bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR/Cas12a‐mediated genome engineering in the photosynthetic bacterium Rhodobacter capsulatus
Authors: Zhang Yang , Yuan Jifeng
Published: March 2021

Purple non‐sulfur photosynthetic bacteria (PNSB) such as Rhodobacter capsulatus serve as a versatile platform for fundamental studies and various biotechnological applications. In this study, we sought to develop the class II RNA‐guided CRISPR/Cas12a system from Francisella novicida for genome editing and transcriptional regulation in R. capsulatus. Template‐free disruption method mediated by CRISPR/Cas12a reached ˜ 90% editing efficiency when targeting ccoO or nifH gene. When both genes were simultaneously edited, the multiplex editing efficiency reached > 63%. In addition, CRISPR interference (CRISPRi) using deactivated Cas12a was also evaluated using reporter genes egfp and lacZ, and the transcriptional repression efficiency reached ˜ 80%. In summary, our work represents the first report to develop CRISPR/Cas12a‐mediated genome editing and transcriptional regulation in R. capsulatus, which would greatly accelerate PNSB‐related researches.
Do Financing Constraints Lead to Incremental Tax Planning? Evidence from the Pension Protection Act of 2006*
Authors: Campbell John L. , Goldman Nathan C. , Li Bin
Published: March 2021

Over the past three decades, academic research has sought to understand how cash shortfalls impact a firm's ability to take all available value‐increasing investment projects. We investigate whether firms facing greater financing constraints turn to tax strategies that generate lower cash effective tax rates (ETRs) to mitigate the adverse effect of these financing constraints. We use the Pension Protection Act of 2006 (PPA 2006) as an exogenous shock to financing constraints for pension firms, but not for other firms. Using a difference‐in‐differences research design, we predict and find that pension firms experience a decrease in their cash ETRs by 1.8%–2.4% after the PPA 2006, relative to other firms. These cash tax savings mitigate the investment shortfall brought about by financing constraints by 19%. We also predict and find that the decline in cash ETRs is greater among firms more adversely affected by the PPA 2006. Our paper sheds light on the direction, causality, and economic magnitude of the association between financing constraints and tax planning activities. We also provide insight into the role of tax planning activities within firms' broader corporate business strategies in responding to financing constraints.
From ‘ovoid jars’ to ‘torpedo jars’: Investigations into bitumen‐lined transport containers in the Gulf and the Indian Ocean in antiquity (second century BCE–third century CE)
Authors: Durand Caroline
Published: March 2021

Research into bitumen‐lined ‘torpedo jars’, widely distributed throughout the Gulf and the Indian Ocean between the third and ninth centuries CE, has developed considerably in recent years, shedding new light on maritime trade connections during the Sasanian and early Islamic periods. Based on pottery finds from Failaka (Kuwait) and Thaj (Saudi Arabia), recently studied by the author, this article draws attention to an earlier type of bitumen‐lined jar characterised by an ovoid profile and a greenish fabric, including vegetal temper. These ovoid jars, presumably of Mesopotamian origin, are commonly found on ‘Classical’/pre‐Sasanian sites located along the Gulf’s shores, and their specific fabric has also been identified recently in Oman and southern India. They provide evidence for the existence of extensive Mesopotamian trade, probably in wine, with the Gulf region and more broadly with the Indian Ocean during the late Seleucid and Characenian periods.
Late Islamic water collection systems on Failaka Island: Preliminary results of the Kuwait–Georgian Archaeological Mission in 2018–2019
Authors: Chkhvimiani Jimsher , Mamiashvili Vazha , Bakhtadze Nodar , Kvavadze Eliso
Published: March 2021

Archaeological investigations on Failaka Island, conducted by the Kuwait–Georgian Archeological Mission, have recorded a variety of sites dating from different time periods, from the Bronze Age to the late Islamic/modern period. The largest proportion of recorded sites consist of late Islamic seasonal settlement structures found in the north‐eastern part of the island. It is possible that they were connected to fishing and associated activities such as stock‐farming and agriculture, which is confirmed by the results of palynological analysis. These sites are divided into two chronological phases: one from the seventeenth to eighteenth century and the second from the nineteenth to the first half of the twentieth century. In 2018, excavations at the water collection systems within these settlements began. The results gathered so far indicate that there were two kinds of well structures. The first are interpreted as shallow filtration well pits; the second are deep wells used for collecting water from deep underground. Both systems were used to collect rainwater, which was then filtered and stored. Marine and freshwater forms of algae were found in the basal sediments of the pits, which offers evidence for the accumulation and filtration of water.
Flow‐driven risk shifting of high‐performing funds
Authors: Jin Xuejun , Shen Yifan , Yu Bin , Qian Meifen
Published: March 2021

Using a sample of open‐end equity mutual funds in China from 2004 to 2017, this study investigates the motivations and consequences of flow‐driven fund risk shifting behaviour. We find that funds experiencing large inflows tend to reduce their degree of risk‐taking. However, good past performance drives funds with high net flows to increase their risk level. High‐performing funds increase risk by increasing turnover, increasing the proportion of equity holdings, and buying more winner stocks. Moreover, risk shifting caused by the flow‐driven trades of high‐performing funds worsens fund performance in the ensuing two quarters before recovering in the third quarter. Finally, high abnormal flow, high performance sourced from luck, young fund age, and small fund size enhance the risk shifting of high‐performing funds when experiencing high flow.
Thousands of bats: A portrait of the chiropteran fauna of Palmas city, Central Brazil
Authors: Benvindo‐Souza Marcelino , de Souza Santos Lia Raquel , Elias Borges Rinneu , Alves de Assis Rhayane , de Melo e Silva Daniela , Zortéa Marlon , Missel Pacheco Susi
Published: March 2021

Urban development remodels the natural landscape and reconfigures local faunal communities. This study investigated for the first time the composition of bats in the city of Palmas, a rapidly growing urban centre in the state of Tocantins, Brazil. We recorded twenty‐three species of bats, most of them frugivorous, and we try to launch light on a large colony of urban insectivorous bats. This bat colony contained an estimated one million broad‐eared bats (Nyctinomops laticaudatus), and resided under the Fernando Henrique Cardoso Bridge of Friendship and National Integration, over the Tocantins River, between April and the beginning of October. This site has been certified as a Site of Special Importance for Bat Conservation by the Latin American and Caribbean Bat Conservation Network. The protection of the city’s bats in general, and the bridge colony, in particular, will depend on efforts to raise the awareness of state and municipal authorities, programmes of environmental education and even the exploitation of the potential for local tourism.
The distribution and immunolocalization of fibroblast growth factors (FGFs) in the rat oviduct during early pregnancy and the post‐partum period
Authors: Alan Emel , Liman Narin
Published: March 2021

The mammalian oviduct provides a favourable environment for several reproductive processes, including ovum transport, sperm capacitation, fertilization and pre‐implantation embryonic development. This environment is regulated by cyclic ovarian steroids, that is oestrogen, and growth factors. Fibroblast growth factors (FGFs) regulate the differentiation and growth of various cell types in the female genital tract. This study aimed to determine the localization of FGF1, FGF2, FGF receptor 1 (FGFR1) and 2 (FGFR2) in the rat oviduct, by immunohistochemistry, on day 5 of pregnancy and post‐partum days 1, 3 and 5, and to demonstrate the possible functions of these proteins during early pregnancy and the post‐partum period. On all examination days, cytoplasmic and nuclear FGF1 immunoreactivity was detected in the epithelium lining the infundibulum, ampulla and isthmus of the oviduct. Immunoreactivity was much stronger in the basal bodies of the cilia on the epithelium lining the infundibulum and ampulla. FGF1 immunoreactivity was also detected in stromal cells, myocytes and endothelial cells. Cytoplasmic FGF2 immunoreactivity was observed in the tunica muscularis, vascular myocytes and endothelial cells. While strong cytoplasmic FGF2 immunoreactions were observed in the stromal cells of the lamina propria, the luminal epithelium, some stromal cells and smooth muscle cells displayed a rather weak FGFR1 and FGFR2 immunoreactivity. Immunoreaction intensity did not differ between the periods examined. This study shows that FGF1, FGF2, FGFR1 and FGFR2 are produced by rat oviduct cells during pregnancy and the post‐partum period, and reproductive physiology is regulated not only by hormonal mechanisms, but also by growth factors.
Comparing the Rate of Nicotine Metabolism Among Smokers With Current or Past Major Depressive Disorder
Authors: Schnoll Robert , Paul Wileyto E. , Bauer Anna‐Marika , Fox Erica , Leone Frank , Lerman Caryn , Tyndale Rachel F. , George Tony P. , Hawk Larry , Cinciripini Paul , Quinn Mackenzie , Purnell Janelle , Hatzell Jane , Hitsman Brian
Published: March 2021

Background and Objectives

Persons with current or past major depressive disorder (MDD) vs those without have higher smoking rates. The nicotine metabolite ratio (NMR) represents variation in the rate of nicotine metabolism and has been associated with smoking behaviors and response to tobacco treatments. We compared NMR between smokers with current or past MDD (MDD+) vs smokers without MDD (MDD−). We also assessed correlates of NMR and compared withdrawal and craving between MDD+ and MDD− smokers.

Methods

Using baseline data from two clinical trials and propensity score weighting based on sex, race, body mass index, and smoking rate, we compared NMR between MDD+ (N = 279) and MDD− (N = 1575) smokers. We also compared groups on and nicotine withdrawal and craving.

Results

Mean NMR (β = −.02, 95% confidence interval [CI]: −0.05 to 0.01, P = .13) and the distribution of smokers across NMR quartiles (odds ratio [OR] = 0.76, 95% CI: 0.50 to 1.16, P = .21) were similar between MDD+ and MDD− samples. This relationship was not affected by antidepressant medication. In the MDD+ sample, African Americans had significantly lower mean NMR, while older smokers and smokers with lower education had higher mean NMR (Ps < .05). MDD+ smokers had significantly higher withdrawal and craving than MDD− smokers (Ps < .05).

Discussion and Conclusions

While variability in NMR may not explain differences in smoking rates between MDD+ and MDD− smokers, MDD+ smokers report increased withdrawal and craving.

Scientific Significance

In this first study to assess NMR among MDD+ smokers, the findings underscore the need to address withdrawal and craving within smoking cessation treatments for those with MDD. (Am J Addict 2021;00:00–00)
Unexplained recurrent miscarriages: predictive value of immune biomarkers and immunomodulatory therapies for live birth
Authors: Kolanska Kamila , Dabi Yohann , Dechartres Agnès , Cohen Jonathan , Ben Kraiem Yasmine , Selleret Lise , Mathieu d’Argent Emmanuelle , Placais Leo , Cheloufi Meryem , Johanet Catherine , Rosefort Audrey , Bornes Marie , Suner Ludovic , Delhommeau Francois , Ledée Nathalie , Chabbert Buffet Nathalie , Darai Emile , Antoine Jean Marie , Fain Olivier , Kayem Gilles , Mekinian Arsène
Published: March 2021

Introduction

Recurrent miscarriages are defined as three or more early miscarriages before 12 weeks of gestation. The aim of this study was to describe a cohort of women with unexplained recurrent miscarriages, evaluate several potential biomarkers of immune origin, and describe the outcome of pregnancies under immunomodulatory therapies.

Methods

Women having a history of at least 3 early miscarriages without any etiology were recruited from 3 university hospitals.

Results

Among 101 women with recurrent miscarriages, overall, 652 pregnancies have been included in the analysis. Women which experienced miscarriages were older (33.3 ± 5.4 versus 31.9 ± 6.7; p = 0.03), with history of more pregnancies (4 (2–6) versus 3.5 (1–5.75); p 0.0008), and less frequently the same partner (406 (74%) versus 79 (86%); p=0.01). There was no difference in the level and frequencies of biomarkers of immune origin (NK, lymphocyte, gamma globulins and blood cytokine levels and endometrial uNK activation status), except the higher rates of positive antinuclear antibodies in women with live birth (12 (13%) versus 36 (7%); p=0.03). Among the 652 pregnancies, 215 (33%) have been treated and received either aspirin/low weighted molecular heparin (LMWH) and/or combined to different lines of immunomodulatory treatment. Patients with pregnancy under treatment had a significantly higher rate of cumulative live birth rate than those with untreated ones (43.0% vs 34.8%; p = 0.04). When compared to patients with untreated pregnancies, patients with steroids during the pregnancy had twice more chances to obtain live birth (OR 2.0, CI95% 1.1 – 3.7, p = 0.02).

Conclusions

Unexplained recurrent miscarriages could have improved obstetrical outcome under immunomodulatory therapies and in particular steroids.
Defining competency for Royal Australian and New Zealand College of Obstetricians and Gynaecologists training: An exploratory study of Victorian Integrated Training Program coordinators’ understanding of competency
Authors: Pagram Heather , Bilszta Justin L.C. , Szabo Rebecca A.
Published: March 2021

Background

Competency‐based medical education (CBME) is increasingly employed by postgraduate training programs worldwide, including obstetrics and gynaecology. Focusing on assessment of outcomes rather than time‐in‐training, and utilising a well‐defined curricular framework, CBME aims to train doctors capable of meeting the needs of modern society. When this study was undertaken, in 2019, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) had a time‐based curriculum and was due to undergo a curriculum review starting in 2020.

Aims

To explore Victorian RANZCOG Integrated Training Program (ITP) coordinators’ understanding of the concept of competency and how it is taught and assessed within RANZCOG training.

Materials and Methods

A qualitative, grounded theory design using semi‐structured interviews was employed. Victorian RANZCOG ITP coordinators from inner and outer metropolitan, and regional sites, were approached to participate. Transcripts were coded and analysed using thematic analysis.

Results

Themes identified were: Competence, Vision and Innovation, Structures, ITP Coordinator Role and Teaching and Learning. Competence was defined as a combination of independent practice and understanding of ones’ own limits, in addition to required clinical skills and knowledge. Enablers and barriers to achieving competency were identified and associated with structures, human and logistical factors. Victorian ITP coordinators believed the current training program has positive elements but could be further improved.

Conclusions

Several areas for future research were identified regarding understanding of competency, relevant if RANZCOG is to introduce a CBME framework. Replicating this research across all RANZCOG jurisdictions in Australia and New Zealand would be prudent to determine if the themes are universal.
Evaluation of the potential role of shear wave elastography as a promising predictor of sperm retrieval in non‐obstructive azoospermic patients: A prospective study
Authors: Abdelaal Alaaeldien Mohamed Abdelmoniem , El‐Azizi Hatem Mohamed , GamalEl Din Sameh Fayek , Abdulsalam Mohammad Azzazi Omar , Shokr Mohamed Mohamed
Published: March 2021

Background and Objectives

Testicular sperm extraction (TESE) has been a useful diagnostic and therapeutic tool with sperm retrieval opportunity varying according to the pathological finding in azoospermic patients. Sonoelastography (SE) is an exciting radiologic method that can measure relative elasticity of different tissues in a selected region of interest (ROI) by depending on fast cross‐correlation technique and a combined autocorrelation method. Real‐time elastography (RTE) can be used for structural analysis of testicular tissue to detect pathological tissue alterations. We aimed in the current study to evaluate the efficacy of shear wave elastography (SWE) in predicting sperm retrieval in non‐obstructive azoospermic (NOA) patients undergoing TESE.

Patients and methods

This prospective study included 50 NOA patients who did two successive semen analyses with normal or elevated gonadotrophic hormones. All participants were subjected to SWE imaging on the testes by a radiologist. The measurements were recorded in terms of kPa using the SWE mode. They were done on each testis in the longest longitudinal plane. SWE images were viewed using dual mode: elasticity mode (kPa) and propagation (arrival time contour) mode then patients underwent TESE.

Results

A significant difference in SWE values was observed between patients with successful sperm retrieval and those with negative sperm retrieval providing 94.7% negative predictive value and 50.0% positive predictive value for sperm retrieval in NOA patients undergoing TESE with 75.0% sensitivity and 85.71% specificity (p  =  0.0001). Mean stiffness index measured by SWE correlated significantly with the histopathological types as 8 patients only were diagnosed as having severe hypospermatogenesis.

Discussion and Conclusion

These prime data suggest that SWE as a non‐invasive, easily applicable, and repeatable imaging method has a promising potential to be one of the reliable sonographic modalities that can be used as one of the predictors for sperm retrieval in NOA patients.
Computer‐delivered behavioural activation and approach‐avoidance training in major depression: Proof of concept and initial outcomes
Authors: Sweet Alison M. , Pearlstein Sarah L. , Paulus Martin P. , Stein Murray B. , Taylor Charles T.
Published: March 2021

Objectives

Individuals with major depressive disorder (MDD) have problems with engaging in approach behaviour to potentially rewarding encounters, which contributes to the maintenance of depressive symptoms. Approach‐avoidance training (AAT) retrains implicit approach tendencies, and behavioural activation (BA) promotes explicit approach behaviour in MDD. As a novel MDD treatment strategy, this study aimed to implement a brief, computerized version of BA integrated with implicit AAT.

Design

Adults with a principal diagnosis of MDD (N = 25) were randomly assigned to complete one of two versions of AAT – approach‐positive faces (n = 12) or balanced approach of positive and neutral faces (n = 13) – concurrently with self‐guided BA twice weekly for 2 weeks.

Methods

Outcomes included treatment completion rates; bias scores for automatic approach towards positive social cues; and symptom scales for depression, positive affect, social relationship functioning, anhedonia, and anxiety.

Results

Feasibility and acceptability of computerized BA + AAT were supported by moderate pre‐treatment credibility and expectancy ratings and 80% treatment completion. Participants across both conditions displayed significant and large sized reductions in depression from pre‐ to post‐assessment (Cohen’s d = −1.23) that maintained three months later, as well as decreased anxiety and anhedonia and increased positive affect and social relationship functioning (medium to large effects).

Conclusion

Results support the feasibility and potential efficacy of brief, computerized BA + AAT. Research is needed to determine whether AAT is additive to BA, and what AAT parameters best enhance treatment outcomes.

Practitioner Points

Brief, computerized behavioral activation plus approach/avoidance training (BA + AAT) may be acceptable and beneficial for some patients with moderate‐to‐severe major depression.

Computer‐delivered BA + AAT can be implemented as a largely self‐guided program for MDD and could be administered remotely and/or with minimal clinician interaction.

As this was a small proof of concept study, it cannot be determined which treatment components – AAT, BA, or both – contributed to positive clinical outcomes.

Because BA + AAT was implemented in a research clinic, it remains unknown what treatment engagement and response would look like in community settings.
Urological litigation trends in the UK National Health Service: an analysis of claims over 20 years
Authors: Lane Jenni , Bhome Rahul , Somani Bhaskar
Published: March 2021

Objective

To look into the urology litigation trends and successful claims in the National Health Service (NHS) over the last 20 years.

Methods

We requested data from NHS Resolutions to investigate current litigation numbers, costs and causes for claims. Data collected included the number of claims dating from 1996 to 2019, the total sum of damages paid out each year for urology and the causes for the claims dating from 2009 to 2019. Data from NHS Resolutions were analysed, stratified and categorized by the authors from this information, which was provided as two separate documents.

Results

The total cost of damages between 1997 and 2017 was £74.5m (range: £241 325–£7.8m per year). While the number of successful claims was 1653 (range 7–168 per year), the total number of claims was 3341 (range 31–347 per year) and, over time, this has increased almost sevenfold. The cost of damages has increased roughly in line with the number of claims. Over the last 10 years, non‐operative‐related claims accounted for 984 claims, of which the largest subset was for ‘the failure to diagnose and/or treat’ (n = 639, 65%), with 88 (9%) successful consent‐related claims. There were 226 intra‐operative‐related claims. Of these, wrong‐site surgery, a never‐event, accounted for eight claims and there were six successful claims for failing to supervise juniors. A total of 1129 claims were postoperative claims, with retained foreign body or instrument accounting for 71 (6%) of these.

Conclusions

The number and cost of litigation claims have increased year on year. There is a need for continual improvement in patient care, surgical training, counselling, informed consent and early management of complications. The evidence reviewed in this paper suggests that the best approach to this is the combination of rigid adherence to and re‐enforcement of common surgical guidelines and implementation of the national ‘Getting it right first time’ initiative.
Proposing a model for promoting Children's Health in Early Childhood Education and Care Settings
Authors: Musgrave Jackie , Payler Jane
Published: March 2021

This pilot study was conducted in one early childhood pre‐school nursery setting in an area of high deprivation in England to explore the under‐researched area of how practitioners promote the health of children. The research used an original tool, Child Health Promotion: A Toolkit for Early Childhood Education and Care Practitioners, containing a 5 Step Programme as a model to guide practitioners in identifying and implementing a health promotion activity. The findings will help to set the onward agenda for a larger scale study which will foreground the voices of practitioners and highlight the role that ECEC practitioners can play in promoting the health of children.
Investigation of risk factors associated with erythrocyte engraftment after ABO‐incompatible hematopoietic stem cell transplantation
Authors: Yanagisawa Ryu , Nakazawa Hideyuki , Nishina Sayaka , Saito Shoji , Shigemura Tomonari , Tanaka Miyuki , Nakazawa Yozo
Published: March 2021

ABO‐incompatible hematopoietic stem cell transplantations (HSCTs) are widely practiced; however, the delay in erythrocyte engraftment can be problematic. While erythrocyte engraftment is usually indicated by an increase in reticulocyte levels without the need for erythrocyte transfusions, the disappearance of recipient‐derived anti‐A/B isoagglutinin and detection of donor‐derived A/B antigens can also be used as other parameters. We conducted a retrospective analysis of 68 ABO‐incompatible HSCTs, focusing on major and bidirectional mismatch. We analyzed known clinical risk factors associated with delayed erythrocyte engraftment using the three parameters (disappearance of anti‐A/B isoagglutinin in recipient, detection of donor‐derived A/B antigen, and reticulocyte levels >1%). Although the three parameters were well correlated, the results showed heterogeneity when analyzing the associated risk factors for delayed erythrocyte engraftment. In the analysis of all cases, the requirement for an HLA‐matched platelet transfusion was a common risk factor. Furthermore, erythrocyte engraftment was slower in adults than in children. In adults, cytomegalovirus antigenemia was a risk factor for two parameters; however, in children, underlying disease was a common risk factor for all parameters. There is a complex relationship between erythrocyte engraftment and various factors related to HSCTs. Our results suggest that greater accuracy is possible by using analysis methods other than the measurement of reticulocyte levels.
The role of advanced endoscopy in the management of inflammatory digestive diseases (upper gastrointestinal tract)
Authors: Nagahara Akihito , Shiotani Akiko , Iijima Katsunori , Kamada Tomoari , Fujiwara Yasuhiro , Kasugai Kunio , Kato Mototsugu , Higuchi Kazuhide
Published: March 2021

The Japan Gastroenterological Endoscopy Society held four serial symposia between 2019 and 2020 on the state‐of‐the‐art of issues related to upper GI inflammatory diseases. This review discusses some of the topics addressed in these symposia. The papers regarding nonerosive reflux disease, recent improvements in intraesophageal pH‐impedance monitoring and endoscopic diagnosis using image‐enhanced endoscopy have been published. Many publications have addressed its usefulness in endoscopic treatment of gastroesophageal reflux disease such as anti‐reflux mucosectomy. In the management of eosinophilic esophagitis, since the symptoms are subjective, objective indicators have been sought, and ultrasonography and high‐resolution manometry may be useful tools for evaluation. The natural course of this condition, especially of asymptomatic cases, is not well clarified. Some newly developed anti‐acid or anti‐inflammatory medicines are now under investigation. With regard to autoimmune gastritis, because of widespread medical examinations, diagnosis of asymptomatic cases has been increasing. Recently, its endoscopic characteristics have become clear and the natural history of these conditions is being elucidated. The Kyoto Classification of Gastritis has been reported to be useful not only for Helicobacter pylori diagnosis but also for identification of risks of gastric cancer. Its usefulness is now recognized in Asia and Europe.
Pharmacological and neurosurgical interventions for individuals with cerebral palsy and dystonia: a systematic review update and meta‐analysis
Authors: Bohn Emma , Goren Katherine , Switzer Lauren , Falck‐Ytter Yngve , Fehlings Darcy
Published: March 2021

Aim

To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and dystonia.

Method

Searches were updated (January 2016 to May 2020) for oral baclofen, trihexyphenidyl, benzodiazepines, clonidine, gabapentin, levodopa, botulinum neurotoxin (BoNT), intrathecal baclofen (ITB), and deep brain stimulation (DBS), and from database inception for medical cannabis. Eligible studies included at least five individuals with CP and dystonia and reported on dystonia, goal achievement, motor function, pain/comfort, ease of caregiving, quality of life (QoL), or adverse events. Evidence certainty was evaluated using GRADE.

Results

Nineteen new studies met inclusion criteria (two trihexyphenidyl, one clonidine, two BoNT, nine ITB, six DBS), giving a total of 46 studies (four randomized, 42 non‐randomized) comprising 915 participants when combined with those from the original systematic review. Very low certainty evidence supported improved dystonia (clonidine, ITB, DBS) and goal achievement (clonidine, BoNT, ITB, DBS). Low to very low certainty evidence supported improved motor function (DBS), pain/comfort (clonidine, BoNT, ITB, DBS), ease of caregiving (clonidine, BoNT, ITB), and QoL (ITB, DBS). Trihexyphenidyl, clonidine, BoNT, ITB, and DBS may increase adverse events. No studies were identified for benzodiazepines, gabapentin, oral baclofen, and medical cannabis.

Interpretation

Evidence evaluating the use of pharmacological and neurosurgical management options for individuals with CP and dystonia is limited to between low and very low certainty.

What this paper adds

Meta‐analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain.

Meta‐analysis suggests that DBS may improve motor function.

Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals.

ITB and DBS may improve quality of life.

No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis.
Living with diabetes alongside a severe mental illness: A qualitative exploration with people with severe mental illness, family members and healthcare staff
Authors: Bellass Sue , Lister Jennie , Kitchen Charlotte Emma Wray , Kramer Lyndsey , Alderson Sarah Louise , Doran Tim , Gilbody Simon , Han Lu , Hewitt Catherine , Holt Richard Ian Gregory , Jacobs Rowena , Prady Stephanie Louise , Shiers David , Siddiqi Najma , Taylor Johanna
Published: March 2021

Aims

Diabetes is two to three times more prevalent in people with severe mental illness, yet little is known about the challenges of managing both conditions from the perspectives of people living with the co‐morbidity, their family members or healthcare staff. Our aim was to understand these challenges and to explore the circumstances that influence access to and receipt of diabetes care for people with severe mental illness.

Methods

Framework analysis of qualitative semi‐structured interviews with people with severe mental illness and diabetes, family members, and staff from UK primary care, mental health and diabetes services, selected using a maximum variation sampling strategy between April and December 2018.

Results

In all, 39 adults with severe mental illness and diabetes (3 with type 1 diabetes and 36 with type 2 diabetes), nine family members and 30 healthcare staff participated. Five themes were identified: (a) Severe mental illness governs everyday life including diabetes management; (b) mood influences capacity and motivation for diabetes self‐management; (c) cumulative burden of managing multiple physical conditions; (d) interacting conditions and overlapping symptoms and (e) support for everyday challenges. People living with the co‐morbidity and their family members emphasised the importance of receiving support for the everyday challenges that impact diabetes management, and identified barriers to accessing this from healthcare providers.

Conclusions

More intensive support for diabetes management is needed when people's severe mental illness (including symptoms of depression) or physical health deteriorates. Interventions that help people, including healthcare staff, distinguish between symptoms of diabetes and severe mental illness are also needed.
‘I was ready for it at the beginning’: Parent experiences with early introduction of continuous glucose monitoring following their child's Type 1 diabetes diagnosis
Authors: Tanenbaum Molly L. , Zaharieva Dessi P. , Addala Ananta , Ngo Jessica , Prahalad Priya , Leverenz Brianna , New Christin , Maahs David M. , Hood Korey K.
Published: March 2021

Aim

This study aimed to capture the experience of parents of youth with recent onset Type 1 diabetes who initiated use of continuous glucose monitoring (CGM) technology soon after diagnosis, which is a new practice.

Methods

Focus groups and individual interviews were conducted with parents of youth with Type 1 diabetes who had early initiation of CGM as part of a new clinical protocol. Interviewers used a semi‐structured interview guide to elicit feedback and experiences with starting CGM within 30 days of diagnosis, and the benefits and barriers they experienced when adjusting to this technology. Groups and interviews were audio recorded, transcribed and analysed using content analysis.

Results

Participants were 16 parents (age 44.13 ± 8.43 years; 75% female; 56.25% non‐Hispanic White) of youth (age 12.38 ± 4.15 years; 50% female; 50% non‐Hispanic White; diabetes duration 10.35 ± 3.89 months) who initiated CGM 11.31 ± 7.33 days after diabetes diagnosis. Overall, parents reported high levels of satisfaction with starting CGM within a month of diagnosis and described a high level of reliance on the technology to help manage their child's diabetes. All participants recommended early CGM initiation for future families and were committed to continue using the technology for the foreseeable future, provided that insurance covered it.

Conclusion

Parents experienced CGM initiation shortly after their child's Type 1 diabetes diagnosis as a highly beneficial and essential part of adjusting to living with diabetes.
Mortality in 98 type 1 diabetes mellitus and type 2 diabetes mellitus: Foot ulcer location is an independent risk determinant
Authors: Schofield Heather , Haycocks Samantha , Robinson Adam , Edmonds Michael , Anderson Simon G , Heald Adrian H.
Published: March 2021

Introduction

We previously demonstrated in both a longitudinal study and in meta‐analysis (pooled relative‐risk RR, 2.45) that all‐cause mortality is significantly higher in people with diabetes foot ulceration (DFU) than with those without a foot ulcer. In this prospective study, we looked at the factors linked to mortality after presentation to podiatry with DFU.

Methods

Ninety‐eight individuals recruited consecutively from the Salford Royal Hospital Multidisciplinary Foot Clinic in Spring 2016 were followed up for up to 48 months. Data concerning health outcomes were extracted from the electronic patient record (EPR).

Results

Seventeen people (17) had type 1 diabetes mellitus, and 81 had type 2 diabetes mellitus. Thirty‐one were women. The mean age (range) was 63.6 (28–90) years with maximum diabetes duration 45 years. Mean HbA1c was 72 (95% CI: 67–77) mmol/mol; 97% had neuropathy (International Working Group on the Diabetic Foot (IWGDF) monofilament); 62% had vascular insufficiency (Doppler studies); 69% of ulcers were forefoot, and 23% of ulcers were hind foot in location.

Forty of 98 (40%) patients died in follow‐up with 27% of death certificates including sepsis (not foot‐related) and 35% renal failure as cause of death. Multivariate regression analysis indicated a 6.3 (95% CI: 3.9–8.1) fold increased risk of death with hind foot ulcer, independent of age/BMI/gender/HbA1c/eGFR/total cholesterol level.

Conclusion

This prospective study has indicated a very high long‐term mortality rate in individuals with DFU, greater for those with a hind foot ulcer and shown a close relation between risk of sepsis/renal failure and DFU mortality, highlighting again the importance of addressing all risk factors as soon as people present with a foot ulcer.
The relationship between calcific severe aortic stenosis and systemic immune‐inflammation index
Authors: Erdoğan Mehmet , Öztürk Selçuk , Kardeşler Burak , Yiğitbaşı Murat , Kasapkara Hacı Ahmet , Baştuğ Serdal , Erdöl Mehmet Akif , Akar Bayram Nihal , Akçay Murat , Durmaz Tahir
Published: March 2021

Aim

Calcific aortic stenosis (AS) is a common valvular disease especially in elderly population. Inflammation plays significant role in the pathophysiological mechanism. Systemic immune‐inflammation index (SII) is a novel marker of immune system and inflammation that includes neutrophil, lymphocyte, and platelet cell counts. The aim of this study was to investigate the predictive value of SII in calcific severe AS.

Materials and Methods

Severe calcific AS patients were categorized into two groups: High flow‐high gradient (HFHG) AS (n = 289) and low flow‐low gradient AS (n = 79). Control group included 273 patients with similar clinical and demographic characteristics but without AS. SII was calculated as absolute platelet count × absolute neutrophil count/absolute lymphocyte count.

Results

SII levels were 525 ± 188, 835 ± 402, and 784 ± 348 in control, HFHG AS, and LFLG AS groups, respectively (P < .001). Correlation analyses revealed significant and positive correlation between SII and mean aortic transvalvular pressure gradient (r = .342, P < .001), and negative and significant correlation between SII and AVA (r = −.461, P < .001). Multivariate analysis performed in separate models demonstrated sex, CAD, LDL, and SII levels (Odds ratio [OR]: 1.004, 95 CI%:1.003–1.004) as independent predictors of severe AS in Model 1. According to Model 2, sex, CAD, LDL, and high SII (>661) (OR:5.78, 95 CI%:3.93–4.89) remained as independent predictors of severe AS.

Conclusion

SII levels can be useful to predict severe calcific AS patients and significantly correlate with AVA and mean aortic transvalvular pressure gradient.
COVID‐19 (SARS‐CoV‐2) infection and thrombotic conditions: A systematic review and meta‐analysis
Authors: Gabbai‐Armelin Paulo Roberto , de Oliveira Analú Barros , Ferrisse Túlio Morandin , Sales Luciana Solera , Barbosa Elis Rodrigues Oliveira , Miranda Marina Lins , Salomão Karina Borges , Brighenti Fernanda Lourenção
Published: March 2021

Background

COVID‐19 is an infectious disease caused by SARS‐CoV‐2 associated with haematological manifestations (thrombolytic events).

Aims

Considering the high prevalence of the thrombotic scenarios associated with COVID‐19, the aim of this study was to perform a systematic review of the available literature, concerning the relation of COVID‐19 and the thrombotic events, and identify prognostic factors for these events.

Materials & Methods

PubMed, Web of Science and Scopus databases were searched. Independent reviewers conducted all flow diagram steps. For qualitative analysis, Oxford level of evidence and Newcastle‐Ottawa scale were used in the eligible articles. For the prognostic factors, a meta‐analysis was conducted to age, number of neutrophils and platelets, and levels of ferritin, C‐reactive protein, lactate dehydrogenase and D‐dimer. Publication bias was accessed by funnel plot and by trim‐and‐fill test. Trim‐and‐fill test was also applied to evaluate meta‐analysis bias.

Results

Twenty articles were included in the qualitative analysis, and 6 articles were included in the meta‐analysis. Case‐control studies showed bias related to exposure, and the main bias in cohort studies were related to selection and outcome. All articles received score 4 for the level of evidence. Hypertension and diabetes were the comorbidities more frequently associated with thrombolytic events. Significant results were found regarding D‐dimer (P < .0001) and age (P = .0202) for thrombotic events in patients diagnosed with COVID‐19.

Conclusion

Patients older than 60 years, with hypertension, diabetes and D‐Dimer values above 3.17 µg/mL, can be considered prognostic factors for developing thrombotic events due to COVID‐19.
Point at, nudge, or push private provision of a public good?
Authors: Bruns Hendrik , Perino Grischa
Published: March 2021

How decision makers respond to behavioral and traditional interventions might depend on their and the regulator's attributes. This online experiment investigates the effect of defaults, recommendations, and mandatory minimum contributions accompanied by regulator information on the private provision of climate protection, accounting for intrinsic motivation. Findings show that all interventions increase the propensity of individuals to choose the focal value. There is no evidence that recommendations and defaults change average contributions. We report a negative interaction of the default with intrinsic motivation. Expert or political regulator information decreases intervention effectiveness. The study improves our understanding of behavioral public policy instruments.
The intervention of mechanical tactile stimulation modulates somatosensory evoked magnetic fields and cortical oscillations
Authors: Kojima Sho , Otsuru Naofumi , Miyaguchi Shota , Yokota Hirotake , Nagasaka Kazuaki , Saito Kei , Inukai Yasuto , Shirozu Hiroshi , Onishi Hideaki
Published: March 2021

The different cortical activity evoked by a mechanical tactile stimulus depends on tactile stimulus patterns, which demonstrates that simple stimuli (i.e., global synchronous stimulation the stimulus area) activate the primary somatosensory cortex alone, whereas complex stimuli (i.e., stimulation while moving in the stimulus area) activate not only the primary somatosensory cortex but also the primary motor area. Here, we investigated whether the effects of a repetitive mechanical tactile stimulation (MS) on somatosensory evoked magnetic fields (SEFs) and cortical oscillations depend on MS patterns. This single‐blinded study included 15 healthy participants. Two types interventions of MS lasting 20 min were used: a repetitive global tactile stimulation (RGS) was used to stimulate the finger by using 24 pins installed on a finger pad, whereas a sequential stepwise displacement tactile stimulation (SSDS) was used to stimulate the finger by moving a row of six pins between the left and right sides on the finger pad. Each parameter was measured pre‐ and post‐intervention. The P50m amplitude of the SEF was increased by RGS and decreased by SSDS. The modulation of P50m was correlated with its amplitude before RGS and with the modulation of beta band oscillation at the resting state after SSDS. This study showed that the effects of a 20‐min MS on SEFs and cortical oscillations depend on mechanical tactile stimulus patterns. Moreover, our results offer potential for the modulation of tactile functions and selection of stimulation patterns according to cortical states.
Long‐term zero‐tillage enhances the protection of soil carbon in tropical agriculture
Authors: Cooper Hannah V. , Sjögersten Sofie , Lark Richard M. , Girkin Nicholas T. , Vane Christopher H. , Calonego Juliano C. , Rosolem Ciro , Mooney Sacha J.
Published: March 2021

Contrasting tillage strategies not only affect the stability and formation of soil aggregates but also modify the concentration and thermostability of soil organic matter associated with soil aggregates. Understanding the thermostability and carbon retention ability of aggregates under different tillage systems is essential to ascertain potential terrestrial carbon storage. We characterized the concentration and thermostability of soil organic carbon (SOC) within various aggregate size classes under both zero and conventional tillage using novel Rock‐Eval pyrolysis. The nature of the pore systems was visualized and quantified by X‐ray computed tomography to link soil structure to organic carbon preservation and thermostability. Soil samples were collected from experimental fields in Botucatu, Brazil, which had been under zero‐tillage for 2, 15 and 31 years, and from adjacent fields under conventional tillage. Soils under zero‐tillage significantly increased pore connectivity whilst simultaneously decreasing interaggregate porosity, providing a potential physical mechanism for protection of SOC in the 0–20‐cm soil layer. Changes in the soil physical characteristics associated with the adoption of zero‐tillage resulted in improved aggregate formation compared to conventionally tilled soils, especially when implemented for at least 15 years. In addition, we identified a chemical change in composition of organic carbon to a more recalcitrant fraction following conversion to zero‐tillage, suggesting aggregates were accumulating rather than mineralizing SOC. These data reveal profound effects of different tillage systems upon soil structural modification, with important implications for the potential of zero‐tillage to increase carbon sequestration compared to conventional tillage.

Highlights

Different tillage systems may affect SOC thermostability and C retention potentials of soil aggregates.

SOC thermostability was characterised by Rock‐Eval pyrolysis and pore systems were quantified by X‐ray CT within aggregate size classes.

Profound effects of zero versus conventional tillage upon soil structural modification were observed

Important implications for zero‐tillage to increase C sequestration versus conventional tillage.
Thrombolytic therapy for wake‐up stroke: A systematic review and meta‐analysis
Authors: Mac Grory Brian , Saldanha Ian J. , Mistry Eva A. , Stretz Christoph , Poli Sven , Sykora Marek , Kellert Lars , Feil Katharina , Shah Shreyansh , McTaggart Ryan , Riebau Derek , Yaghi Shadi , Gaines Kenneth , Xian Ying , Feng Wuwei , Schrag Matthew
Published: March 2021

Background and purpose

According to evidence‐based clinical practice guidelines, patients presenting with disabling stroke symptoms should be treated with intravenous tissue plasminogen activator (IV tPA) within 4.5 h of time last known well. However, 25% of strokes are detected upon awakening (i.e., wake‐up stroke [WUS]), which renders patients ineligible for IV tPA administered via time‐based treatment algorithms, because it is impossible to establish a reliable time of symptom onset. We performed a systematic review and meta‐analysis of the efficacy and safety of IV tPA compared with normal saline, placebo, or no treatment in patients with WUS using imaging‐based treatment algorithms.

Methods

We searched MEDLINE, Web of Science, and Scopus between January 1, 2006 and April 30, 2020. We included controlled trials (randomized or nonrandomized), observational cohort studies (prospective or retrospective), and single‐arm studies in which adults with WUS were administered IV tPA after magnetic resonance imaging (MRI)‐ or computed tomography (CT)‐based imaging. Our primary outcome was recovery at 90 days (defined as a modified Rankin Scale [mRS] score of 0–2), and our secondary outcomes were symptomatic intracranial hemorrhage (sICH) within 36 h, mortality, and other adverse effects.

Results

We included 16 studies that enrolled a total of 14,017 patients. Most studies were conducted in Europe (37.5%) or North America (37.5%), and 1757 patients (12.5%) received IV tPA. All studies used MRI‐based (five studies) or CT‐based (10 studies) imaging selection, and one study used a combination of modalities. Sixty‐one percent of patients receiving IV tPA achieved an mRS score of 0 to 2 at 90 days (95% confidence interval [CI]: 51%–70%, 12 studies), with a relative risk (RR) of 1.21 compared with patients not receiving IV tPA (95% CI: 1.01–1.46, four studies). Three percent of patients receiving IV tPA experienced sICH within 36 h (95% CI: 2.5%–4.1%; 16 studies), which is an RR of 4.00 compared with patients not receiving IV tPA (95% CI: 2.85–5.61, seven studies).

Conclusions

This systematic review and meta‐analysis suggests that IV tPA is associated with a better functional outcome at 90 days despite the increased but acceptable risk of sICH. Based on these results, IV tPA should be offered as a treatment for WUS patients with favorable neuroimaging findings.