bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost of illness for childhood diarrhea in low- and middle-income countries: a systematic review of evidence and modelled estimates
Authors: Baral Ranju , Nonvignon Justice , Debellut Frédéric , Agyemang Samuel Agyei , Clark Andrew , Pecenka Clint
Published: May 2020

Background

Numerous studies have reported the economic burden of childhood diarrhea in low- and middle-income countries (LMICs). Yet, empirical data on the cost of diarrheal illness is sparse, particularly in LMICs. In this study we review the existing literature on the cost of childhood diarrhea in LMICs and generate comparable estimates of cost of diarrhea across 137 LMICs.

Methods

The systematic literature review included all articles reporting cost estimates of diarrhea illness and treatment from LMICs published between January 2006 and July 2018. To generate country-specific costs, we used service delivery unit costs from the World Health Organization’s Choosing Interventions that are Cost-Effective (WHO–CHOICE database). Non-medical costs were calculated using the ratio between direct medical and direct non-medical costs, derived from the literature review. Indirect costs (lost wages to caregivers) were calculated by multiplying the average GDP per capita per day by the average number of days lost to illness identified from the literature. All cost estimates are reported in 2015 USD. We also generated estimates using the IHME’s service delivery unit costs to explore input sensitivity on modelled cost estimates.

Results

We identified 25 articles with 64 data points on either direct or indirect cost of diarrhoeal illness in children aged < 5 years in 20 LMICs. Of the 64 data points, 17 were on the cost of outpatient care, 28 were on the cost of inpatient care, and 19 were unspecified. The average cost of illness was US$36.56 (median $15.73; range $4.30 – $145.47) per outpatient episode and $159.90 (median $85.85; range $41.01 – $538.33) per inpatient episode. Direct medical costs accounted for 79% (83% for inpatient and 74% for outpatient) of the total direct costs. Our modelled estimates, across all 137 countries, averaged (weighted) $52.16 (median $47.56; range $8.81 – $201.91) per outpatient episode and $216.36 (median $177.20; range $23.77 –$1225.36) per inpatient episode. In the 12 countries with primary data, there was reasonable agreement between our modelled estimates and the reported data (Pearson’s correlation coefficient = .75).

Conclusion

Our modelled estimates generally correspond to estimates observed in the literature, with a few exceptions. These estimates can serve as useful inputs for planning and prioritizing appropriate health interventions for childhood diarrheal diseases in LMICs in the absence of empirical data.
Beta-blocker efficacy across different cardiovascular indications: an umbrella review and meta-analytic assessment
Authors: Ziff Oliver J. , Samra Monica , Howard James P. , Bromage Daniel I. , Ruschitzka Frank , Francis Darrel P. , Kotecha Dipak
Published: May 2020

Background

Beta-blockers are widely used for many cardiovascular conditions; however, their efficacy in contemporary clinical practice remains uncertain.

Methods

We performed a prospectively designed, umbrella review of meta-analyses of randomised controlled trials (RCTs) investigating the evidence of beta-blockers in the contemporary management of coronary artery disease (CAD), heart failure (HF), patients undergoing surgery or hypertension (registration: PROSPERO CRD42016038375). We searched MEDLINE, EMBASE and the Cochrane Library from inception until December 2018. Outcomes were analysed as beta-blockers versus control for all-cause mortality, myocardial infarction (MI), incident HF or stroke. Two independent investigators abstracted the data, assessed the quality of the evidence and rated the certainty of evidence.

Results

We identified 98 meta-analyses, including 284 unique RCTs and 1,617,523 patient-years of follow-up. In CAD, 12 meta-analyses (93 RCTs, 103,481 patients) showed that beta-blockers reduced mortality in analyses before routine reperfusion, but there was a lack of benefit in contemporary studies where ≥ 50% of patients received thrombolytics or intervention. Beta-blockers reduced incident MI at the expense of increased HF. In HF with reduced ejection fraction, 34 meta-analyses (66 RCTs, 35,383 patients) demonstrated a reduction in mortality and HF hospitalisation with beta-blockers in sinus rhythm, but not in atrial fibrillation. In patients undergoing surgery, 23 meta-analyses (89 RCTs, 19,211 patients) showed no effect of beta-blockers on mortality for cardiac surgery, but increased mortality in non-cardiac surgery. In non-cardiac surgery, beta-blockers reduced MI after surgery but increased the risk of stroke. In hypertension, 27 meta-analyses (36 RCTs, 260,549 patients) identified no benefit versus placebo, but beta-blockers were inferior to other agents for preventing mortality and stroke.

Conclusions

Beta-blockers substantially reduce mortality in HF patients in sinus rhythm, but for other conditions, clinicians need to weigh up both benefit and potential risk.
Atrial fibrillation source area probability mapping using electrogram patterns of multipole catheters
Authors: Ganesan Prasanth , Cherry Elizabeth M. , Huang David T. , Pertsov Arkady M. , Ghoraani Behnaz
Published: May 2020

Background

Catheter ablation therapy involving isolation of pulmonary veins (PVs) from the left atrium is performed to terminate atrial fibrillation (AF). Unfortunately, standalone PV isolation procedure has shown to be a suboptimal success with AF continuation or recurrence. One reason, especially in patients with persistent or high-burden paroxysmal AF, is known to be due to the formation of repeating-pattern AF sources with a meandering core inside the atria. However, there is a need for accurate mapping and localization of these sources during catheter ablation.

Methods

A novel AF source area probability (ASAP) mapping algorithm was developed and evaluated in 2D and 3D atrial simulated tissues with various arrhythmia scenarios and a retrospective study with three cases of clinical human AF. The ASAP mapping analyzes the electrograms collected from a multipole diagnostic catheter that is commonly used during catheter ablation procedure to intelligently sample the atria and delineate the trajectory path of a meandering repeating-pattern AF source. ASAP starts by placing the diagnostic catheter at an arbitrary location in the atria. It analyzes the recorded bipolar electrograms to build an ASAP map over the atrium anatomy and suggests an optimal location for the subsequent catheter location. ASAP then determines from the constructed ASAP map if an AF source has been delineated. If so, the catheter navigation is stopped and the algorithm provides the area of the AF source. Otherwise, the catheter is navigated to the suggested location, and the process is continued until an AF-source area is delineated.

Results

ASAP delineated the AF source in over 95% of the simulated human AF cases within less than eight catheter placements regardless of the initial catheter placement. The success of ASAP in the clinical AF was confirmed by the ablation outcomes and the electrogram patterns at the delineated area.

Conclusion

Our analysis indicates the potential of the ASAP mapping to provide accurate information about the area of the meandering repeating-pattern AF sources as AF ablation targets for effective AF termination. Our algorithm could improve the success of AF catheter ablation therapy by locating and subsequently targeting patient-specific and repeating-pattern AF sources inside the atria.
Metabolic abnormalities exacerbate Sjögren’s syndrome by and is associated with increased the population of interleukin–17–producing cells in NOD/ShiLtJ mice
Authors: Hwang Sun-Hee , Park Jin-Sil , Yang SeungCheon , Jung Kyung-Ah , Choi JeongWon , Kwok Seung-Ki , Park Sung-Hwan , Cho Mi-La
Published: May 2020

Background

Sjögren’s syndrome (SS) is an autoimmune disease mediated by lymphocytic infiltration into exocrine glands, resulting in progressive lacrimal and salivary destruction and dysfunctional glandular secretion. Metabolic syndrome influences the immune system. To investigate its relationship with metabolic abnormalities, we evaluated the pathogenesis of SS and the immune cell populations in non-obese diabetic NOD/ShiLtJ mice with type 1 diabetes (T1D).

Methods

To induce metabolic abnormalities, streptozotocin (STZ)—a glucosamine–nitrosourea compound that destroys pancreatic β cells, resulting in T1D—was injected into NOD/ShiLtJ mice. The blood glucose level was measured to evaluate induction of T1D. The severity of SS was assessed by determining the body weight, salivary flow rate, and histologic parameters. The expression levels of proinflammatory factors in the salivary glands, lacrimal gland, and spleen were quantified by real–time PCR. The populations of various T– and B–cell subtypes in the peripheral blood, spleen, and salivary glands were assessed by flow cytometry.

Results

Induction of T1D in NOD/ShiLtJ mice increased both the severity of SS and the levels of proinflammatory cytokines in the salivary glands compared to the controls. Furthermore, the number of interleukin-17–producing immune cells in the peripheral blood, spleen, and salivary glands was increased in STZ- compared to vehicle-treated NOD/ShiLtJ mice.

Conclusions

Metabolic abnormalities play an important role in the development of SS.
Reuma.pt/vasculitis – the Portuguese vasculitis registry
Authors: Ponte Cristina , Khmelinskii Nikita , Teixeira Vítor , Luz Karine , Peixoto Daniela , Rodrigues Marília , Luís Mariana , Teixeira Lídia , Sousa Sandra , Madeira Nathalie , Aleixo Joana A. , Pedrosa Teresa , Serra Sofia , Campanilho-Marques Raquel , Castelão Walter , Cordeiro Ana , Cordeiro Inês , Fernandes Sílvia , Macieira Carla , Madureira Pedro , Malcata Armando , Vieira Romana , Martins Fernando , Sequeira Graça , Branco Jaime C. , Costa Lúcia , Patto José Vaz , da Silva José Canas , Pereira da Silva José A. , Afonso Carmo , Canhão Helena , Santos Maria J. , Luqmani Raashid A. , Fonseca João E.
Published: May 2020

Background

The vasculitides are a group of rare diseases with different manifestations and outcomes. New therapeutic options have led to the need for long-term registries. The Rheumatic Diseases Portuguese Register, Reuma.pt, is a web-based electronic clinical record, created in 2008, which currently includes specific modules for 12 diseases and > 20,000 patients registered from 79 rheumatology centres. On October 2014, a dedicated module for vasculitis was created as part of the European Vasculitis Society collaborative network, enabling prospective collection and central storage of encrypted data from patients with this condition. All Portuguese rheumatology centres were invited to participate. Data regarding demographics, diagnosis, classification criteria, assessment tools, and treatment were collected. We aim to describe the structure of Reuma.pt/vasculitis and characterize the patients registered since its development.

Results

A total of 687 patients, with 1945 visits, from 13 centres were registered; mean age was 53.4 ± 19.3 years at last visit and 68.7% were females. The most common diagnoses were Behçet’s disease (BD) (42.5%) and giant cell arteritis (GCA) (17.8%). Patients with BD met the International Study Group criteria and the International Criteria for BD in 85.3 and 97.2% of cases, respectively. Within the most common small- and medium-vessel vasculitides registered, median [interquartile range] Birmingham Vasculitis Activity Score (BVAS) at first visit was highest in patients with ANCA-associated vasculitis (AAV) (17.0 [12.0]); there were no differences in the proportion of patients with AAV or polyarteritis nodosa who relapsed (BVAS≥1) or had a major relapse (≥1 major BVAS item) during prospective assessment (p = 1.00,p = 0.479). Biologic treatment was prescribed in 0.8% of patients with GCA, 26.7% of patients with AAV, and 7.6% of patients with BD. There were 34 (4.9%) deaths reported.

Conclusions

Reuma.pt/vasculitis is a bespoke web-based registry adapted for routine care of patients with this form of rare and complex diseases, allowing an efficient data-repository at a national level with the potential to link with other international databases. It facilitates research, trials recruitment, service planning and benchmarking.
Extended half-life target module for sustainable UniCAR T-cell treatment of STn-expressing cancers
Authors: Loureiro Liliana R. , Feldmann Anja , Bergmann Ralf , Koristka Stefanie , Berndt Nicole , Máthé Domokos , Hegedüs Nikolett , Szigeti Krisztián , Videira Paula A. , Bachmann Michael , Arndt Claudia
Published: May 2020

Background

Adapter chimeric antigen receptor (CAR) approaches have emerged has promising strategies to increase clinical safety of CAR T-cell therapy. In the UniCAR system, the safety switch is controlled via a target module (TM) which is characterized by a small-size and short half-life. The rapid clearance of these TMs from the blood allows a quick steering and self-limiting safety switch of UniCAR T-cells by TM dosing. This is mainly important during onset of therapy when tumor burden and the risk for severe side effects are high. For long-term UniCAR therapy, the continuous infusion of TMs may not be an optimal setting for the patients. Thus, in later stages of treatment, single infusions of TMs with an increased half-life might play an important role in long-term surveillance and eradication of residual tumor cells. Given this, we aimed to develop and characterize a novel TM with extended half-life targeting the tumor-associated carbohydrate sialyl-Tn (STn).

Methods

The extended half-life TM is composed of the STn-specific single-chain variable fragment (scFv) and the UniCAR epitope, fused to the hinge region and Fc domain of a human immunoglobulin 4 (IgG4) antibody. Specific binding and functionality of the αSTn-IgG4 TM as well as pharmacokinetic features were assessed using in vitro and in vivo assays and compared to the already established small-sized αSTn TM.

Results

The novel αSTn-IgG4 TM efficiently activates and redirects UniCAR T-cells to STn-expressing tumors in a target-specific and TM-dependent manner, thereby promoting the secretion of proinflammatory cytokines and tumor cell lysis in vitro and in experimental mice. Moreover, PET-imaging results demonstrate the specific enrichment of the αSTn-IgG4 TM at the tumor site, while presenting a prolonged serum half-life compared to the short-lived αSTn TM.

Conclusion

In a clinical setting, the combination of TMs with different formats and pharmacokinetics may represent a promising strategy for retargeting of UniCAR T-cells in a flexible, individualized and safe manner at particular stages of therapy. Furthermore, as these molecules can be used for in vivo imaging, they pose as attractive candidates for theranostic approaches.
Neurofeedback for tinnitus: study protocol for a randomised controlled trial assessing the specificity of an alpha/delta neurofeedback training protocol in alleviating both sound perception and psychological distress in a cohort of chronic tinnitus sufferers
Authors: Jensen Martin , Hüttenrauch Eva , Schmidt Jennifer , Andersson Gerhard , Chavanon Mira-Lynn , Weise Cornelia
Published: May 2020

Background

Tinnitus is a particularly common condition and can have debilitating psychological consequences for certain people. Although several interventions have been helpful in teaching individuals to better cope with tinnitus, no cure exists at present. Neurofeedback is an emerging treatment modality in tinnitus. Previous studies, utilising an alpha/delta training protocol, have shown promise. However, they were characterised by small sample sizes and a lack of neurofeedback control conditions. Therefore, the aim of this study is to investigate whether an alpha/delta neurofeedback training protocol, compared to beta/theta neurofeedback or a diary control group, is effective in reducing not only the tinnitus sound perception but also the psychological symptoms associated with the condition.

Methods

The study is designed as a three-armed randomised controlled trial. Participants are randomly assigned to a) an established neurofeedback protocol for tinnitus (alpha/delta training), b) an active control group (beta/theta training) or c) a diary control group. In the 4-week intervention period, participants in both neurofeedback groups undergo 10 sessions, whereas participants in the diary control group complete a bi-weekly diary. The primary outcomes are between group differences in tinnitus sound perception change, as measured with the Tinnitus Magnitude Index (TMI), and changes in tinnitus distress, measured with the Tinnitus Handicap Inventory (THI), 4 weeks after the start of the intervention. Secondary outcome measures include changes in tinnitus distress, sleep quality, depressive symptoms and whether neurofeedback leads to specific power changes in the trained frequency bands.

Discussion

This is the first randomised controlled trial examining the efficacy of an alpha/delta neurofeedback training protocol in reducing tinnitus sound perception and the distress associated with the condition. Compared to former studies, the present study is designed to assess both the specificity of an alpha/delta neurofeedback training protocol by including an active comparator and beta/theta neurofeedback training, in addition to controlling for placebo effects by the inclusion of a diary control group. This study aims to contribute to an understanding of the influences of both specific and non-specific effects in neurofeedback treatment for tinnitus.

Trial registration

ClinicalTrials.gov: NCT03550430. Registered on 27 May 2018.
Sex- and growth-specific characteristics of small for gestational age infants: a prospective cohort study
Authors:   on behalf of the SCOPE Consortium, van der Vlugt Eva R. , Verburg Petra E. , Leemaqz Shalem Y. , McCowan Lesley M. E. , Poston Lucilla , Kenny Louise C. , Myers Jenny , Walker James J. , Dekker Gustaaf A. , Roberts Claire T.
Published: May 2020

Background

Asymmetric fetal growth and male sex are both associated with adverse neonatal outcome. However, less is known about the influence of asymmetric growth and fetal sex within SGA neonates, a group of infants already at increased risk for adverse neonatal outcomes. The aim of the present study was to provide insight into variance in risk factors for SGA in a fetal sex- and growth symmetry-specific way.

Methods

For this prospective, multicenter cohort study, data from the Screening for Pregnancy Endpoints (SCOPE) study were used with 5628 nulliparous participants, of which 633 (11.3%) pregnancies were complicated with SGA and 3376 (60.0%) women had uncomplicated pregnancies. Association between risk factors for SGA, SGA subgroups, and uncomplicated pregnancies were assessed with multivariable analyses.

Results

Prevalence of asymmetric growth varied from 45.8% of SGA infants to 5.5% of infants with a customized birthweight > 90th percentile (p < 0.001). Significantly more SGA males had asymmetric growth compared to SGA female infants (51.2% vs 40.4%, p = 0.009). Maternal pre-pregnancy diet and BMI < 20 and ≥ 30 were significantly associated with symmetric SGA but not with asymmetric SGA. Asymmetric SGA infants had not only lower customized birthweight percentile (4.4 (SD 2.8) vs 5.0 (SD 3.0), p < 0.001), but also lower rates of stillbirth (p = 0.041) and less often Apgar scores < 7 (p = 0.060).

Conclusions

Among SGA infants, low customized birthweight percentiles and male sex are associated with asymmetric growth. Only symmetric SGA is significantly associated with maternal risk factors in early pregnancy. There is a substantial variance in risk factors and neonatal outcomes for SGA based on growth symmetry, implying a different pathogenesis.

Trial registration

ACTRN12607000551493
Evaluation of the accuracy of algorithms to identify soft tissue sarcoma (STS) in administrative claims
Authors: Princic Nicole , McMorrow Donna , Chan Philip , Hess Lisa
Published: May 2020

Background

Lack of using a validated algorithm to select patients is a source of selection bias in oncology studies using administrative claims. The objective of this study to evaluate published algorithms to identify patients with soft tissue sarcoma (STS) in administrative claims and to evaluate new algorithms to improved performance.

Methods

Two cancer populations including STS cases and non-STS controls were selected from the MarketScan Explorys Linked Claims-Electronic Medical Record (EMR) Database between January 1, 2000 and July 31, 2018. Eligible cases had a diagnosis on a clinical record for STS in the EMR while controls had no evidence of STS on any EMR records. Both cases and controls were enrolled in administrative claims during a period of observation and were aged ≥ 18 years. A split sample was used to test and validate algorithms using data from administrative claims. Values for sensitivity, specificity, and positive predictive value (PPV) were calculated for 14 algorithms. Prior literature validating algorithms in administrative claims across other cancer types report both sensitivity and specificity ranging from as low as 73% to as high as 95%. This was used as a benchmark for defining algorithm success.

Results

There were 784 STS cases and 249,062 non-STS cancer controls eligible for analysis. Requiring at least two claims with an ICD-CM diagnosis code for STS achieved a sensitivity of 67% but had a specificity of 72%. Algorithms that required NCCN-recommended systemic treatment for STS improved the specificity to over 90% but dropped the sensitivity to below 20%. Other combinations of diagnostic tests, symptoms, and procedures did not improve performance.

Conclusions

The algorithms tested in this study sample did not achieve sufficient performance and suggest the ability to accurately identify the STS population in administrative data is problematic. Difficulties are likely due to the origin of STS in a variety of locations, the non-specific symptoms of STS, and the common diagnostic tests recommended to diagnose the disease. Future research applying machine learning to examine timing and patterns of variables that comprise the diagnostic process may further investigate the ability to accurately identify STS cases in claims databases.
Use of autologous fascia lata graft to repair a complex corneal ulcer in a mare
Authors: Lores Marcos , Rakestraw Peter , De Rijck Mieke , Yarbrough Thomas
Published: May 2020

Background

Application of an autogenous fascia lata graft in the treatment of keratomalacia in the horse has not been reported. The present case describes the use of an autologous fascia lata graft to surgically treat a complicated corneal ulcer in a horse.

Case presentation

A 12-year-old Arabian mare was admitted to Sharjah Equine Hospital with a history of right eye ulcerative keratitis of unknown duration. Following a week of aggressive medical treatment, the condition deteriorated and a keratectomy and pedicle conjunctival graft were performed. A week later, the conjunctival graft partially dehisced and the ulcer continued to degrade.

In attempting to preserve the integrity of the globe a second grafting procedure was performed when a segment of fascia lata harvested from the ipsilateral hind leg was grafted onto the corneal lesion.

Response to surgery was positive and the mare was discharged from the hospital on Day 31 post diagnosis (17 days after the second surgery) with a comfortable eye.

Follow-up12 months later revealed a comfortable but only partially visual eye due to corneal scarring.

Conclusion

Although the graft actually failed from the point of view of tissue integration, fascia lata appears to be a readily available, effective and affordable autografting material and we believe this technique has potential for short term physical and structural support of severe malacic or other complex corneal ulcers.
The neovaginal microbiome of transgender women post-gender reassignment surgery
Authors: Birse Kenzie D. , Kratzer Kateryna , Zuend Christina Farr , Mutch Sarah , Noël-Romas Laura , Lamont Alana , Abou Max , Jalil Emilia , Veloso Valdiléa , Grinsztejn Beatriz , Friedman Ruth Khalili , Broliden Kristina , Bradley Frideborg , Poliquin Vanessa , Li Fan , Yanavich Carolyn , Burgener Adam , Aldrovandi Grace
Published: May 2020

Background

Gender reassignment surgery is a procedure some transgender women (TW) undergo for gender-affirming purposes. This often includes the construction of a neovagina using existing penile and scrotal tissue and/or a sigmoid colon graft. There are limited data regarding the composition and function of the neovaginal microbiome representing a major gap in knowledge in neovaginal health.

Results

Metaproteomics was performed on secretions collected from the neovaginas (n = 5) and rectums (n = 7) of TW surgically reassigned via penile inversion/scrotal graft with (n = 1) or without (n = 4) a sigmoid colon graft extension and compared with secretions from cis vaginas (n = 32). We identified 541 unique bacterial proteins from 38 taxa. The most abundant taxa in the neovaginas were Porphyromonas (30.2%), Peptostreptococcus (9.2%), Prevotella (9.0%), Mobiluncus (8.0%), and Jonquetella (7.2%), while cis vaginas were primarily Lactobacillus and Gardnerella. Rectal samples were mainly composed of Prevotella and Roseburia. Neovaginas (median Shannon’s H index = 1.33) had higher alpha diversity compared to cis vaginas (Shannon’s H = 0.35) (p = 7.2E−3, Mann-Whitney U test) and were more similar to the non-Lactobacillus dominant/polymicrobial cis vaginas based on beta diversity (perMANOVA, p = 0.001, r2 = 0.342). In comparison to cis vaginas, toll-like receptor response, amino acid, and short-chain fatty acid metabolic pathways were increased (p < 0.01), while keratinization and cornification proteins were decreased (p < 0.001) in the neovaginal proteome.

Conclusions

Penile skin-lined neovaginas have diverse, polymicrobial communities that show similarities in composition to uncircumcised penises and host responses to cis vaginas with bacterial vaginosis (BV) including increased immune activation pathways and decreased epithelial barrier function. Developing a better understanding of microbiome-associated inflammation in the neovaginal environment will be important for improving our knowledge of neovaginal health.
Onset and recovery of ultrasound guided out-of-plane versus in-plane interscalene block in arthroscopic shoulder surgery
Authors: Samir Ghada M. , Ghallab Mahmoud Abd El-Aziz
Published: May 2020

Background

The aim of this study was to assess the out-of-plane versus the in-plane approaches for the interscalene brachial plexus block, as regards the performance time, the onset, the progression and the recovery of sensory block, the onset and progression of the motor block as well as, the postoperative pain score, and the duration of analgesia for arthroscopic shoulder surgery. A total of 60 patients of American Society of Anesthesiologists (ASA) physical status I-II were randomly divided to receive either the in-plane approach (group I), or the out-of-plane approach (group O).

Results

The block performance time was statistically significant shorter in group O. The onset of sensory block was statistically significant faster in group O. The progression of sensory block over the first 20 min was statistically significant fast for C5 and C6 nerve roots in group O. The motor block showed statistically and clinically significant rapid onset and progression in group O. All patients in group O and group I felt no pain in the post-anesthesia care unit (PACU), and the first call for analgesia was at 24 h in both groups.

Conclusion

The out-of-plane approach offers short performance time, rapid onset and progression of sensory and motor blocks, as well as postoperative analgesic effect lasting for 24 h in arthroscopic shoulder surgery.
General hospital services in the UK for adults presenting after self-harm: little evidence of progress in the past 25 years
Authors: House Allan , Owens David
Published: May 2020

Self-harm remains a serious public health concern, not least because of its strong link with suicide. Twenty-five years ago we lamented the deficits in UK services, research and policy. Since then, there has not been nearly enough effective action in any of these three domains. It is time for action.
Hypomagnesuria is Associated With Nephrolithiasis in Patients With Asymptomatic Primary Hyperparathyroidism
Authors: Saponaro Federica , Marcocci Claudio , Apicella Matteo , Mazoni Laura , Borsari Simona , Pardi Elena , Di Giulio Marina , Carlucci Francesco , Scalese Marco , Bilezikian John P , Cetani Filomena
Published: May 2020

Context

The pathogenesis of nephrolithiasis in primary hyperparathyroidism (PHPT) remains to be elucidated. The latest guidelines suggest parathyroidectomy in patients with asymptomatic PHPT with hypercalciuria (> 400 mg/d) and increased stone risk profile.

Objective

The objective of this work is to evaluate the association of urinary stone risk factors and nephrolithiasis in patients with asymptomatic sporadic PHPT and its clinical relevance.

Design

A total of 157 consecutive patients with sporadic asymptomatic PHPT were evaluated by measurement of serum and 24-hour urinary parameters and kidney ultrasound.

Results

Urinary parameters were tested in the univariate analysis as continuous and categorical variables. Only hypercalciuria and hypomagnesuria were significantly associated with nephrolithiasis in the univariate and multivariate analysis adjusted for age, sex, body mass index, estimated glomerular filtration rate, parathyroid hormone, 25-hydroxyvitamin D, serum calcium, and urine volume (odds ratio, OR 2.14 [1.10-4.56]; P = .04; OR 3.06 [1.26-7.43]; P = .013, respectively). Hypomagnesuria remained associated with nephrolithiasis in the multivariate analysis (OR 6.09 [1.57-23.5], P = .009) even when the analysis was limited to patients without concomitant hypercalciuria. The urinary calcium/magnesium (Ca/Mg) ratio was also associated with nephrolithiasis (univariate OR 1.62 [1.27-2.08]; P = .001 and multivariate analysis OR 1.74 [1.25-2.42], P = .001). Hypomagnesuria and urinary Ca/Mg ratio had a better, but rather low, positive predictive value compared with hypercalciuria.

Conclusions

Hypomagnesuria and urinary Ca/Mg ratio are each associated with silent nephrolithiasis and have potential clinical utility as risk factors, besides hypercalciuria, for kidney stones in asymptomatic PHPT patients. The other urinary indices that have been commonly thought to be associated with kidney stones in PHPT are not supported by our results.
Nop9 recognizes structured and single-stranded RNA elements of preribosomal RNA
Authors: Zhang Jun , Teramoto Takamasa , Qiu Chen , Wine Robert N. , Gonzalez Lauren E. , Baserga Susan J. , Tanaka Hall Traci M.
Published: May 2020

Nop9 is an essential factor in the processing of preribosomal RNA. Its absence in yeast is lethal, and defects in the human ortholog are associated with breast cancer, autoimmunity, and learning/language impairment. PUF family RNA-binding proteins are best known for sequence-specific RNA recognition, and most contain eight α-helical repeats that bind to the RNA bases of single-stranded RNA. Nop9 is an unusual member of this family in that it contains eleven repeats and recognizes both RNA structure and sequence. Here we report a crystal structure of Saccharomyces cerevisiae Nop9 in complex with its target RNA within the 20S preribosomal RNA. This structure reveals that Nop9 brings together a carboxy-terminal module recognizing the 5′ single-stranded region of the RNA and a bifunctional amino-terminal module recognizing the central double-stranded stem region. We further show that the 3′ single-stranded region of the 20S target RNA adds sequence-independent binding energy to the RNA–Nop9 interaction. Both the amino- and carboxy-terminal modules retain the characteristic sequence-specific recognition of PUF proteins, but the amino-terminal module has also evolved a distinct interface, which allows Nop9 to recognize either single-stranded RNA sequences or RNAs with a combination of single-stranded and structured elements.
The nexus between water sufficiency and water-borne diseases in cities in Africa: a scoping review protocol
Authors: Mutono Nyamai , Wright James , Mutembei Henry , Muema Josphat , Thomas Mair , Mutunga Mumbua , Thumbi Samuel Mwangi
Published: May 2020

Introduction: Currently, an estimated two thirds of the world population is water insufficient. As of 2015, one out of every five people in developing countries do not have access to clean sufficient drinking water. In an attempt to share the limited resource, water has been distributed at irregular intervals in cities in developing countries. Residents in these cities seek alternative water sources to supplement the inadequate water supplied. Some of these alternative sources of water are unsafe for human consumption, leading to an increased risk in water-borne diseases. Africa contributes to 53% of the diarrheal cases reported globally, with contaminated drinking water being the main source of transmission. Water-borne diseases like diarrhea, cholera, typhoid, amoebiasis, dysentery, gastroenteritis, cryptosporidium, cyclosporiasis, giardiasis, guinea worm and rotavirus are a major public health concern. The main objective of this scoping review is to map the available evidence to understand the sources of water among residents in cities in Africa and the relationship between clean water sufficiency and water-borne diseases in urban Africa.

Methods and analysis: The search strategy will identify studies published in scientific journals and reports that are directly relevant to African cities that have a population of more than half a million residents as of 2014 AND studies on the ten emerging water-borne diseases, which are diarrhea, cholera, typhoid, amoebiasis, dysentery, gastroenteritis, cryptosporidium, cyclosporiasis, giardiasis, guinea worm and rotavirus.

Ethics and dissemination: This scoping review did not require any formal ethical approval. The findings will be published in a peer-reviewed journal.
Territorialidades y representaciones sociales superpuestas en la dicotomía agua vs. oro: El conflicto socioambiental por minería industrial en el páramo de Santurbán
Authors: Méndez Villamizar Raquel , Mejía Jerez Andrea , Acevedo Tarazona Álvaro
Published: May 2020

El páramo de Santurbán (Colombia) es un espacio biogeográfico y biodiverso, y centro de disputas sociales, políticas y económicas. Este artículo analiza las representaciones del agua, el oro y la superposición de las territorialidades de distintos grupos sociales en el año 2011 como efecto del conflicto socioambiental por minería industrial. Para ello se realizó un ejercicio de interpretación narrativa de entrevistas semiestructuradas a pobladores y colectivos sociales de los municipios de Vetas y California y de la ciudad de Bucaramanga, quienes argumentaron sobre la importancia del agua y del oro en su vida cotidiana. La población de Santurbán concibe el agua como fundamental para su existencia y al oro, para su economía, las tradiciones y la cultura. Mientras tanto, para la población de Bucaramanga, la representación del agua se relaciona con la ética ambientalista. Esta superposición desencadena conflictos antes invisibilizados entre dos poblaciones vecinas que se han beneficiado del páramo conjuntamente.
More than Words in Medical Question-and-Answer Sites: A Content-Context Congruence Perspective
Authors: Peng Chih-Hung , Yin Dezhi , Zhang Han
Published: May 2020

Application Abstract
Partial Demand Information and Commitment in Dynamic Transportation Procurement
Authors: Boada-Collado Pol , Chopra Sunil , Smilowitz Karen
Published: May 2020

This paper analyzes a decision process of planning transportation procurement for a distribution lane given limited information regarding future demand for transportation services and a specified commitment horizon for procurement contracts. In contrast to variants in which either full demand information or no demand information is known over the planning horizon, our work considers the value of demand visibility for a short horizon in the future (i.e., the value of partial information). Our work also considers a commitment horizon that is much shorter than the planning horizon. We show that the availability of partial information fundamentally changes the contracting policies in the presence of such commitment horizons, and if used optimally, this information can be highly valuable. Partial visibility of demand can increase the willingness of the decision maker to commit to contracts and expand the range of capacity levels selected in settings where the capacity level of a contract is a decision variable. We also identify settings in which the value of partial information is negligible, reducing the incentive of managers to acquire additional demand information for future periods. Finally, we show that with seasonal demand, information is leveraged by properly coordinating with expected demand shocks (e.g., Black Friday) using tailored strategies.
Could mindfulness activity improve occupational health in UK paramedics?
Authors: Forster Christopher
Published: May 2020

Emerging research is supporting the implementation of mindfulness-based strategies for NHS staff. It has been shown that, by spending 10 minutes daily on the activity, health professionals can improve their emotional and cognitive functioning, while reducing work-related rumination. Through an exploratory multi-methods approach, this study sets out to quantify the occupational health levels of paramedics, and establish their appreciation of both their employer's health and wellbeing policy and mindfulness as a concept, for the overall purpose of gaining a qualitative insight into whether mindfulness activity could improve occupational health. Paramedics reported high levels of occupational stress, coupled with minimal levels of knowledge or experience of mindfulness as a health-promoting concept. Structured application of mindfulness strategies within prehospital care may promote a range of health benefits for paramedics, lead to improved organisational efficiency for trusts and support positive outcomes for patients.
Prehospital neuromuscular blockade post OHCA: UK's first paramedic-delivered protocol
Authors: Durham Mark , Westhead Pete , Griffiths David , Lyon Richard , Lau-Walker Margaret
Published: May 2020

Background:

Since 2016, critical care paramedics from the South East Coast Ambulance Service have offered neuromuscular blockade to patients for ventilatory/airway control after cardiac arrest.

Aims:

To examine the first cases of paramedic-delivered neuromuscular blockade, and evaluate the prevalence of its use and safety.

Methods:

Retrospective service evaluation of patients receiving post-arrest paralysis during the study period from 1 April 2016 until 31 July 2017.

Findings:

The study included 127 patients. The mean age of administration was 63 years, mean weight was 80 kg (SD: 19 kg), dose was 1 mg/kg and median time from rocuronium administration to hospital was 32 minutes (IQR 20–43 minutes). Three patients (2.3%) experienced a minor adverse incident. There were no major airway complications, nor other significant adverse incidents. Thirty-seven patients (31%) survived to discharge.

Conclusion:

From this patient group, paramedic-administered rocuronium in intubated patients who have experienced a cardiac arrest and a return of spontaneous circulation appears to be safe, but further interventional research is required to determine whether this improves patient outcomes.
Use of co-amoxiclav for the treatment of dog bites
Authors: Thomas Marc Gildas
Published: May 2020

A large number of people are bitten by dogs—approximately 19 in every 1000 people in the UK per year with even higher proportions in France and the United States. Co-amoxiclav is the most effective antibiotic treatment following a dog bite as it covers the most likely polymicrobial aerobic and anaerobic organisms that infect dog bite wounds (Staphylococci, Streptococci and Pasteurella). Pasteurella is the most infective pathogen in a dog bite so effective antibiotic treatment against it is essential to prevent a metastatic infection. This article explores the normal physiology of human skin including the pathophysiology after sustaining a dog bite. It also examines the pharmacology of co-amoxiclav including critically reviewing the current evidence for the effectiveness of its use in this field as a first-line and prophylactic oral antibiotic treatment.
Sacral fractures: issues, challenges, solutions
Authors: Santolini Emmanuele , Kanakaris Nikolaos K. , Giannoudis Peter V.
Published: May 2020

Sacral fractures are a heterogeneous group of fractures occurring in young people following road traffic accidents and falls from height, or in the elderly with osteoporosis following trivial trauma. This heterogeneity, combined with the low incidence of sacral fractures, determines a lack of experience amongst physicians, often leading to misdiagnosis, underestimation and inadequate treatment. The diagnosis should be made by assessing specific features during the clinical presentation, while computed tomography (CT) scan continues to be the choice of investigation. Sacral fractures can be treated non-operatively or surgically. Non-operative treatment is based on rest, pain relief therapy and early mobilization as tolerated. Surgical techniques can be split into two main groups: posterior pelvic fixation techniques and lumbopelvic fixation techniques. Anterior pelvic fixation techniques should be considered when sacral fractures are associated with anterior pelvic ring injuries, in order to increase stability and reduce the risk of posterior implant failure. To improve fracture reduction, different solutions could be adopted, including special positioning of the patient, manipulation techniques and use of specific reduction tools. Patients suffering from spinopelvic dissociation with associated neurologic lesions hardly ever recover completely, with residual lower-limb neurologic sequelae, urinary problems and sexual disfunction. Herein, we present issues, challenges and solutions related to the management of sacral fractures.

Cite this article: EFORT Open Rev 2020;5:299-311. DOI: 10.1302/2058-5241.5.190064
Slide-free clinical imaging of melanin with absolute quantities using label-free third-harmonic-generation enhancement-ratio microscopy
Authors: Sun Chi-Kuang , Wu Pei-Jhe , Chen Sheng-Tse , Su Yu-Hsiang , Wei Ming-Liang , Wang Chiao-Yi , Gao Hao-Cheng , Sung Kung-Bing , Liao Yi-Hua
Published: May 2020

The capability to image the 3D distribution of melanin in human skin in vivo with absolute quantities and microscopic details will not only enable noninvasive histopathological diagnosis of melanin-related cutaneous disorders, but also make long term treatment assessment possible. In this paper, we demonstrate clinical in vivo imaging of the melanin distribution in human skin with absolute quantities on mass density and with microscopic details by using label-free third-harmonic-generation (THG) enhancement-ratio microscopy. As the dominant absorber in skin, melanin provides the strongest THG nonlinearity in human skin due to resonance enhancement. We show that the THG-enhancement-ratio (erTHG) parameter can be calibrated in vivo and can indicate the melanin mass density. With an unprecedented clinical imaging resolution, our study revealed erTHG-microscopy’s unique capability for long-term treatment assessment and direct clinical observation of melanin’s micro-distribution to shed light into the unknown pathway and regulation mechanism of melanosome transfer and translocation.
Near-field analysis of bound states in the continuum in photonic crystal slabs
Authors: Dai Shiwei , Hu Peng , Han Dezhuan
Published: May 2020

Bound states in the continuum (BICs) can be derived from a generalized waveguide condition in which the total internal reflection is substituted by coherent perfect reflection. Coherent perfect reflection can occur in the truncated photonic crystal (PhC) due to the interference of different Bloch modes. Based on the coherent reflection, BICs can be constructed by the bulk Bloch modes of PhC slabs. In contrast to the determination of BICs from the topological vortices of far-field radiation, this interpretation from coherent reflection can give the spatial field profile in detail in the near field. We show that the BICs can be characterized by the indices (or number of nodes) of their constituent Bloch modes. Moreover, all the guided resonances in addition to BICs can also be labelled by these mode indices. It is found that for the guided resonances the mode indices can change suddenly on the same frequency band. Our results may have potential applications in guided-wave optics and enhanced light-matter interaction.
Femtosecond synchronization of multiple mode-locked lasers and a microwave oscillator by multicolor electro-optic sampling
Authors: Kwon Dohyeon , Jeon Chan-Gi , Kim Dohyun , Jeon Igju , Kim Jungwon
Published: May 2020

Simple multicolor electro-optic sampling-based femtosecond synchronization of multiple mode-locked lasers is demonstrated. Parallel timing error detection between each laser and a common microwave is achieved by wavelength division multiplexing and demultiplexing. The parallel timing error detection enables simultaneous femtosecond synchronization of more than two mode-locked lasers to the microwave oscillator, even when the lasers have different repetition rates. The residual root-mean-square (rms) timing jitter of laser–laser synchronization measured by an optical cross correlator is 2.6 fs (integration bandwidth, 100 Hz–1 MHz), which is limited by the actuator bandwidth in the laser oscillator. The long-term rms timing drift and frequency instability of laser–microwave synchronization are 7.1 fs (over 10,000 s) and

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(over 2000 s averaging time), respectively. As a versatile and reconfigurable tool for laser–laser and laser–microwave synchronization, the demonstrated method can be used for various applications ranging from ultrafast x-ray and electron science facilities to dual- and triple-comb spectroscopy.
Laboratory water-window x-ray microscopy
Authors: Kördel Mikael , Dehlinger Aurélie , Seim Christian , Vogt Ulrich , Fogelqvist Emelie , Sellberg Jonas A. , Stiel Holger , Hertz Hans M.
Published: May 2020

Soft x-ray microscopy in the water window

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) is an emerging and unique tool for 2D and 3D imaging of unstained intact cellular samples in their near-native state with few-10-nm detail. However, present microscopes rely on the high x-ray brightness of synchrotron-radiation sources. Having access to water-window microscopy in the home laboratory would increase the impact and extend the applicability of the method. In the present paper, we review three decades of efforts to build laboratory water-window microscopes and conclude that the method is now reaching the maturity to allow biological studies. The instruments as well as their key components are quantitatively and qualitatively compared. We find that the brightness and the reliability of the laboratory source are the most critical parameters, but that the optics as well as the sample preparation also must be optimized to enable high-resolution imaging with adequate exposure times. We then describe the two sister microscopes in Stockholm and Berlin, which allow reliable high-resolution biological imaging with short exposure times of a few tens of seconds in 2D and a few tens of minutes in 3D. They both rely on a liquid-jet laser-plasma source combined with high-reflectivity normal-incidence multilayer condenser optics, high-resolution zone-plate imaging optics, CCD detection, and cryogenic sample handling. Finally, we present several examples of biological imaging demonstrating the unique properties of these instruments.