bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of the Medial Patellofemoral Ligament Origin on the Distal Femur to the Distal Femoral Physis: A Systematic Review
Authors: Sochacki Kyle R. , Shea Kevin G. , Varshneya Kunal , Safran Marc R. , Abrams Geoffrey D. , Donahue Joseph , Sherman Seth L.
Published: February 2020

Background:

The relationship between the medial patellofemoral ligament (MPFL) and the distal femoral physis has been reported in multiple studies.

Purpose:

To determine the distance from the MPFL central origin on the distal femur to the medial distal femoral physis in skeletally immature participants.

Study Design:

Systematic review.

Methods:

A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Multiple databases were searched for studies investigating the anatomic origin of the MPFL on the distal femur and its relationship to the medial distal femoral physis in skeletally immature participants. Study methodological quality was analyzed with the Anatomical Quality Assessment tool, with studies categorized as low risk, high risk, or unclear risk of bias. Continuous variable data were reported as mean ± SD. Categorical variable data were reported as frequency with percentage.

Results:

Seven articles were analyzed (298 femurs, 53.7% male patients; mean age, 11.7 ± 3.4 years). There was low risk of bias based on the Anatomical Quality Assessment tool. The distance from the MPFL origin to the distal femoral physis ranged from 3.7 mm proximal to the physis to 10.0 mm distal to the physis in individual studies. Six of 7 studies reported that the MPFL origin on the distal femur lies distal to the medial distal femoral physis in the majority of specimens. The MPFL originated distal to the medial distal femoral physis in 92.8% of participants at a mean distance of 6.9 ± 2.4 mm.

Conclusion:

The medial patellofemoral ligament originates distal to the medial distal femoral physis in the majority of cases at a mean proximal-to-distal distance of 7 mm distal to the physis. However, this is variable in the literature owing to study design and patient age and sex.
Value of CT Imaging in the Differentiation of Gastric Leiomyoma From Gastric Stromal Tumor
Authors: Wang Jian , Zhou Xiaoxuan , Xu Fangyi , Ao Weiqun , Hu Hongjie
Published: February 2020

Purpose:

To discuss significant computed tomography (CT) findings that differentiate gastric leiomyomas (GLs) from small gastric stromal tumors (GSTs).

Methods:

One hundred sixty cases with pathologically proven GLs (n = 50) and GSTs (n = 110) with comprehensive CT images were enrolled in this retrospective study. Computed tomography findings (ie, size, location, contour, growth pattern, enhancement degree, necrosis, ulceration, calcification, and lymph nodes) were analyzed through the χ2 or Fisher exact test, independent T test, and multivariate (logistic regression) analysis. Sensitivity and specificity were also calculated.

Results:

Features of cardia location, endophytic growth, homogeneous gradual enhancement, absent of necrosis, long diameter less than 24 mm, short diameter less than 20 mm, unenhanced CT value larger than 35.2 Hounsfield units (HU), portal venous phase CT value larger than 67.4 HU, and enhancement degree of arterial and venous phase less than 16.2 HU and 32.4 HU were found to be statistically significant between GLs and small GSTs ( P < .05). On multivariate analysis, cardia location, endophytic growth, and homogeneous gradual enhancement were independent predictive factors for GLs and small GSTs.

Conclusion:

These 10 CT criteria are very helpful to differentiate GLs from small GSTs. Especially cardia location, endophytic growth, and homogeneous gradual enhancement are of high value in differential diagnosis.
Nonprofit Care Work as Social Glue: Creating and Sustaining Social Reproduction in the Context of Austerity/Late Neoliberalism
Authors: Baines Donna , Cunningham Ian , Kgaphola Innocentia , Mthembu Senzelwe
Published: February 2020

This article will bring together the social glue concept of social reproduction and a feminist analysis of civil society to the study of nonprofit care work in order to cast analytic light on the dynamics of care work in the nonprofit sector and contribute to theorizing care work, to identify and theorize aspects of nonprofit care work which reproduce and sustain social glue, and to supplement theory on civil society. Drawing on qualitative interviews with nonprofit care workers in South Africa and Scotland, this article argues that care work, in general, and nonprofit care work, more specifically, are key components of civil society and central to the gendered social glue that holds societies together. We argue that nonprofit care workers are part a distinctive but porous set of social relations and have their own unique way of sustaining social bonds in the context of late neoliberalism. The article looks closely at three dynamics of social glue in nonprofit care work, namely, empowerment, emotional/personal costs, and unpaid work. We argue that nonprofit care workers find micro ways of resisting the erosion of social glue and reweaving the social fabric through care and relationship and further that these forms of resistance may sustain much needed social bonds until larger social transformation is possible.
Intimate Partner Violence Among Women Accessing HIV-Care Services at Tertiary Hospitals in Ogun State, Nigeria: Implications for Policy and Practice
Authors: Abiodun Olumide , Sodeinde Kolawole , Bamidele Fikayo , Ojinni Yejide , Adekeye John , Ohiaogu Faith , Mbonu Fortunate
Published: February 2020

Intimate partner violence is both a predisposing factor for and sequelae of HIV infection. It is more likely for HIV-positive women to experience intimate partner violence compared with HIV-negative women. Previous researches have described the other risk factors for intimate partner violence. This cross-sectional study identified the correlates of intimate partner violence among HIV-positive women accessing HIV-care. We interviewed 458 women accessing HIV-care at the three tertiary hospitals in Ogun State, Nigeria. Trained research assistants conducted 10-min structured interviews with validated questionnaires. We carried out descriptive, bivariate, and regression analyses. We used the backward elimination technique to build a model to predict the experience of intimate partner violence (IPV) within the preceding 12 months. We set the level of significance at .05. A total of 23 (5.02%) participants reported IPV within the preceding 12 months, while the prevalence of lifetime intimate partner violence was 24.02%. Younger age, the experience of IPV in previous relationships, and having multiple sex partners were related to the experience of IPV within the preceding 12 months ( p < .05). Also, the partners’ age, alcohol intake, and current smoking status were associated with the experience of IPV within the preceding 12 months ( p < .05). After regression analysis, participants’ age (adjusted odds ratio [AOR] = 0.892, 95% confidence interval [CI] = [0.831, 0.957]), experience of IPV in previous relationship (AOR = 12.841, 95% CI = [4.303, 38.318]), and partners’ current smoking status (AOR = 4.874, 95% CI = [1.252, 18.969]) retained association with the experience of IPV within the preceding 12 months. IPV among HIV-positive women accessing HIV-care occurs in a complicated, context-specific way. Routine HIV strategies and services should include interventions that involve men and address gender power imbalances. For effectiveness, specific interventions must consider women’s’ specific context and characteristics.
Crowdfunding Acts as a Funding Substitute and a Legitimating Signal for Nonprofit Performing Arts Organizations
Authors: Alexiou Kostas , Wiggins Jennifer , Preece Stephen B.
Published: February 2020

This research examines the relationship between crowdfunding campaigns by nonprofit performing arts organizations and their overall fundraising portfolio. Using a dataset compiled from the CrowdBerkeley Initiative and the Cultural Data Project, we find an important link between campaign success and organization age. For young organizations, crowdfunding success attracts funding in the subsequent year, while a failed campaign significantly hampers the organization’s ability to raise funds, suggesting that crowdfunding acts as a legitimating signal. In contrast, older organizations appear to be insulated from the negative effects of a failed campaign. In addition, higher amounts raised in the campaign are associated with a substitution or “crowding out” effect for other types of funding for young organizations, but this effect reverses for older organizations. This suggests that crowdfunding should not only be considered a tool for younger organizations, but also holds promise for established organizations.
Experimental and numerical assessment of oblique loading quasi-static testing of railway anticlimbers
Authors: Moreno C , Reid S , Williams T
Published: February 2020

An oblique loading angle test was devised in order to subject the anticlimbers of railway vehicles to a predetermined perpendicular load as well as a predetermined bending moment. The motivation for this type of test was the Standard and industry requirements for anticlimbing devices to prevent overriding and resist a determined perpendicular force while dissipating energy. Anticlimbing units, based on shrinking circular deformation tubes, were subjected to compression tests. The oblique loading was applied by placing the anticlimbing unit on a plate at an angle to the centreline of the unit. A numerical model was validated against the test results, in order to infer the bending moment subjected to the anticlimber unit. The bending moment on the anticlimbers was expected to be fully determined by the perpendicular force and the length of the tube. The predicted bending moment measured by the validated numerical model was smaller than anticipated and was potentially unpredictable. The discrepancy was caused by the irregular distribution of the normal force at the interface of the test machine and the anticlimber head. As a result, the devised angle test was proved unsuitable to induce a consistent and predictable bending moment on the anticlimber units of railway vehicles.
Evolving phenotype of systemic lupus erythematosus in Caucasians: low incidence of lupus nephritis, high burden of neuropsychiatric disease and increased rates of late-onset lupus in the ‘Attikon’ cohort
Authors: Nikolopoulos D , Kostopoulou M , Pieta A , Karageorgas T , Tseronis D , Chavatza K , Flouda S , Rapsomaniki P , Banos A , Kremasmenou E , Tzavara V , Katsimbri P , Fanouriakis A , Boumpas D T
Published: February 2020

Objective

This study aimed to analyse the phenotype of systemic lupus erythematosus (SLE) at first presentation and during follow-up in a newly established SLE cohort based at ‘Attikon’ University Hospital. The hospital combines primary, secondary and tertiary care for the region of Western Attica, Greece.

Methods

This study comprised a mixed prevalent and incident cohort of 555 Caucasian patients diagnosed with SLE according to American College of Rheumatology 1997 criteria and/or the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria. Demographic and clinical characteristics, patterns of severity, treatments and SLICC damage index were recorded for each patient at the time of diagnosis and at last evaluation.

Results

The mean age at lupus diagnosis was 38.3 years (standard deviation = 15.6 years), with a median disease duration at last follow-up of two years (interquartile range 1-11). At initial presentation, the most common ‘classification’ manifestations were arthritis (73.3%), acute cutaneous lupus (65%) and unexplained fever (25%), while among symptoms not included in any criteria set, Raynaud’s phenomenon (33%) was the most common. Kidney and neuropsychiatric involvement as presenting manifestations were present in 10.3% and 11.5% cases, respectively. Irreversible damage accrual was present in 17.8% within six months of disease diagnosis, attributed mainly to thrombotic and neuropsychiatric disease. At last evaluation, 202 (36.4%) patients had developed severe disease, of whom more than half were treated with pulse cyclophosphamide.

Conclusion

In this cohort of Caucasian patients, lupus nephritis is not as common as in older cohorts, while neuropsychiatric disease is emerging as a major frontier in lupus prevention and care. These data may help to document changes in the natural history and treatment of SLE over time and may have implications for its early recognition and management.
Book review: Jasodhara Bagchi, Interrogating Motherhood
Authors: Agnihotri Indu
Published: February 2020

Jasodhara Bagchi, Interrogating Motherhood. New Delhi: SAGE/Stree, 2017, 140 pages, ₹345. ISBN: 9789381345177.
UN Peacekeeping, Responsibility to Protect and Humanitarian Intervention
Authors: Krishnan S.
Published: February 2020

The question of armed intervention on behalf of the international community, in the internal affairs of a state against the wishes of the government of that state, in order to prevent widespread death or suffering among the population, is not a new one. Indeed Imperial Rome grappled with the same problems in Dalmatia and Judaea 2,000 years ago, as the international community does in those same regions today. How effective are peacekeeping operations in preventing and stopping violence? Is there an alternative to United Nations (UN) and regional peacekeeping operations? The practice of UN peacekeeping is evolving in many instances into robust peacemaking actions with a positive responsibility to protect (R2P) civilians within the field of operations. The R2P (and ‘responsibility while protecting’ (RwP)) concept sets out a key principle to enable the international community to prevent atrocity crimes. Since its emergence, however, there have been intense discussions over how to put the principle into practice. Some aspects of the concept remainf unclear, including how to undertake, as the last resort, the use of military force. These issues must be considered within the boundaries set by R2P which seek at all costs to avoid the use of force for other reasons than ceasing mass atrocity crimes. The use of force, therefore – including possible military action by the international community, given growing international reluctance to accept grave threats to peace and security, including mass crimes against defenceless populations – has to be thoroughly analysed and comprehended. This article presents an analysis of the development of civilian peacekeeping, its relevance in the field of conflict resolution and its autonomy from multidimensional peacekeeping, championed by the UN.
Program Design and the Development of Students’ Global Perspectives in Faculty-Led Short-Term Study Abroad
Authors: Whatley Melissa , Landon Adam C. , Tarrant Michael A. , Rubin Donald
Published: February 2020

This study explores connections between design features of faculty-led short-term study abroad programs and resulting changes in students’ global perspectives. Over 2,000 students provided data for this study, completing the Global Perspective Inventory (GPI) before and after studying abroad. Results indicated that program features such as participation in an internship and opportunities for reflection are positively associated with global perspective development while abroad, whereas features such as number of students traveling together and coursework in English are negatively associated with such development. Given the increasing numbers of students who participate in faculty-led short-term abroad programs, research that provides evidence-based recommendations concerning program design is essential to enhancing global perspectives through study abroad.
Taxonomy of Seniors’ Needs for Food and Food Assistance in the United States
Authors: Warren Andrea M. , Frongillo Edward A. , Alford Shana , McDonald Erin
Published: February 2020

Food insecurity results in poor health among seniors. Food and nutrition assistance targeted to seniors experiencing or at risk of food insecurity prevents poor health outcomes and enables seniors to age in place. Currently, the primary modes of service delivery are targeted to seniors who are older and frailer than average, rendering these modes less responsive to the needs of the broader population of food-insecure seniors and limiting the preventive potential of food assistance. This study aimed to understand needs among seniors for food and food assistance and to develop a comprehensive taxonomy for these needs. The taxonomy depicts seniors’ self-identified needs that relate to their ability to access and use food and nutrition assistance across three domains: physical abilities, consuming food, and access and use of transportation. The results of this study are intended to provide in-depth information to support effective alignment of programs with seniors’ needs.
Dose-Dependent Hyperkalemia Among Hospitalized, HIV-Infected Patients Receiving Sulfamethoxazole/Trimethoprim
Authors: Caulder Celeste R. , Kocherla Caitlin S. , Qureshi Zaina P. , Magagnoli Joseph , Bookstaver P. Brandon
Published: February 2020

Background: Sulfamethoxazole-trimethoprim (SXT) therapy is commonly used in HIV-infected patients and is associated with hyperkalemia and elevated serum creatinine (SCr). Objective: The purpose of this study was to examine the frequency of hyperkalemia and elevated SCr in hospitalized, HIV-infected patients receiving SXT. Methods: This was a retrospective, single-center cohort study. HIV-infected hospitalized patients receiving a minimum of 3 consecutive days of SXT were included. Patients were grouped according to high dose (≥10 mg/kg/d) and low dose (<10 mg/kg/d) trimethoprim. The primary end point was the frequency of hyperkalemia, severe hyperkalemia, and elevated SCr. Secondary end points included an evaluation of concomitant potassium-altering medications and concomitant nephrotoxic drugs. Results: A total of 100 consecutive patients were selected from all possible patients who met inclusion criteria. Overall, 47 patients experienced at least 1 adverse drug event (ADE) of either hyperkalemia or increased SCr, with 20 patients experiencing these ADEs in the low-dose group and 27 patients experiencing these ADEs in the high-dose group ( P = 0.229). The ADEs of hyperkalemia or increased SCr occurred after a shorter period (5.5 vs 8.7 days) in the high-dose group ( P = 0.049). Overall frequency of elevated SCr was 24% and of elevated serum K was 36%. Hyperkalemia requiring a therapeutic intervention occurred in 12 patients in the high-dose group compared with 2 in the low-dose group ( P = 0.009). Conclusion and Relevance: Rates of elevated SCr and hyperkalemia in hospitalized HIV-infected patients receiving SXT are significant. Hyperkalemia requiring intervention is more common in patients receiving high-dose SXT.
Dazzle camouflage as queer counter conduct
Authors: Lingel Jessica
Published: February 2020

Developed as an anti-surveillance strategy during World War I, dazzle camouflage used sharply contrasting colors to disguise ships in the British navy from enemy observation. Unlike traditional camouflage that was meant to keep one’s forces or weaponry hidden, dazzle camouflage used hypervisibility to deflect attention, making it impossible to detect a ship’s movements. In this article, I develop the concept of dazzle camouflage as a form of queer counter-conduct, arguing that queer subjectivity offers a generative vantage point for theorizing resistance to the hegemonic gaze. I draw on three forms of queer protest against everyday surveillance: Chelsea Manning’s response to trolling on Twitter, drag queen practices of reading, and a pair of art projects from visual artist Zach Blas. Taken together, these practices allow me to characterize dazzle camouflage as leveraging aesthetic playfulness and boundary work. Conceptually, my goal is to bring together surveillance studies and queer theory as frameworks for building a more robust account of dazzle camouflage, and moreover, an account that can be instructive for queer activism in a context of everyday digital surveillance.
The Association Between Elevated Foot Skin Temperature and the Incidence of Diabetic Foot Ulcers: A Meta-Analysis
Authors: Ena Javier , Carretero-Gomez Juani , Arevalo-Lorido Jose Carlos , Sanchez-Ardila Carmen , Zapatero-Gaviria Antonio , Gómez-Huelgas Ricardo
Published: February 2020

Prior to the appearance of any foot ulcer, there is an increase in the local temperature due to the presence of an underlying inflammatory process. The use of thermometry to identify inflammation could make patients increase preventive measures until the inflammation disappears. We carried out a meta-analysis to determine the effectiveness of the daily measurement of the foot temperature in 6 points to prevent the occurrence of foot ulcers in patients with diabetes. Patients with temperature differences >4°F (2.2°C) between left and right corresponding sites should reduce activity and increase preventive measures until temperature is normalized. We searched the literature in MEDLINE, EMBASE, Cochrane Library, Web of Knowledge, and clinicaltrials.gov. We have only included randomized clinical trials where individuals were assigned to receive enhanced care (temperature measurement and standard care) versus standard care (education, self-care practices, and periodic clinical visits). We found 4 trials comprising 462 patients from the United States and Norway that met our inclusion criteria. The duration of follow-up varied from 4.5 to 15 months. Overall, 18 (7.9%) subjects in the enhanced foot care group and 53 (22.6%) in the standard foot care group developed foot ulcers (pooled risk ratio = 0.37; 95% confidence interval = 0.21-0.66; P = .0008; percentage of heterogeneity [ I2], 25%; P = .26). The number needed to treat was 7 (95% confidence interval = 5-11). The results were robust after analysis by subgroups according to the potential risk of bias in the studies and the duration of follow-up.
Interrater Reliability of Dynamic Muscle Testing After Breast Cancer Surgery in Women at High Risk of Lymphedema: To Improve Quality in Clinical Practice
Authors: Korsholm-Rosfort Tina , Larsen Simone , Aagaard Thomas , Ammitzbøll Gunn , Dalton Susanne O.
Published: February 2020

Background: The purpose of this study is to determine the interrater reliability of dynamic muscle tests in the early rehabilitation phase in women after breast cancer surgery with axillary lymph node dissection (ALND) based on the “preventive intervention against lymphedema after breast cancer” (LYCA) randomised controlled trial. Methods: Fifteen women treated with breast cancer surgery including ALND were recruited from participants in the LYCA trial. In this interrater reliability study, women were tested in 4 dynamic muscle tests by 2 physiotherapists at a Capital Hospital in Denmark. Intraclass correlation coefficients (ICCs) with 95% confidence intervals (CIs) was used to assess the relative reliability between raters. A Bland-Altman plot and limits of agreement were calculated to describe the absolute reliability. Results: All 6 subtests displayed high interrater reliability. ICC values were: leg press 0.96 (95% CI = 0.87-0.99), elbow flexion (contralateral) 0.94 (0.83-0.98), elbow flexion (affected arm) 0.93 (0.80-0.98), elbow extension 0.80 (0.41-0.93), shoulder abduction (contralateral) 0.89 (0.68-0.96), and shoulder abduction (affected arm) 0.91 (0.74-0.97). Cumulated interrater reliability for the test battery was very high (ICC = 0.99, 95% CI = 0.990-1.0). The absolute reliability of this study was considered high, and the absence of large shifts between mean and the line of 0 difference suggest no systematic bias that could influence clinical interpretation. Conclusions: The dynamic muscle tests evaluated in this study had high interrater reliability and can be used reliably in women in the postoperative phase after breast cancer surgery with ALND.
Sutureless Closure of Arterial Cannulation Sites
Authors: Pasrija Chetan , Bernstein Daniel A. , Rice Maryjoe , Tran Douglas , Morales David , Grintz Todd , Deatrick Kristopher B. , Gammie James S. , Madathil Ronson , Kaczorowski David J.
Published: February 2020

Objective

Percutaneous femoral cannulation for venoarterial extracorporeal membrane oxygenation (ECMO) is commonly performed but percutaneous removal of arterial cannulas has not been broadly accepted. We hypothesized that a system that allows endovascular access to ECMO circuits along with the MANTA® large-bore vascular closure device could be used to successfully close arterial ECMO cannulation sites in a large animal model.

Methods

Yorkshire swine (40 to 60 kg, n = 2) were used for this study. In the first swine, the infrarenal abdominal aorta was exposed. The aorta was cannulated once using a 15 Fr cannula and twice with a 19 Fr arterial cannula. A novel adaptor system that facilitates endovascular access to ECMO circuits was connected, and a 0.035″ Benston wire was placed through the adaptor and guided into the aorta. The cannula was removed over the wire and manual pressure was applied. The MANTA® sheath was inserted over the wire followed by the closure unit and was deployed. The process was repeated at 2 separate sites. A similar experiment was performed in a second swine, but through a median sternotomy to cannulate the ascending aorta.

Results

Good hemostasis was achieved at all cannulation sites. Angiography demonstrated unobstructed flow across all closure sites with no evidence of extravasation.

Conclusions

The data presented here support the use of the MANTA® vascular closure device for the closure of arterial cannulation sites following ECMO decannulation and demonstrates utility of a novel adaptor system for establishing endovascular access in this context.
Flow over a non-uniform sheet with non-uniform stretching (shrinking) and porous velocities
Authors: Alam Aftab , Marwat Dil Nawaz Khan , Asghar Saleem
Published: February 2020

Viscous flow over a porous and stretching (shrinking) surface of an arbitrary shape is investigated in this article. New dimensions of the modeled problem are explored through the existing mathematical analogies in such a way that it generalizes the classical simulations. The latest principles provide a framework for unification, and the consolidated approach modifies the classical formulations. A realistic model is presented with new features in order to explain variety of previous observations on the said problems. As a result, new and upgraded version of the problem is appeared for all such models. A set of new, unusual, and generalized transformations is formed for the velocity components and similarity variables. The modified transformations are equipped with generalized stretching (shrinking), porous velocities, and surface geometry. The boundary layer governing equations are reduced into a set of ordinary differential equations (ODEs) by using the unification procedure and technique. The set of ODEs has two unknown functions f and g. The modeled equations have five different parameters, which help us to reduce the problem into all previous formulations. The problem is solved analytically and numerically. The current simulation and its solutions are also compared with existing models for specific value of the parameters, and excellent agreement is found between the solutions.
Event-triggered communication scheme for stochastic systems in wireless sensor networks
Authors: Xiaoyan Sun , Yi Gao , Quansheng Liu
Published: February 2020

With the development of sensors and network technology, wireless sensor networks are widely used in various scenes. However, in most applications, the energy of the sensor nodes cannot be supplemented. In addition, since the lifetime of the electronic switching element is measured by the number of trigger times, which makes the effective use of energy, extending the working life of the network becomes one of the key factors to be considered. This paper discusses an event-triggered control scheme for stochastic systems. The mechanism determines when the controller sends control data in order to balance system performance and drive frequency. In this paper, the control scheme is deduced by a class of quadratic performance index function. Then, the formula of performance index is designed based on state feedback and output feedback, and the upper bound of performance index is deduced and the conditions in the theorem can be constructed by solving a set of linear matrix inequalities, which can be easily tested with linear matrix inequality algorithms. Finally, a numerical example is given to illustrate the results.
Efficacy and safety of revefenacin for nebulization in patients with chronic obstructive pulmonary disease taking concomitant ICS/LABA or LABA: subgroup analysis from phase III trials
Authors: Sethi Sanjay , Donohue James F. , Ferguson Gary T. , Barnes Chris N. , Crater Glenn D.
Published: February 2020

Background:

Combinations of a long-acting muscarinic receptor antagonist (LAMA), long-acting β-agonist (LABA), and inhaled corticosteroid (ICS) are used for patients with persistent chronic obstructive pulmonary disease (COPD) exacerbations on bronchodilator monotherapy. In this prespecified subgroup analysis, we assessed the efficacy and safety of the LAMA revefenacin in patients with COPD taking concomitant LABA, including ICS/LABA (LABA subgroup).

Methods:

Efficacy data were obtained from two 12-week, replicate, placebo-controlled trials and safety data were pooled from the 12-week and a 52-week tiotropium-controlled trial. Patients received revefenacin 175 µg or placebo in the 12-week or tiotropium 18 µg in the 52-week studies. The efficacy endpoint was least squares (LS) mean change from baseline in trough forced expiratory volume in 1 second (FEV1). Clinical health outcomes were assessed using the St. George’s Respiratory Questionnaire (SGRQ).

Results:

Revefenacin produced similar improvements from baseline in trough FEV1 in the non-LABA and LABA subgroups [placebo-adjusted LS mean change (95% confidence interval) in day 85 trough FEV1, 150.9 (110.3−191.6) ml and 139.2 (82.9−195.5) ml; p < 0.0001 versus placebo]. Similar improvements were observed in SGRQ scores in the non-LABA and LABA subgroups [−3.3 (−5.4 to −1.2) and −3.4 (−6.3 to −0.6)]. Improvements in lung function and health outcomes were observed regardless of airflow obstruction severity. Revefenacin was well tolerated with more adverse events reported in the LABA than the non-LABA subgroup.

Conclusions:

Once daily revefenacin for nebulization can be an effective and well-tolerated treatment for patients who require concomitant use of LABA with or without ICS.

ClinicalTrials.gov identifiers:

NCT02512510, NCT02459080, NCT02518139 The reviews of this paper are available via the supplemental material section.
HR Dynamics in Family-managed Businesses in India
Authors: Ganguly Aniruddha
Published: February 2020

Out of the 100 largest companies listed in India in terms of market cap, more than 50 per cent are family managed. Indian family-managed companies have a distinct organisational culture. Organisational culture shapes and re-shapes people management, influenced by several factors—stage of evolution of the organisation, environmental/economic challenges and owner family culture. The way the owner family conducts itself embodies family governance. Family governance influences corporate governance. Human resource management (HRM) is an essential element of corporate governance. Nature of HRM in family-managed companies is significantly influenced by the way the owner family drives it. Some of the large Indian family-owned companies are consistently high on market cap because they are able to attract and retain the best talent. They can do this consistently because the best talent gets attracted to the best HR practices in an organisation. There is increased awareness of this among Indian owner families and they are now adopting world-class people practices to attract the best talent from the market. Soon we shall have many more Indian family-owned companies indistinguishable from western family-owned companies in terms of people practices.
Developing Culture in Family Business
Authors: Krishnan N.
Published: February 2020

In this article, we have made an attempt to highlight how culture influences and impacts various aspects of running a family business by answering to certain questions such as: How does culture influence the strategic thinking in a family business? Why is that we need to have the right culture aligned with the context? Can multiple cultures coexist in a family business? How do we develop this culture in a family business? Is there a way of assessing what is the predominant culture?
Comparison of pathway and gene-level models for cancer prognosis prediction
Authors: Zheng Xingyu , Amos Christopher I. , Frost H. Robert
Published: February 2020

Background

Cancer prognosis prediction is valuable for patients and clinicians because it allows them to appropriately manage care. A promising direction for improving the performance and interpretation of expression-based predictive models involves the aggregation of gene-level data into biological pathways. While many studies have used pathway-level predictors for cancer survival analysis, a comprehensive comparison of pathway-level and gene-level prognostic models has not been performed. To address this gap, we characterized the performance of penalized Cox proportional hazard models built using either pathway- or gene-level predictors for the cancers profiled in The Cancer Genome Atlas (TCGA) and pathways from the Molecular Signatures Database (MSigDB).

Results

When analyzing TCGA data, we found that pathway-level models are more parsimonious, more robust, more computationally efficient and easier to interpret than gene-level models with similar predictive performance. For example, both pathway-level and gene-level models have an average Cox concordance index of ~ 0.85 for the TCGA glioma cohort, however, the gene-level model has twice as many predictors on average, the predictor composition is less stable across cross-validation folds and estimation takes 40 times as long as compared to the pathway-level model. When the complex correlation structure of the data is broken by permutation, the pathway-level model has greater predictive performance while still retaining superior interpretative power, robustness, parsimony and computational efficiency relative to the gene-level models. For example, the average concordance index of the pathway-level model increases to 0.88 while the gene-level model falls to 0.56 for the TCGA glioma cohort using survival times simulated from uncorrelated gene expression data.

Conclusion

The results of this study show that when the correlations among gene expression values are low, pathway-level analyses can yield better predictive performance, greater interpretative power, more robust models and less computational cost relative to a gene-level model. When correlations among genes are high, a pathway-level analysis provides equivalent predictive power compared to a gene-level analysis while retaining the advantages of interpretability, robustness and computational efficiency.
The canine oral microbiome: variation in bacterial populations across different niches
Authors: Ruparell Avika , Inui Taichi , Staunton Ruth , Wallis Corrin , Deusch Oliver , Holcombe Lucy J.
Published: February 2020

Background

Microbiota from different niches within the canine oral cavity were profiled and compared. Supragingival plaque and stimulated saliva, were collected alongside samples from the buccal and tongue dorsum mucosa, from 14 Labrador retrievers at three timepoints within a 1 month timeframe. The V3-V4 region of the 16S rRNA gene was sequenced via Illumina MiSeq.

Results

Supragingival plaque microbiota had the highest bacterial diversity and the largest number of significant differences in individual taxa when compared to the other oral niches. Stimulated saliva exhibited the highest variability in microbial composition between dogs, yet the lowest bacterial diversity amongst all the niches. Overall, the bacteria of the buccal and tongue dorsum mucosa were most similar.

Conclusions

The bacterial community profiles indicated three discrete oral niches: soft tissue surfaces (buccal and tongue dorsum mucosa), hard tissue surface (supragingival plaque) and saliva. The ability to distinguish the niches by their microbiota signature offers the potential for microbial biomarkers to be identified in each unique niche for diagnostic use.
Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in mice
Authors: Bergmann Berglind , Fei Ying , Jirholt Pernilla , Hu Zhicheng , Bergquist Maria , Ali Abukar , Lindholm Catharina , Ekwall Olov , Churlaud Guillaume , Klatzmann David , Jin Tao , Gjertsson Inger
Published: February 2020

Background

Staphylococcus aureus (S. aureus) arthritis is one of the most detrimental joint diseases known and leads to severe joint destruction within days. We hypothesized that the provision of auxiliary immunoregulation via an expanded compartment of T regulatory cells (Tregs) could dampen detrimental aspects of the host immune response whilst preserving its protective nature. Administration of low-dose interleukin 2 (IL2) preferentially expands Tregs, and is being studied as a treatment choice in several autoimmune conditions. We aimed to evaluate the role of IL2 and Tregs in septic arthritis using a well-established mouse model of haematogenously spred S. aureus arthritis.

Methods

C57BL/6 or NMRI mice we intravenously (iv) injected with a defined dose of S. aureus LS-1 or Newman and the role of IL2 and Tregs were assessed by the following approaches: IL2 was endogenously delivered by intraperitoneal injection of a recombinant adeno-associated virus vector (rAAV) before iv S. aureus inoculation; Tregs were depleted before and during S. aureus arthritis using antiCD25 antibodies; Tregs were adoptively transferred before induction of S. aureus arthritis and finally, recombinant IL2 was used as a treatment starting day 3 after S. aureus injection. Studied outcomes included survival, weight change, bacterial clearance, and joint damage.

Results

Expansion of Tregs induced by IL2 gene therapy prior to disease onset does not compromise host resistance to S. aureus infection, as the increased proportions of Tregs reduced the arthritis severity as well as the systemic inflammatory response, while simultaneously preserving the host’s ability to clear the infection.

Conclusions

Pre-treatment with IL2 gene therapy dampens detrimental immune responses but preserves appropriate host defense, which alleviates S. aureus septic arthritis in a mouse model.
Exclusion of pregnancy in dialysis patients: diagnostic performance of human chorionic gonadotropin
Authors: Haninger-Vacariu Natalja , Herkner Harald , Lorenz Matthias , Säemann Marcus , Vychytil Andreas , Jansen Martin , Marculescu Rodrig , Kramar Reinhard , Sunder-Plassmann Gere , Schmidt Alice
Published: February 2020

Background

A positive pregnancy test in acute or chronically ill patients has implications for the use of potentially mutagenic or teratogenic products in urgent medical therapies such as the use of chemotherapies or therapies with immunosuppressants, for anesthesia, and for time-sensitive indications like urgent surgery or organ Transplantation.

Despite a lack of evidence, it is currently believed that human chorionic gonadotropin serum concentrations are always elevated in female dialysis patients even without pregnancy. It is also believed that human chorionic gonadotropin cannot be used to confirm or exclude pregnancy.

Methods

Human chorionic gonadotropin was examined in female dialysis patients (18–50 years of age), and was classified as positive above 5 mlU/ml. In addition, fertility status was determined. For an enhanced index test, the cut-off of 5 mIU/ml was used for potentially fertile patients and 14 mIU/ml for infertile patients to calculate diagnostic test accuracy. The ideal cut-off for human chorionic gonadotropin was estimated using Liu’s method with bootstrapped 95% confidence intervals. Predictors of human chorionic gonadotropin increase were analyzed using multivariable linear regression.

Results

Among 71 women, two (2.8%) were pregnant, 46 (64.8%) potentially fertile, and 23 (32.4%) infertile. We observed human chorionic gonadotropin concentrations > 5 mIU/ml in 10 patients, which had a sensitivity of 100% (95% confidence interval: 100 to 100), a specificity of 86% (95% confidence interval: 77 to 94), a positive predictive value of 17% (95% confidence interval: 8 to 25) and a negative predictive value of 100% (95% confidence interval: 100 to 100) for the diagnosis of pregnancy. Using a cut-off > 14 mIU/ml for infertile patients or the exclusion of infertile patients increased specificity to 93% or 98%, respectively. The ideal cut-off was 25 mIU/ml (95% confidence interval: 17 to 33). Pregnancy and potential fertility, but not age, were independent predictors of human chorionic gonadotropin.

Conclusion

Human chorionic gonadotropin is elevated > 5mIU/ml in 14.5% of non-pregnant dialysis patients of child-bearing age. In potentially fertile women, this cut-off can be used to exclude pregnancy. In case of an unknown fertility status, the ideal human chorionic gonadotropin cut-off was 25 mIU/ml.
Karyomegalic interstitial nephritis with a novel FAN1 gene mutation and concurrent ALECT2 amyloidosis
Authors: Law Steven , Gillmore Julian , Gilbertson Janet A. , Bass Paul , Salama Alan D.
Published: February 2020

Background

Karyomegalic interstitial nephritis (KIN) is a rare hereditary cause of chronic kidney disease. It typically causes progressive renal impairment with haemoproteinuria requiring renal replacement therapy before 50 years of age. It has been associated with mutations in the Fanconi anaemia-associated nuclease 1 (FAN1) gene and has an autosomal recessive pattern of inheritance. Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is the third most common cause of amyloid nephropathy presenting with chronic kidney disease and variable proteinuria. We report a novel mutation in the FAN1 gene causing KIN and to our knowledge, the first case of concurrent KIN and ALECT.

Case presentation

We describe the case of 44 year old Pakistani woman, presenting with stage four non-proteinuric chronic kidney disease, and a brother on dialysis. Renal biopsy demonstrated KIN and concurrent ALECT2. Genetic sequencing identified a novel FAN1 mutation as the cause of her KIN and she is being managed conservatively for chronic kidney disease. Her brother also had KIN with no evidence of amyloidosis and is being worked up for kidney transplantation.

Conclusion

This case highlights two rare causes of chronic kidney disease considered underdiagnosed in the wider population due to their lack of proteinuria, and may contribute to the cohort of patients reaching end stage renal disease without a renal biopsy. We report a novel mutation of the FAN1 gene causing KIN, and report the first case of concurrent KIN and ALECT2. This case highlights the importance of renal biopsy in chronic kidney disease of unclear aetiology which has resulted in a diagnosis with implications for kidney transplantation and family planning.
The burden of unrecognised chronic kidney disease in patients with type 2 diabetes at a county hospital clinic in Kenya: implications to care and need for screening
Authors: Otieno Frederick C. F. , Ogola Elijah N. , Kimando M. W. , Mutai Kenn
Published: February 2020

Background

Chronic Kidney Disease (CKD) in patients with type 2 diabetes enhances the cardiovascular risk profiles and disease, and is a strong predictor of progression to end-stage kidney disease. Early diagnosis is encouraged for referral to specialist kidney care to initiate active management that would optimize outcomes including forestalling progression to end-stage kidney disease.

This study was conducted in a regional referral public health facility in Central Kenya with a high prevalence of type 2 diabetes. It was aimed at finding out the burden of undiagnosed chronic kidney disease in their clinic of ambulatory patients with type 2 diabetes who dwell mainly in the rural area.

Methods

A cross-sectional study was conducted at the out-patient of Nyeri County hospital. A total of 385 patients were enrolled over 5 months. Informed consent was obtained and clinical evaluation was done, a spot sample of urine obtained for albuminuria and venous blood drawn for HbA1c, Lipids and serum creatinine. Estimated GFR (eGFR) was calculated using the Cockroft-Gault equation. Chronic kidney disease (CKD) was classified on KDIGO scale. Albuminuria was reported as either positive or negative. Descriptive statistics for data summary and regression analysis were employed on SPSS v23.

Results

A total of 385 participants were included in the study, 252 (65.5%) were females. There were 39.0% (95%CI 34.3–44.2) patients in CKD/KDIGO stages 3, 4 and 5 and 32.7% (95%CI, 27.8–37.4) had Albuminuria. The risk factors that were significantly associated with chronic kidney disease/KDIGO stages 3, 4 and 5 were: age > 50 years, long duration with diabetes > 5 years and hypertension. Employment and paradoxically, obesity reduced the odds of having CKD, probably as markers of better socio-economic status.

Conclusion

Unrecognized CKD of KDIGO stages 3,4 and 5 occurred in over 30 % of the study patients. The risk factors of hypertension, age above 50, long duration of diabetes should help identify those at high risk of developing CKD, for screening and linkage to care. They are at high risk of progression to end-stage kidney disease and cardiovascular events. The imperative of screening for chronic kidney disease is availing care in publicly-funded hospitals.
Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis
Authors: Qu Nanfang , Qin Sanyu , Zhang Xuemei , Bo Xiaotong , Liu Zhengchun , Tan Chao , Wen Guiqiong , Jiang Haixing
Published: February 2020

Background

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N6-methyladenosine (m6A) RNA methylation is dynamically regulated by m6A RNA methylation modulators (“writer,” “eraser,” and “reader” proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m6A RNA methylation modulators and HCC.

Methods

First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m6A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m6A RNA methylation modulators that affected OS in TCGA and ICGC analyses.

Results

We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m6A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS.

Conclusions

In summary, m6A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.