxins, and anemia, along with the process of dialysis in CKD patients, eventually increases the risk of stroke. Therefore, early detection of risks associated with stroke in CKD is imperative, which may decrease the mortality associated with it. This review highlights mechanisms by which kidney dysfunction can lead to cerebrovascular events and increase the risk of stroke in renal impairment.
Inflammatory pain in peripheral tissue depends on the activation of the TNF‐α type 1 receptor in the primary afferent neuron
Authors: de Magalhães Silviane F. , Manzo Luis P. , de Faria Felipe M. , de Oliveira‐Fusaro Maria C. , Nishijima Catarine M. , Vieira Willians F. , Bonet Ivan J. M. , dos Santos Gilson G. , Tambeli Claudia H. , Parada Carlos A.
Published: September 2020

The mechanism underlying the role of tumor necrosis factor alpha (TNF‐α) in the development of inflammatory hyperalgesia has been extensively studied, mainly the role of TNF‐α in the release of pro‐inflammatory cytokines. The current concept relies in the fact that TNF‐α stimulates the cascade release of other pro‐inflammatory cytokines, such as IL‐1β, IL‐6, and IL‐8 (CINC‐1 in rats), triggering the release of the final inflammatory mediator prostaglandin E2(PGE2) and sympathetic amines that directly sensitize the nociceptors. However, this may not be the sole mechanism involved as the blockade of TNF‐α synthesis by thalidomide prevents hyperalgesia without interrupting the synthesis of IL‐1β, IL‐6, and CINC‐1. Therefore, we hypothesized that activation of TNF‐α receptor type 1 (TNFR1) by TNF‐α increases nociceptors’ susceptibility to the action of PGE2and dopamine. We have found out that intrathecal administration of oligodeoxynucleotide‐antisense (ODN‐AS) against TNFR1 or thalidomide prevented carrageenan‐induced hyperalgesia. The co‐administration of TNF‐α with a subthreshold dose of PGE2or dopamine that does not induce hyperalgesia by itself in the hind paw of Wistar rats pretreated with dexamethasone (to prevent the endogenous release of cytokines) induced a robust hyperalgesia that was prevented by intrathecal treatment with ODN‐AS against TNFR1. We consider that the activation of neuronal TNFR1 by TNF‐α decisively increases the susceptibility of the peripheral afferent neuron to the action of final inflammatory mediators – PGE2and dopamine – that ultimately induce hyperalgesia. This mechanism may also underlie the analgesic action of thalidomide.
Altered prefrontal cortex responses in older adults with subjective memory complaints and dementia during dual‐task gait: An fNIRS study
Authors: Teo Wei‐Peng , Rantalainen Timo , Nuzum Nathan , Valente Leah , Macpherson Helen
Published: September 2020

People with cognitive impairments show deficits during physical performances such as gait, in particular during cognitively challenging conditions (i.e. dual‐task gait [DTG]). However, it is unclear if people at risk of dementia, such as those with subjective memory complaints (SMC), also display gait and central deficits associated with DTG. In this study, we investigated the effects of single‐ and dual‐task gait (STG and DTG), on left prefrontal cortex (PFC) activation in elderly people with subjective memory complaints (SMC) and Dementia. A total of 58 older adults (aged 65–94 years; 26 Healthy; 23 SMC; 9 Dementia) were recruited. Gait spatiotemporal characteristics (i.e. stride velocity and length) were assessed using an instrumented walkway during STG and DTG. Single‐channel functional near‐infrared spectroscopy over the left PFC was used to measure changes in oxyhaemoglobin (O2Hb) during gait. Stride velocity and length during STG (all p < .05) and DTG (all p < .000) were significantly impaired in people with Dementia compared to Healthy and SMC individuals. No differences were observed between Healthy and SMC. For STG, a greater increase in O2Hb (p < .05) was observed in those with Dementia compared to the Healthy and SMC, while no differences were observed between Healthy and SMC. A significant increase and decline in O2Hb was observed during DTG in the SMC and Dementia groups, respectively, compared to Healthy. Our findings indicate an altered pattern of cerebral haemodynamic response of the left PFC in DTG in people with SMC and Dementia, which may suggest that central changes precede functional impairments in people with SMC.
Balancing Conflicting Goals in Interorganizational Collaborations in the Pharmaceutical Industry: A Contractual Dynamics View
Authors: Vedel Jane Bjørn
Published: September 2020

This study examines how contractual dynamics allow company managers to balance conflicting goals in interorganizational collaborations. While the literature on contractual governance has mainly investigated single contracts through a static view, this paper advances a ‘contractual dynamics view’ to explore how the dynamics of related contracts allow managers to balance conflicting goals in interorganizational collaborations. The study involves a longitudinal case study of a collaboration among a pharmaceutical company, a biotech firm, a foundation, and a university. Exploring contractual dynamics from the perspective of the pharmaceutical company's managers, the study finds that related contracts allowed them to balance goals through an unfolding process of differentiating and integrating goals and responding to changing goals. By presenting a ‘contractual dynamics view,’ the study advances understanding of contractual governance and offers implications for management.
Multiple sclerosis and COVID‐19: How many are at risk?
Authors: Bsteh Gabriel , Bitschnau Christina , Hegen Harald , Auer Michael , Di Pauli Franziska , Rommer Paulus , Deisenhammer Florian , Berger Thomas
Published: September 2020

Background and Purpose

The coronavirus disease 2019 (COVID‐19) pandemic challenges neurologists in counseling multiple sclerosis (MS) patients with respect to their risk for and by severe acute respiratory syndrome coronavirus 2 and in guiding disease‐modifying treatment (DMT). The objective was to determine the frequency and distribution of currently known risk factors for COVID‐19 mortality in an MS population.

Methods

Multiple sclerosis patients with at least one complete case report between January 1, 2015 and December 31, 2019 from the Innsbruck MS database were cross‐sectionally included. Frequencies of currently estimated COVID‐19 mortality risk factors were analyzed, and the cumulative risk was calculated by a recently developed score. For every risk group, the proportions of patients under DMT and immunosuppressive treatment were determined.

Results

Of 1931 MS patients, 63.4% had low risk of COVID‐19 mortality, 26% had mild risk, 8.8% had a moderate risk, whereas a combined 0.9% had high or very high risk of COVID‐19 mortality. Of the patients at high or very high risk, only one patient received DMT and none had an immunosuppressive therapy.

Conclusions

In a population‐based MS cohort, the proportion of patients at high risk of COVID‐19 mortality is below 1%. Importantly, the vast majority of these MS patients did not receive any DMT.
Effects of caffeine on mating behavior and sperm precedence in Tribolium castaneum
Authors: Yuhao Ji , Ryuji Yuki , Matsumura Kentarou , Miyatake Takahisa
Published: September 2020

Biogenic amines such as dopamine are physiologically neuroactive substances that affect behavioral and physiological traits in invertebrates, and it has long been known that these substances affect mating behavior in insects. Caffeine is a dopamine activator and thus enhances dopamine receptor activity. However, the effects of caffeine intake on insect mating behavior have been largely unexplored. Therefore, we examined the effect of caffeine on mating behavior in the red flour beetle Tribolium castaneum. Caffeine, which activates dopamine, affected the mating behavior of T. castaneum males. Males who orally ingested caffeine courted faster than males who did not, resulting in faster mounting of females and less time to a male's external aedeagus protrusion. However, the present results showed no difference in sperm precedence measured as a P2 value between males fed caffeine and males not fed caffeine. We discuss the effects of caffeine on insect mating and the possibility that caffeine consumption may cause males to mate with more females in the laboratory.
Reconciling seascape genetics and fisheries science in three codistributed flatfishes
Authors: Vandamme Sara , Raeymaekers Joost A. M. , Maes Gregory E. , Cottenie Karl , Calboli Federico C. F. , Diopere Eveline , Volckaert Filip A. M.
Published: September 2020

Uncertainty hampers innovative mixed‐fisheries management by the scales at which connectivity dynamics are relevant to management objectives. The spatial scale of sustainable stock management is species‐specific and depends on ecology, life history and population connectivity. One valuable approach to understand these spatial scales is to determine to what extent population genetic structure correlates with the oceanographic environment. Here, we compare the level of genetic connectivity in three codistributed and commercially exploited demersal flatfish species living in the North East Atlantic Ocean. Population genetic structure was analysed based on 14, 14 and 10 neutral DNA microsatellite markers for turbot, brill and sole, respectively. We then used redundancy analysis (RDA) to attribute the genetic variation to spatial (geographical location), temporal (sampling year) and oceanographic (water column characteristics) components. The genetic structure of turbot was composed of three clusters and correlated with variation in the depth of the pycnocline, in addition to spatial factors. The genetic structure of brill was homogenous, but correlated with average annual stratification and spatial factors. In sole, the genetic structure was composed of three clusters, but was only linked to a temporal factor. We explored whether the management of data poor commercial fisheries, such as in brill and turbot, might benefit from population‐specific information. We conclude that the management of fish stocks has to consider species‐specific genetic structures and may benefit from the documentation of the genetic seascape and life‐history traits.
Does economic optimisation explain LAI and leaf trait distributions across an Amazon soil moisture gradient?
Authors: Flack‐Prain Sophie , Meir Patrick , Malhi Yadvinder , Smallman Thomas L. , Williams Mathew
Published: September 2020

Leaf area index (LAI) underpins terrestrial ecosystem functioning, yet our ability to predict LAI remains limited. Across Amazon forests, mean LAI, LAI seasonal dynamics and leaf traits vary with soil moisture stress. We hypothesise that LAI variation can be predicted via an optimality‐based approach, using net canopy C export (NCE, photosynthesis minus the C cost of leaf growth and maintenance) as a fitness proxy. We applied a process‐based terrestrial ecosystem model to seven plots across a moisture stress gradient with detailed in situ measurements, to determine nominal plant C budgets. For each plot, we then compared observations and simulations of the nominal (i.e. observed) C budget to simulations of alternative, experimental budgets. Experimental budgets were generated by forcing the model with synthetic LAI timeseries (across a range of mean LAI and LAI seasonality) and different leaf trait combinations (leaf mass per unit area, lifespan, photosynthetic capacity and respiration rate) operating along the leaf economic spectrum. Observed mean LAI and LAI seasonality across the soil moisture stress gradient maximised NCE, and were therefore consistent with optimality‐based predictions. Yet, the predictive power of an optimality‐based approach was limited due to the asymptotic response of simulated NCE to mean LAI and LAI seasonality. Leaf traits fundamentally shaped the C budget, determining simulated optimal LAI and total NCE. Long‐lived leaves with lower maximum photosynthetic capacity maximised simulated NCE under aseasonal high mean LAI, with the reverse found for short‐lived leaves and higher maximum photosynthetic capacity. The simulated leaf trait LAI trade‐offs were consistent with observed distributions. We suggest that a range of LAI strategies could be equally economically viable at local level, though we note several ecological limitations to this interpretation (e.g. between‐plant competition). In addition, we show how leaf trait trade‐offs enable divergence in canopy strategies. Our results also allow an assessment of the usefulness of optimality‐based approaches in simulating primary tropical forest functioning, evaluated against in situ data.
A five‐step risk management process for geriatric dental practice during SARS‐CoV‐2 pandemic
Authors: Sivaraman Karthik , Chopra Aditi , Narayana Aparna , Radhakrishnan Raghu A.
Published: September 2020

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an RNA virus that causes coronavirus infection (COVID‐19). COVID‐19 is a highly contagious disease transmitted through respiratory droplets, saliva and other contact routes. Within 10 months of its outbreak, SARS‐CoV‐2 has infected more than 23 million people around the world. Evidence suggests that older adults are the most vulnerable to infection and have an increased risk of mortality. Reduced immunity and underlying medical conditions make them risk‐prone and vulnerable to critical care. Older adults affected with the SARS‐CoV‐2 virus present with distinct clinical manifestations necessitating specific treatment needs and management protocols. While it is crucial to prevent the spread of novel coronavirus (2019‐nCoV), the role of oral healthcare workers in addressing the specific needs of ageing adult patients by adopting specific guidelines and appropriate infection control protocols is timely. This paper aims to develop specific guidelines and protocols for the dental management of geriatric patients during the COVID‐19 pandemic.
Effect of physical exercise and medication on enhancing cognitive function in older adults with vascular risk
Authors: Fung Ada Wai‐Tung
Published: September 2020

Aim

To examine the association of physical exercise (PE) and medication on cognitive function in older adults with vascular risk.

Methods

This was a cross‐sectional study of 478 non‐demented participants aged ≥60 years with vascular risk. Management strategy included PE (mind–body exercise and/or strenuous exercise), medication, PE combined with medication and no management at all. Participation of PE was determined by self‐reporting exercise engagement in the past year. Cognitive preservation was defined as a global composite z‐score that was equal to or above the age and educational adjusted mean of cognitively normal older adults. Binary logistic regression was carried out to examine the association between management strategy and cognitive preservation in each exercise modality adjusted by sociodemographic, physical, mental and genetic factors.

Results

An association was found in preserved cognitive function for those who managed their vascular risk through PE (OR 2.5, 95% CI 1.2–5.3, P = 0.015) and in combination with medication (OR 2.1, 95% CI 1.0–4.6, P = 0.05). A similar pattern was also found in each exercise subtype. A significant short‐term (OR 3.6, 95% CI 1.0–12.4, P = 0.042) to lifelong (OR 3.5, 95% CI 1.4–8.5, P = 0.006) cognitive benefit was found in MB exercise.

Conclusion

Medication alone may be insufficient to preserve cognitive function in older adults with vascular risk. In our sample, medication in combined with PE is found to have significant impact on cognitive improvement. Mind–body exercise might be better than strenuous exercise, as a more sustainable cognitive effect is observed. Geriatr Gerontol Int 2020; 20: 1067–1071..
Making Black Lives Matter in academia: A Black feminist call for collective action against anti‐blackness in the academy
Authors: Bell Myrtle P. , Berry Daphne , Leopold Joy , Nkomo Stella
Published: September 2020

In this article, as have many Black women scholars in the past, we again call for collective action against anti‐blackness and White supremacy in the academy. Drawing from black feminist theory, we discuss the long history of Black women academics' activism against anti‐black racism and introduce the current movement: Black Lives Matter (BLM). Although BLM is often construed as resisting anti‐black violence outside the academy, it is also relevant for within the academy wherein anti‐blackness is likely to be manifested as disdain, disregard, and disgust for Black faculty and students. We discuss some of the ways in which anti‐blackness and liberal White supremacy are manifested in the lives of Black faculty and students, and propose that non‐Black allies have key roles to play in resisting them. Like second‐hand cigarette smoke that harms everyone in proximity, anti‐blackness and White supremacy harm us all, and a shared movement is needed to dismantle them.
What life in favelas can teach us about the COVID‐19 pandemic and beyond: Lessons from Dona Josefa
Authors: Quental Camilla , Shymko Yuliya
Published: September 2020

In this article, we adopt a non‐conventional approach to investigate the experiences and existential postures of women who, as residents of Brazilian favelas, find themselves at the frontline of a struggle for survival—and dignity—amid the COVID‐19 pandemic. We reveal this struggle through the voice of Dona Josefa—a 66‐year‐old, former domestic care worker and resident of Ocupação Esperança (Occupation Hope), a feminist favela on the outskirts of São Paulo. We interweave our reflections with those of Dona Josefa, who acts as representative of one of the many disenfranchised communities that are confronting one of the worst crises in recent history, in one of the most inequitable countries in the world. Connecting our discussion with feminist writers and calling attention to a more collective stance in feminism, overall, we offer a shift from knowledge gleaned from institutional and privileged spaces in the Global North to knowledge gained by observing individual struggles in the favelas of the Global South.
On the Performance of Pilot‐Point Based Hydraulic Tomography with a Geophysical a Priori Model
Authors: Poduri Sarada , Kambhammettu B.V.N.P.
Published: September 2020

We present a novel method to estimate the hydraulic and storage properties of a heterogeneous aquifer system using pilot‐point‐based hydraulic tomography (HT) inversion in conjunction with a geophysical a priori model. The a priori model involved a soil stratification obtained by combining electrical resistivity tomography inversion and field data from hydrogeological experiments. Pilot‐point densities were assigned according to the stratification, which also constrained aquifer parameters during HT inversion. The forward groundwater flow model, HydroGeoSphere, was supplied to the parameter‐estimation tool, PEST, to perform HT inversion. The performance of our method was evaluated on a hypothetical, two‐dimensional, multi‐layered, granitic aquifer system representative of those commonly occurring in the Kandi region in Telangana. Inversion results were compared using two commonly adopted methods of modeling parameter‐heterogeneity: (1) using piece‐wise zones of property values obtained from geostatistical interpolation of local‐scale estimates; and (2) HT inversion starting from a homogeneous parameter field with a uniform distribution of pilot‐points. Performances of the inverted models were evaluated by conducting independent pumping tests and statistical analyses (using a Taylor diagram) of the model‐to‐measurement discrepancies in drawdowns. Our results showed that using the aforementioned geophysical a priori model could improve the parameter‐estimation process.
Going Deep into Synaptic Vesicle Machinery Genes and Migraine Susceptibility – A Case‐Control Association Study
Authors: Quintas Marlene , Neto João Luís , Sequeiros Jorge , Sousa Alda , Pereira‐Monteiro José , Lemos Carolina , Alonso Isabel
Published: September 2020

Objective

A number of observations, including among our study population, have implicated variants in the syntaxin‐1A, a component of the synaptic vesicles, in migraine susceptibility. Therefore, we hypothesize that variants in other components of the vesicle machinery are involved in migraine.

Background

Migraine is a common and complex neurologic disorder that affects approximately 15‐18% of the general population. The exact cause of migraine is unknown; however, genetic studies have made possible substantial progress toward the identification of underlying molecular pathways. Neurotransmitters have been for long considered to have a key role in migraine pathophysiology; so we investigated common variants in genes involved in the synaptic vesicle machinery and their impact in migraine susceptibility.

Methods

We performed a case‐control study comprising 188 unrelated patients with headache and 286 healthy controls in a population from the north of Portugal. Benefiting from the presence of linkage disequilibrium, we selected and genotyped 119 tagging single‐nucleotide polymorphisms in 18 genes.

Results

We found significant associations between single‐nucleotide variants and migraine in 7 genes, SYN1, SYN2, SNAP25, VAMP2, STXBP1, STXBP5, and UNC13A, either conferring an increased risk or protection of migraine. Due to SYN1 X‐chromosomal location, we performed the statistical analysis separated by gender and, in the female group, the C allele of rs5906435 increased the risk for migraine susceptibility (P = .021; OR = 1.69; 95% CI: 1.21‐2.34). In contrast, the TT genotype of the same variant emerged as a potential protective factor (P = .003; OR = 0.45; 95% CI: 0.27‐0.74). The SYN2 analysis supported the rs3773364's G allele (P = .014) as a risk factor for migraine, and although not statistically significant after correction, the AG genotype (P = .006; OR = 1.86; 95% CI: 1.20‐2.90) reinforced the allelic findings. Additionally, we found the SNAP25‐rs363039's CT genotype (P = .001; OR = 2.14; 95% CI: 1.36‐3.34), the STXBP5‐rs1765028's T allele (P = .041; OR = 1.46; 95% CI: 1.13‐1.90), and the UNC13B‐rs7851161's TT genotype (P = .001; OR = 2.14; 95% CI: 1.36‐3.34) as statistically significant risk factors for migraine liability. VAMP2‐rs1150's G allele revealed a risk association to migraine, not statistically significant after correction (P = .068). Additionally, we found haplotypes in SYN1, SYN2, STXBP1, and UNC13B to be associated with migraine.

Conclusions

Overall, this study provides a new insight into migraine liability, identifying possible starting points for functional studies.
Reimagining Headache Fellowships
Authors: Zhang Niushen , Chan Tommy Lik Hang , Cowan Robert
Published: September 2020

In March of 2020, the COVID‐19 pandemic led to drastic changes in clinical practice and teaching methods. This article relates the experience of developing an almost virtual headache fellowship in response to the pandemic.
Intravenous Chlorpromazine as Potentially Useful Treatment for Chronic Headache Disorders
Authors: Ruiz Yanzi Maria A. , Goicochea Maria T. , Yorio Florencia , Alessandro Lucas , Farez Mauricio F. , Marrodan Mariano
Published: September 2020

Objective

The aim of this study was to describe a group of patients with chronic headache disorders (CH) and medication overuse headache (MOH) treated with intravenous chlorpromazine (IVC). We hypothesized that IVC is an effective and safe addition to well‐known treatment strategies for CH and MOH management.

Introduction

Up to 4% of the general population could experience CH. Most cases occur in women, in association with MOH. To date, evidence to support different treatment strategies is lacking. Although IVC is frequently used in the emergency room (ER), documentation on its use as supportive treatment for CH and for withdrawal management of MOH is poor.

Methods

A retrospective cohort of patients hospitalized to receive treatment for CH in a specialized neurological center in Argentina was analyzed.

Results

A total of 35 CH patients were included. Of the 35 patients, 33 (94%) patients also presented MOH. Patients reported only minor side effects to IVC administration (mainly drowsiness and symptomatic hypotension). Three months after inpatient treatment, the number of ER visits made by these patients decreased from an average of 2.8 in the 3 months prior to hospitalization to 0.7 after it (72%, P = .009). Headache frequency decreased in 20/34 (59%) patients during the same time period. Pain levels had dropped from a mean of 8 points at admission (in the scale of 1‐10) to 2 points at discharge. In the first 3 months of follow‐up, the average number of days per month in which patients experienced headache decreased from 28.9 to 15.4 days (53.3%, P < .0001).

Conclusion

In this particular group of inpatients, there were no significant safety issues with IVC administration and the study might suggest that the efficacy of IVC as an add‐on treatment for CH and MOH.
Case of hepatitis B virus reactivation after ibrutinib therapy in which the patient remained negative for hepatitis B surface antigens throughout the clinical course
Authors: Tsuruya Kota , Anzai Kazuya , Shioyama Shunsuke , Ito Ayano , Arase Yoshitaka , Hirose Shunji , Tanaka Yasuhito , Suzuki Hidekazu , Kagawa Tatehiro
Published: September 2020

A 71‐year‐old man was diagnosed with B‐cell chronic lymphocytic leukemia. He was negative for hepatitis B surface antigen (HBsAg), positive for antibodies against the hepatitis B surface and core, and negative for hepatitis B virus (HBV)‐DNA before starting chemotherapy. A total of 13 months after the initiation of ibrutinib (a Bruton's tyrosine kinase inhibitor), the patient's alanine aminotransferase levels suddenly increased to 427 U/L. As the level of serum HBV‐DNA increased to 5.2 logIU/mL, a diagnosis of HBV reactivation was made, whereas the patient remained negative for HBsAg. The patient's serum alanine aminotransferase levels normalized after the initiation of entecavir at a dose of 1 mg/day. However, it took >1 year to achieve an undetectable level of HBV‐DNA, even with an add‐on therapy of tenofovir disoproxil fumarate. Interestingly, the patient remained negative for HBsAg throughout the clinical course owing to triple HBsAg escape mutations: Q101K, M133L, and G145A.
Lessons learned from histological step‐sectioning of sentinel lymph nodes in penile cancer
Authors: Elversang Johanna , Grønkær Toft Birgitte , Predbjørn Krarup Kim , Jakobsen Jakob K
Published: September 2020

Aims

Histopathological examination of sentinel lymph nodes in penile cancer has varied during the first 10 years after introduction of the dynamic sentinel node (SLN) procedure in Denmark, and guidelines have been sparse. The aim of this study was to investigate the impact of rigorous step‐sectioning of sentinel lymph nodes in penile cancer and improve guidelines.

Methods and results

Seventy‐two penile squamous cell carcinoma patients undergoing SLN procedure at a single institution in 2000–2010 were included. The archived lymph node tissues already subjected to a standard pathological examination were retrieved and the initially negative lymph nodes were subjected to an extended step‐sectioning procedure. The results were compared to clinical patient outcome from a national database and subsequent pathology reports. The original histopathological examination had detected 26 SLN with metastasis, 21 macro metastases and five micro metastases. The additional step‐sectioning procedure of this study generated 4606 slides; seven SLN metastases, two macro metastases and five micro metastases, were detected. One of the macro metastases originated from a patient in which a clinical relapse had occurred in the same groin. None of the other metastases detected in this study showed ipsilateral relapse during follow‐up.

Conclusion

The results underline the value of our current practice of step‐sectioning sentinel lymph nodes in penile cancer and the need for histopathological routines and guidelines. The Danish national guidelines on histopathological handling of sentinel lymph nodes have been adapted to detect any potential clinically relevant metastases.