bluuebunny/crossref_metadata_2025 huggingface dataset:
‘They are inconveniencing us’ - exploring how gaps in patient education and patient centred approaches interfere with TB treatment adherence: perspectives from patients and clinicians in the Free State Province, South Africa
Authors: Moodley N. , Saimen A. , Zakhura N. , Motau D. , Setswe G. , Charalambous S. , Chetty-Makkan C. M.
Published: April 2020

Background

Tuberculosis (TB) treatment loss to follow up (LTFU) plays an important contributory role to the staggering TB epidemic in South Africa. Reasons for treatment interruption are poorly understood. Treatment interruption appears to be the culmination of poor health literacy of patients and inadequate health education provided by clinicians. We explored clinician and patient perspectives of the gaps in TB messaging that influence TB treatment LTFU.

Methods

We conducted semi-structured in-depth interviews between January and May 2018 with a sample of 15 clinicians managing TB and 7 patients identified as LTFU in public clinics in the Free State Province, South Africa. Thematic analysis using a mixed deductive/inductive thematic approach was used.

Results

Limited occupational opportunities, fear of disclosure and stigmatization all contributed to treatment LTFU. Patients felt that the TB messaging received was inadequate. Many of the clinicians interviewed felt that improving patient’s TB knowledge would reinforce adherence to treatment and thus focused on sharing information on treatment completion, side effects and infection control. However, the inability of clinicians to establish rapport with patients or to identify social support challenged TB treatment adherence by patients. Clinicians perceived this as patients not following their instructions despite what they considered lengthy TB education. Having said this, clinicians concurred that their medical management of TB lacked the psycho-social dimension to treat a social disease of this magnitude.

Conclusions

Limited occupational opportunities, fear of disclosure and stigmatization all contributed to treatment LTFU. Clinicians concurred that poor patient understanding of TB and that biomedical management lacking a psycho-social dimension further exacerbated the poor treatment outcome. TB remains a social disease, the successful management of which hinges on patient-centred care.
Young Aboriginal people’s engagement with STI testing in the Northern Territory, Australia
Authors: Bell Stephen , Aggleton Peter , Ward James , Murray Walbira , Silver Bronwyn , Lockyer Andrew , Ferguson Tellisa , Fairley Christopher K. , Whiley David , Ryder Nathan , Donovan Basil , Guy Rebecca , Kaldor John , Maher Lisa
Published: April 2020

Background

Australian surveillance data document higher rates of sexually transmissible infections (STIs) among young Aboriginal people (15–29 years) in remote settings than non-Aboriginal young people. Epidemiological data indicate a substantial number of young Aboriginal people do not test for STIs. Rigorous qualitative research can enhance understanding of these findings. This paper documents socio-ecological factors influencing young Aboriginal people’s engagement with clinic-based STI testing in two remote settings in the Northern Territory, Australia.

Methods

In-depth interviews with 35 young Aboriginal men and women aged 16–21 years; thematic analysis examining their perceptions and personal experiences of access to clinic-based STI testing.

Results

Findings reveal individual, social and health service level influences on willingness to undertake clinic-based STI testing. Individual level barriers included limited knowledge about asymptomatic STIs, attitudinal barriers against testing for symptomatic STIs, and lack of skills to communicate about STIs with health service staff. Social influences both promoted and inhibited STI testing. In setting 1, local social networks enabled intergenerational learning about sexual health and facilitated accompanied visits to health clinics for young women. In setting 2, however, social connectedness inhibited access to STI testing services. Being seen at clinics was perceived to lead to stigmatisation among peers and fear of reputational damage due to STI-related rumours. Modalities of health service provision both enhanced and inhibited STI testing. In setting 1, outreach strategies by male health workers provided young Aboriginal men with opportunities to learn about sexual health, initiate trusting relationships with clinic staff, and gain access to clinics. In setting 2, barriers were created by the location and visibility of the clinic, appointment procedures, waiting rooms and waiting times. Where inhibitive factors at the individual, social and health service levels exist, young Aboriginal people reported more limited access to STI testing.

Conclusions

This is the first socio-ecological analysis of factors influencing young Aboriginal people’s willingness to undertake testing for STIs within clinics in Australia. Strategies to improve uptake of STI testing must tackle the overlapping social and health service factors that discourage young people from seeking sexual health support. Much can be learned from young people’s lived sexual health experiences and family- and community-based health promotion practices.
Process evaluation of a whole-of-community systems approach to address childhood obesity in western Victoria, Australia
Authors: Jenkins Ebony , Lowe Janette , Allender Steven , Bolton Kristy A.
Published: April 2020

Background

SEA Change Portland is a systems-based approach implemented in Portland, Victoria that utilises local community resources to sustainably prevent and reduce the prevalence of childhood obesity. Action is implemented by community-led task teams with differing priority areas, and supported by a steering committee representative of four collaborating organisations. This study examines the SEA Change Portland process to identify significant events, enablers and barriers of its development and implementation to date as reported by key stakeholders involved in implementation during the first 12 months.

Methods

Semi-structured interviews were conducted with eight steering group members and three community task team members. Data was collected utilising open ended interview questions to gather in-depth information regarding program implementation, and the individual attitudes, beliefs and experiences of key stakeholders.

Results

Data were analysed under three key themes: collective impact, systems thinking and asset based community development (ABCD). Participants gave perceptions of significant events; factors positively and negatively affecting the process; reasons for becoming involved in the process; perceived efficacy of task teams, principles of diversity and areas of concern. Themes emerged from participant responses allowing were categorisation of their responses into four key process stages: initial lead up; process development; establishing community ownership of the obesity system; and community action.

Conclusion

Collective impact was a crucial element in applying the systems thinking. Strong and equitable relationships between steering organisations and topic experts provided the initiative with a sustainable foundation, and ABCD promotes community ownership and future sustainability. Understanding the process of implementing a new whole-of-community systems approach to childhood obesity prevention such as SEA Change Portland has provided vital knowledge for other communities regarding enablers and barriers of this promising approach.
NTP42, a novel antagonist of the thromboxane receptor, attenuates experimentally induced pulmonary arterial hypertension
Authors: Mulvaney Eamon P. , Reid Helen M. , Bialesova Lucia , Bouchard Annie , Salvail Dany , Kinsella B. Therese
Published: April 2020

Background

NTP42is a novel antagonist of the thromboxane prostanoid receptor (TP), currently in development for the treatment of pulmonary arterial hypertension (PAH). PAH is a devastating disease with multiple pathophysiological hallmarks including excessive pulmonary vasoconstriction, vascular remodelling, inflammation, fibrosis, in situ thrombosis and right ventricular hypertrophy. Signalling through the TP, thromboxane (TX) A2is a potent vasoconstrictor and mediator of platelet aggregation. It is also a pro-mitogenic, pro-inflammatory and pro-fibrotic agent. Moreover, the TP also mediates the adverse actions of the isoprostane 8-iso-prostaglandin F2α, a free-radical-derived product of arachidonic acid produced in abundance during oxidative injury. Mechanistically, TP antagonists should treat most of the hallmarks of PAH, including inhibiting the excessive vasoconstriction and pulmonary artery remodelling, in situ thrombosis, inflammation and fibrosis. This study aimed to investigate the efficacy ofNTP42in the monocrotaline (MCT)-induced PAH rat model, alongside current standard-of-care drugs.

Methods

PAH was induced by subcutaneous injection of 60 mg/kg MCT in male Wistar–Kyoto rats. Animals were assigned into groups: 1. ‘No MCT’; 2. ‘MCT Only’; 3. MCT + NTP42(0.25 mg/kg BID); 4. MCT + Sildenafil (50 mg/kg BID), and 5. MCT + Selexipag (1 mg/kg BID), where 28-day drug treatment was initiated within 24 h post-MCT.

Results

From haemodynamic assessments, NTP42reduced the MCT-induced PAH, including mean pulmonary arterial pressure (mPAP) and right systolic ventricular pressure (RSVP), being at least comparable to the standard-of-care drugs Sildenafil or Selexipag in bringing about these effects. Moreover,NTP42was superior to Sildenafil and Selexipag in significantly reducing pulmonary vascular remodelling, inflammatory mast cell infiltration and fibrosis in MCT-treated animals.

Conclusions

These findings suggest thatNTP42and antagonism of the TP signalling pathway have a relevant role in alleviating the pathophysiology of PAH, representing a novel therapeutic target with marked benefits over existing standard-of-care therapies.
Amongst patients taking biologic therapies for axial spondyloarthritis, which factors are associated with work non-participation?
Authors: Nadin Tom , Wallis Dinny , Holroyd Christopher R. , D’Angelo Stefania , Walker-Bone Karen , Edwards Christopher J.
Published: April 2020

Background

Axial spondyloarthritis (axSpA) frequently presents during working age and therefore impacts work participation. Biologic therapies have demonstrated a positive impact on work-related outcomes in clinical trials but real world data are limited. Therefore, we investigated the prevalence and predictors of work impairment and disability among axSpA patients attending a biologic therapy clinic.

Methods

This was a single-centre, cross-sectional study of patients with axSpA treated with biologic therapy. Work participation was assessed with the Work Productivity and Activity Impairment (WPAI) Questionnaire. Work outcomes (presenteeism, absenteeism, health-related job loss) were compared for gender, time since diagnosis, smoking status and disease outcome measures.

Results

Data were available for 165 patients (mean age 47.6 years, 75% male, 21% current smokers). Mean time since diagnosis was 15.5 years and mean duration of biologic therapy 4.7 years; 19/165 (11.5%) were on a tapered-dose regimen. Occupational data were available for 144 patients amongst whom 101 (70.1%) were either currently employed or in full time education. Of those eligible to work, 17/118 (14.4%) reported inability to work due to their axSpA. Amongst those in employment, 10.8% reported absenteeism due to axSpA in the week prior to their clinic visit (mean hours missed = 13). The mean work productivity impairment was 23%. Higher disease activity (BASDAI) and markers of global health, quality of life and pain, (BAS-G, ASQoL and spinal pain VAS) were associated with axSpA related job loss, absenteeism and presenteeism.

Conclusions

In this group of axSpA patients on biologic therapy (mean age 47.6 years), almost 1 in 6 (14.4%) reported axSpA related job loss. Poor work outcomes: axSpA-related work disability, absenteeism and presenteeism were associated with poorer scores for patient-reported disease outcome measures. Strategies for enhancing work productivity should be directed towards those patients at risk of poor work outcomes. More data are needed including details of the types of work that are most difficult with axSpA.
Optimal location of subtrochanteric osteotomy in total hip arthroplasty for crowe type IV developmental dysplasia of hip
Authors: Huang Zhe-Yu , Liu Hua , Li Ming , Ling Jing , Zhang Jun-Hui , Zeng Zhi-Min
Published: April 2020

Background

When reconstructing a hip with developmental dysplasia and high dislocation, sub-trochanteric shortening osteotomy is typically needed for placing the acetabular component in the appropriate anatomical position. However, the procedure can result in complications such as non-union of the osteotomy. We evaluated the contact area and the coincidence rate between the proximal and distal fragments at different femoral osteotomy levels and lengths. We then determined the optimal location of subtrochanteric femoral shortening transverse osteotomy in patients with unilateral Crowe type IV developmental dysplasia of the hip (DDH). The consistency between the proximal and distal segments was assessed as a possible predictive indicator of the union at the osteotomy site.

Methods

We retrospectively reviewed 57 patients with unilateral Crowe type IV DDH who underwent X-ray imaging of both hip joints. We labelled the inner and outer diameters of the circular ring as N (mm) and M (mm), respectively. We defined the overlapped area between the proximal and distal ring as contact area S (mm2), and the ratio of contact area to distal ring area as coincidence rate R.

Results

N varied from 9.8–15.2 mm and M varied from 20.7–24 mm, both demonstrated a decreasing trend in the proximal to distal direction. At osteotomy lengths ranging from 0.5–2 cm, there were no differences in S between the different levels of osteotomy in each group. At osteotomy lengths ≤2.5 cm, a significant higher coincidence rate was noted from 2 cm below the lesser trochanter to other positions below the level. At osteotomy lengths from 3 to 5.5 cm, a significantly higher coincidence rate was observed from the level of 1.5 cm below the lesser trochanter to other positions below the level.

Conclusions

Our findings suggest that femoral shortening transverse osteotomy at the optimal subtrochanteric level can predictably increase the contact area and coincidence rate, which may contribute to the union at the osteotomy site. Considering the stability of the prostheses, it appears appropriate that osteotomy location should be shifted slightly distally.

Trial registration

Retrospectively registered.
Intrahepatic cholangiocarcinoma – influence of resection margin and tumor distance to the liver capsule on survival
Authors: Bartsch Fabian , Baumgart Janine , Hoppe-Lotichius Maria , Straub Beate K. , Heinrich Stefan , Lang Hauke
Published: April 2020

Background

Intrahepatic cholangiocarcinoma (ICC) is often diagnosed in advanced stage. Aim of this study was to analyse the influence of resection margins and tumor distance to the liver capsule on survival and recurrence in a single center with a high number of extended resections.

Methods

From January 2008 to June 2018 data of all patients with ICC were collected and further analysed with Kaplan Meier Model, Cox regression or Chi2 test for categorical data.

Results

Out of 210 included patients 150 underwent curative intended resection (71.4%). Most patients required extended resections (n = 77; 51.3%). R0-resection was achieved in 131 patients (87.3%) with minimal distances to the resection margin > 1 cm in 22, 0.5-1 cm in 11, 0.1–0.5 cm in 49 patients, and <  0.1 cm in 49 patients. Overall survival (OS) for margins > 0.5 cm compared to 0.5–0.1 cm or R1 was better, but without reaching significance. All three groups had significantly better OS compared to the irresectable group. Recurrence-free survival (RFS) was also better in patients with a margin > 0.5 cm than in the < 0.5–0.1 cm or the R1-group, but even without reaching significance. Different distance to the liver capsule significantly affected OS, but not RFS.

Conclusions

Wide resection margins (> 0.5 cm) should be targeted but did not show significantly better OS or RFS in a cohort with a high percentage of extended resections (> 50%). Wide margins, narrow margins and even R1 resections showed a significant benefit over the irresectable group. Therefore, extended resections should be performed, even if only narrow margins can be achieved.
The reliability of surgeons to avoid traumatic insertion of dental implants into high-risk regions: a panoramic radiograph study
Authors: Jamil Firas A. , Mohammed Jamal A. , Hasan Thair A. , Rzoqi Mohammed G.
Published: April 2020

Background

The posterior regions of the jaws usually represent a significant risk for implant surgery. A non-valid assessment of the available bone height may lead to either perforation of the maxillary sinus floor or encroachment of the inferior alveolar nerve and consequently to implant failure. This study aimed to evaluate the reliability of surgeon’s decision in appraising the appropriate implant length, in respect to vital anatomical structures, using panoramic radiographs.

Methods

Only implants that are inserted in relation to the maxillary sinus (MS) or the mandibular canal (MC) were enrolled (first premolars [1P], second premolars [2P], first molars [1M], and second molars [2M]). All preoperative panoramic radiographs were evaluated under standard conditions. The postoperative estimation (under/over) was determined depending on the available bone height (ABH) measured from the apical end of the implant to the floor of the MS and the roof of the MC using cone beam computed tomography (CBCT). Any complication or side effect that associated with overestimated implants insertion was recorded.

Results

The study sample included 73 patients (predominantly females) who had consecutively received 148 implants, of which 68 were inserted in the posterior maxilla and 80 in the posterior mandible. Underestimation was recorded in 93.2% of the measurements. The remaining bone height after implants insertion was < 2 mm in the majority of underestimated cases (73.9%); they were significantly (P < 0.01) more than sites with remaining bone ≥ 2 mm (26.1%). In the posterior mandible, overestimation was significantly higher than posterior maxilla. Five cases with transient paresthesia were reported in the mandibular overestimated implants.

Conclusions

This study specified that surgeon’s choice of implants length, based on panoramic radiographs, was reliable regarding the incapability to insert implants with further length in the majority of underestimated cases, the low percent of overestimated measurements, and the minor associated complications.
Men’s view on participation in decisions about prostate-specific antigen (PSA) screening: patient and public involvement in development of a survey
Authors: Birkeland Søren , Pedersen Susanne S. , Haakonsson Anders K. , Barry Michael J. , Rottmann Nina
Published: April 2020

Background

Prostate-Specific Antigen (PSA) screening for early detection of prostate cancer (PCa) may prevent some cancer deaths, but also may miss some cancers or lead to unnecessary and potentially harmful treatment. Therefore, involving patients in decision-making about PSA screening is recommended. However, we know little about the attitude of men regarding participation in decisions about PSA screening and how to assess such attitudes. The purpose of this paper is to describe patient and public participation in the development of a national, web-based case vignette survey for studying men’s view on participation in decision-making about PSA screening.

Methods

The project group developed a first draft plan for the survey, its vignettes and choice of measurements. This included multiple vignette variants representing various levels of patient participation in decision-making about PSA screening with different outcomes. Additionally, it included questions on respondents’ satisfaction with imagined courses of health care, their propensity to initiate a malpractice complaint, their own health care experiences, socio-demography, personality, and preferences for control regarding health care decision-making. Following feedback from a workshop with academic peers on the draft plan, a group of 30 adult men was engaged to help develop case vignette versions and questionnaire items by providing feedback on structure, comprehension, response patterns, and time required to complete the survey. Furthermore, a panel of three patients with PCa experience was assembled to assist development through a separate review-and-feedback process.

Results

Based on reviews of survey drafts, the large group made further suggestions about construction of the survey (e.g. clarification and modification of case vignette versions, deletion of items and adjustment of wording, instructions to guide respondents, replacement of technical terms, and optimization of sequence of survey elements). The patient panel ensured fine-tuning of vignette versions and questionnaire items and helped review the internet version of the survey.

Conclusions

Patient and public involvement during various phases of the survey development helped modify and refine survey structure and content. The survey exemplifies a way to measure health care users’ satisfaction with imagined courses of health care and wish to complain, taking into account their characteristics.
Developing senior hospital managers: does ‘one size fit all’? – evidence from the evolving Chinese health system
Authors: Liang Zhanming , Howard Peter , Wang Jian , Xu Min , Zhao Mei
Published: April 2020

Background

To improve the effectiveness and efficiency of health service provision in China, the National Health Commission has emphasised that training of all health service managers is essential. However, the implementation of that policy has proven challenging for various reasons, one of which is the lack of understanding of the competency requirements and gaps. The aims of the study were to develop an understanding of the characteristics and training experience of hospital managers in one major Chinese city, explore the difficulties they experience and relate them to their perceived importance of management competencies and the perceived level of their management competency.

Methods

A cross-sectional, descriptive study with a three-component survey including the use of a validated management competency assessment tool was conducted with three senior executive groups (n = 498) from three categories of hospital in Jinan, Shandong Province, China.

Results

The survey confirmed that formal and informal management training amongst participants before commencing their management positions was inadequate. The core competencies identified in the Australia context were applicable to the management roles in Chinese hospitals. In addition, the senior executives had low levels of confidence in their management competence. Furthermore, the data showed significant differences between hospital categories and management levels in terms of their commitment to formal and informal training and self-perceived management competence.

Conclusions

The study suggests that management training and support should be provided using a systematic approach with specific consideration to hospital types and management levels and positions. Such an approach should include clear competency requirements to guide management position recruitment and performance management.
Use of meat juice and blood serum with a miniaturised protein microarray assay to develop a multi-parameter IgG screening test with high sample throughput potential for slaughtering pigs
Authors: Loreck Katharina , Mitrenga Sylvia , Heinze Regina , Ehricht Ralf , Engemann Claudia , Lueken Caroline , Ploetz Madeleine , Greiner Matthias , Meemken Diana
Published: April 2020

Background

Serological screening of pig herds at the abattoir is considered a potential tool to improve meat inspection procedures and herd health management. Therefore, we previously reported the feasibility of a miniaturised protein microarray as a new serological IgG screening test for zoonotic agents and production diseases in pigs. The present study investigates whether the protein microarray-based assay is applicable for high sample throughput using either blood serum or meat juice.

Material and methods

Microarrays with 12 different antigens were produced by Abbott (formerly Alere Technologies GmbH) Jena, Germany in a previously offered ‘ArrayTube’ platform and in an ‘ArrayStrip’ platform for large-scale use. A test protocol for the use of meat juice on both microarray platforms was developed. Agreement between serum and meat juice was analysed with 88 paired samples from three German abattoirs. Serum was diluted 1:50 and meat juice 1:2. ELISA results for all tested antigens from a preceding study were used as reference test to perform Receiver Operating Characteristic analysis for both test specimens on both microarray platforms.

Results

High area under curve values (AUC > 0.7) were calculated for the analysis of T. gondii (0.87), Y. enterocolitica (0.97), Mycoplasma hyopneumoniae (0.84) and Actinobacillus pleuropneumoniae (0.71) with serum as the test specimen and for T. gondii (0.99), Y. enterocolitica (0.94), PRRSV (0.88), A. pleuropneumoniae (0.78) and Salmonella spp. (0.72) with meat juice as the test specimen on the ArrayStrip platform. Cohens kappa values of 0.92 for T. gondii and 0.82 for Y. enterocolitica were obtained for the comparison between serum and meat juice. When applying the new method in two further laboratories, kappa values between 0.63 and 0.94 were achieved between the laboratories for these two pathogens.

Conclusion

Further development of a miniaturised pig-specific IgG protein microarray assay showed that meat juice can be used on microarray platforms. Two out of twelve tested antigens (T. gondii, Y. enterocolitica) showed high test accuracy on the ArrayTube and the ArrayStrip platform with both sample materials.
Comprehensive primary health care and non-communicable diseases management: a case study of El Salvador
Authors: Jimenez Carrillo Marta , León García Montserrat , Vidal Nicole , Bermúdez Keven , De Vos Pol
Published: April 2020

Background

One of today’s greatest challenges in public health worldwide - and especially its key management from Primary Health Care (PHC) - is the growing burden of non-communicable diseases (NCDs). In El Salvador, since 2009 the Minister of Health (MoH) has scaled up a national public health system based on a comprehensive PHC approach. A national multi-sectorial strategic plan for a comprehensive approach to NCDs has also been developed. This analysis explores stakeholders’ perceptions related to the management of NCDs in PHC and, in particular, the role of social participation.

Methods

A case-study was developed consisting of semi structured interviews and official document reviews. Semi-structured interviews were developed with chronic patients (14) and PHC professionals working in different levels within PHC (12). Purposive sampling was used to recruit participants. A non-pure, deductive approach was implemented for coding. After grouping codes into potential themes, a thematic framework was elaborated through a reflexive approach and the triangulation of the data. The research was conducted between March and August of 2018 in three different departments of El Salvador.

Results

The structure and the functioning of the Salvadoran PHC system and its intersectoral approach is firstly described. The interdisciplinary PHC-team brings holistic health care closer to the communities in which health promoters play a key role. The findings reflect the generally positive perception of the PHC system in terms of accessibility, quality and continuity of care by chronic patients. Community engagement and the National Health Forum are ensuring accountability through social controllership mechanisms. However, certain challenges were also noted during the interviews related to the shortage of medication and workforce; coordination between the levels of care and the importance of prevention and health promotion programmes for NCDs.

Conclusions

The Salvadoran PHC and its comprehensive approach to NCDs with an emphasis on intersectoral participation has been positively perceived by the range of stakeholders interviewed. Social engagement and the NHF works as a driving force to ensure accountability as well as in the promotion of a preventive culture. The challenges identified provide keys to amplify knowledge for addressing inequalities in health by strengthening PHC and its NCDs management.
Well-being profiles in adolescence: psychometric properties and latent profile analysis of the mental health continuum model – a methodological study
Authors: Reinhardt Melinda , Horváth Zsolt , Morgan Antony , Kökönyei Gyöngyi
Published: April 2020

Background

The Adolescent Mental Health Continuum Short Form (MHC-SF) is a psychometrically valid tool to evaluate the domains of subjective well-being, but there is a lack of investigations which could distinguish subgroups with distinct subjective well-being profiles based on this measurement. Therefore, after testing the competing measurement models of the MHC-SF, our main aim was to identify subjective well-being profiles in a large adolescent sample.

Methods

On a representative Hungarian adolescent sample (N = 1572; 51% girl; mean age was 15.39, SD = 2.26) confirmatory factor analyses (CFA) and exploratory structural equation modeling (ESEM) were used to test the factor stucture of the Adolescent MHC-SF. In addition, gender invariance of the best fitting model was also tested. Latent Profile Analyses (LPA) were conducted to reveal distinct subgroups and these profiles were then compared.

Results

Results support the bifactor model of MHC-SF: the general and specific well-being factors which were invariant across gender. LPA yielded four subgroups, three of them have been theoretically hypothesized in previous works (i.e. flourishing, moderate mental health, languishing), but an emotionally vulnerable subgroup also emerged. Compared to the languishing group, this new subgroup demonstrated higher scores on prosocial behaviour, but had comparable level of loneliness and internalizing symptoms.

Conclusions

Our results suggest that the MHC-SF is a reliable and valid instrument for assessing overall well-being and its components. In addition, the identification of young people to be at risk for low mental health may help us to tailor mental health promotion programs to their special needs.
Association between pubertal development stages and body adiposity in children and adolescents
Authors: Adami Fernando , Benedet Jucemar , Takahashi Livia Akemi Ramos , da Silva Lopes Adair , da Silva Paiva Laércio , de Vasconcelos Francisco de Assis Guedes
Published: April 2020

Background

The study aimed to analyze the association between pubertal development stages and adiposity in children and adolescents.

Methods

Cross-sectional study conducted in 2007 in Florianópolis, Brazil, with 2339 schoolchildren 32 aged 8 to 14 years old (1107 males). The outcome (adiposity) was evaluated using Z score and 33 percentilee values > = 85 of four skinfolds (triceps, subscapular, suprailiac and calf) and waist 34 circumference. Total body adiposity (Z score of the sum of skinfolds), central adiposity (Z score 35 of waist circumference) and peripheral adiposity (Z scores of triceps and calf skinfolds) were 36 estimated. Pubertal development stages was self-assessed according to Tanner stages of development. Thirty-seven Children and adolescents were classified according to tertiles of age for each pubertal development stages 38 stage - early, normal and late. Statistical analysis was performed using univariate and 39 multivariate Poisson regression models.

Results

Children and adolescent from both sexes with early pubertal development stages presented higher prevalence of central adiposity (waist circumference), with adjusted prevalence ratio (CI 95%) of 2.21 (1.12; 4.35) for males and 2.18 (1.04; 4.57) for females (reference group: normal pubertal development stages). Among females, there was a reduction in the prevalence of excess adiposity with decreased occurrence of early pubertal development stages. There was a strong relationship between adiposity and pubertal development stages.

Conclusions

Excess adiposity was higher in both sexes for those with early pubertal development stages.
CT imaging changes of corona virus disease 2019(COVID-19): a multi-center study in Southwest China
Authors: Li Xiaoming , Zeng Wenbing , Li Xiang , Chen Haonan , Shi Linping , Li Xinghui , Xiang Hongnian , Cao Yang , Chen Hui , Liu Chen , Wang Jian
Published: April 2020

Background

Since the first case of a coronavirus disease 2019 (COVID-19) infection pneumonia was detected in Wuhan, China, a series of confirmed cases of the COVID-19 were found in Southwest China. The aim of this study was to describe the imaging manifestations of hospitalized patients with confirmed COVID-19 infection in southwest China.

Methods

In this retrospective study, data were collected from 131 patients with confirmed coronavirus disease 2019 (COVID-19) from 3 Chinese hospitals. Their common clinical manifestations, as well as characteristics and evolvement features of chest CT images, were analyzed.

Results

A total of 100 (76%) patients had a history of close contact with people living in Wuhan, Hubei. The clinical manifestations of COVID-19 included cough, fever. Most of the lesions identified in chest CT images were multiple lesions of bilateral lungs, lesions were more localized in the peripheral lung, 109 (83%) patients had more than two lobes involved, 20 (15%) patients presented with patchy ground glass opacities, patchy ground glass opacities and consolidation of lesions co-existing in 61 (47%) cases. Complications such as pleural thickening, hydrothorax, pericardial effusion, and enlarged mediastinal lymph nodes were detected but only in rare cases. For the follow-up chest CT examinations (91 cases), We found 66 (73%) cases changed very quickly, with an average of 3.5 days, 25 cases (27%) presented absorbed lesions, progression was observed in 41 cases (46%), 25 (27%) cases showed no significant changes.

Conclusion

Chest CT plays an important role in diagnosing COVID-19. The imaging pattern of multifocal peripheral ground glass or mixed consolidation is highly suspicious of COVID-19, that can quickly change over a short period of time.
Preparation of uniformly labelled 13C- and 15N-plants using customised growth chambers
Authors: Ćeranić Asja , Doppler Maria , Büschl Christoph , Parich Alexandra , Xu Kangkang , Koutnik Andrea , Bürstmayr Hermann , Lemmens Marc , Schuhmacher Rainer
Published: April 2020

Background

Stable isotopically labelled organisms have found wide application in life science research including plant physiology, plant stress and defense as well as metabolism related sciences. Therefore, the reproducible production of plant material enriched with stable isotopes such as13C and15N is of considerable interest. A high degree of enrichment (> 96 atom %) with a uniformly distributed isotope (global labelling) is accomplished by a continuous substrate supply during plant growth/cultivation. In the case of plants,13C-labelling can be achieved by growth in13CO2(g)atmosphere while global15N-labelling needs15N- containing salts in the watering/nutrient solution. Here, we present a method for the preparation of13C and15N-labelled plants by the use of closed growth chambers and hydroponic nutrient supply. The method is exemplified with durum wheat.

Results

In total, 330 g of globally13C- and 295 g of15N-labelledTriticum durumwheat was produced during 87 cultivation days. For this, a total of 3.88 mol of13CO2(g)and 58 mmol of15N were consumed. The degree of enrichment was determined by LC-HRMS and ranged between 96 and 98 atom % for13C and 95–99 atom % for15N, respectively. Additionally, the isotopically labelled plant extracts were successfully used for metabolome-wide internal standardisation of nativeT.durumplants. Application of an isotope-assisted LC-HRMS workflow enabled the detection of 652 truly wheat-derived metabolites out of which 143 contain N.

Conclusion

A reproducible cultivation which makes use of climate chambers and hydroponics was successfully adapted to produce highly enriched, uniformly13C- and15N-labelled wheat. The obtained plant material is suitable to be used in all kinds of isotope-assisted research. The described technical equipment and protocol can easily be applied to other plants to produce13C-enriched biological samples when the necessary specific adaptations e.g. temperature and light regime, as well as nutrient supply are considered. Additionally, the15N-labelling method can also be carried out under regular glasshouse conditions without the need for customised atmosphere.
Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins
Authors: Van Nostrand Eric L. , Pratt Gabriel A. , Yee Brian A. , Wheeler Emily C. , Blue Steven M. , Mueller Jasmine , Park Samuel S. , Garcia Keri E. , Gelboin-Burkhart Chelsea , Nguyen Thai B. , Rabano Ines , Stanton Rebecca , Sundararaman Balaji , Wang Ruth , Fu Xiang-Dong , Graveley Brenton R. , Yeo Gene W.
Published: April 2020

Background

A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types.

Results

Our analysis of 223 eCLIP datasets reveals a range of binding modalities, including highly resolved positioning around splicing signals and mRNA untranslated regions that associate with distinct RBP functions. Quantification of enrichment for repetitive and abundant multicopy elements reveals 70% of RBPs have enrichment for non-mRNA element classes, enables identification of novel ribosomal RNA processing factors and sites, and suggests that association with retrotransposable elements reflects multiple RBP mechanisms of action. Analysis of spliceosomal RBPs indicates that eCLIP resolves AQR association after intronic lariat formation, enabling identification of branch points with single-nucleotide resolution, and provides genome-wide validation for a branch point-based scanning model for 3′ splice site recognition. Finally, we show that eCLIP peak co-occurrences across RBPs enable the discovery of novel co-interacting RBPs.

Conclusions

This work reveals novel insights into RNA biology by integrated analysis of eCLIP profiling of 150 RBPs with distinct functions. Further, our quantification of both mRNA and other element association will enable further research to identify novel roles of RBPs in regulating RNA processing.
A simulation study comparing the power of nine tests of the treatment effect in randomized controlled trials with a time-to-event outcome
Authors: Royston Patrick , B. Parmar Mahesh K.
Published: April 2020

Background

The logrank test is routinely applied to design and analyse randomized controlled trials (RCTs) with time-to-event outcomes. Sample size and power calculations assume the treatment effect follows proportional hazards (PH). If the PH assumption is false, power is reduced and interpretation of the hazard ratio (HR) as the estimated treatment effect is compromised. Using statistical simulation, we investigated the type 1 error and power of the logrank (LR)test and eight alternatives. We aimed to identify test(s) that improve power with three types of non-proportional hazards (non-PH): early, late or near-PH treatment effects.

Methods

We investigated weighted logrank tests (early, LRE; late, LRL), the supremum logrank test (SupLR) and composite tests (joint, J; combined, C; weighted combined, WC; versatile and modified versatile weighted logrank, VWLR, VWLR2) with two or more components. Weighted logrank tests are intended to be sensitive to particular non-PH patterns. Composite tests attempt to improve power across a wider range of non-PH patterns. Using extensive simulations based on real trials, we studied test size and power under PH and under simple departures from PH comprising pointwise constant HRs with a single change point at various follow-up times. We systematically investigated the influence of high or low control-arm event rates on power.

Results

With no preconceived type of treatment effect, the preferred test is VWLR2. Expecting an early effect, tests with acceptable power are SupLR, C, VWLR2, J, LRE and WC. Expecting a late effect, acceptable tests are LRL, VWLR, VWLR2, WC and J. Under near-PH, acceptable tests are LR, LRE, VWLR, C, VWLR2 and SupLR. Type 1 error was well controlled for all tests, showing only minor deviations from the nominal 5%. The location of the HR change point relative to the cumulative proportion of control-arm events considerably affected power.

Conclusions

Assuming ignorance of the likely treatment effect, the best choice is VWLR2. Several non-standard tests performed well when the correct type of treatment effect was assumed. A low control-arm event rate reduced the power of weighted logrank tests targeting early effects. Test size was generally well controlled. Further investigation of test characteristics with different types of non-proportional hazards of the treatment effect is warranted.
Expression of interferon-regulated genes in juvenile dermatomyositis versus Mendelian autoinflammatory interferonopathies
Authors: Kim Hanna , Gunter-Rahman Fatima , McGrath John A. , Lee Esther , de Jesus Adriana A. , Targoff Ira N. , Huang Yan , O’Hanlon Terrance P. , Tsai Wanxia L. , Gadina Massimo , Miller Frederick W. , Goldbach-Mansky Raphaela , Rider Lisa G.
Published: April 2020

Background

Juvenile dermatomyositis (JDM) is a systemic autoimmune disease with a prominent interferon (IFN) signature, but the pathogenesis of JDM and the etiology of its IFN signature remain unknown. The Mendelian autoinflammatory interferonopathies, Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature (CANDLE) and STING-Associated Vasculopathy with onset in Infancy (SAVI), are caused by genetic mutations and have extremely elevated IFN signatures thought to drive pathology. The phenotypic overlap of some clinical features of CANDLE and SAVI with JDM led to the comparison of a standardized interferon-regulated gene score (IRG-S) in JDM and myositis-specific autoantibody (MSA) JDM subgroups, with CANDLE and SAVI.

Methods

A peripheral 28-component IRG-S assessed by NanoString™ in 57 JDM patients subtyped by MSA was compared with IRG-S in healthy controls (HC) and CANDLE/SAVI patients. Principal component analysis (PCA) was performed, and individual genes were evaluated for their contribution to the score. IRG-S were correlated with disease assessments and patient characteristics.

Results

IRG-S in JDM patients were significantly higher than in HC but lower than in CANDLE or SAVI. JDM IRG-S overlapped more with SAVI than CANDLE by PCA. Among MSA groups, anti-MDA5 autoantibody-positive patients’ IRG-S overlapped most with SAVI. The IFI27 proportion was significantly higher in SAVI and CANDLE than JDM, but IFIT1 contributed more to IRG-S in JDM. Overall, the contribution of individual interferon-regulated genes (IRG) in JDM was more similar to SAVI. IRG-S correlated moderately with JDM disease activity measures (rs = 0.33–0.47) and more strongly with skin activity (rs = 0.58–0.79) in anti-TIF1 autoantibody-positive patients. Weakness and joint disease activity (multinomial OR 0.91 and 3.3) were the best predictors of high IRG-S.

Conclusions

Our findings demonstrate peripheral IRG expression in JDM overlaps with monogenic interferonopathies, particularly SAVI, and correlates with disease activity. Anti-MDA5 autoantibody-positive JDM IRG-S were notably more similar to SAVI. This may reflect both a shared IFN signature, which is driven by IFN-β and STING pathways in SAVI, as well as the shared phenotype of vasculopathy in SAVI and JDM, particularly in anti-MDA5 autoantibody-positive JDM, and indicate potential therapeutic targets for JDM.
Methotrexate and relative risk of dementia amongst patients with rheumatoid arthritis: a multi-national multi-database case-control study
Authors: Newby Danielle , Prieto-Alhambra Daniel , Duarte-Salles Talita , Ansell David , Pedersen Lars , van der Lei Johan , Mosseveld Mees , Rijnbeek Peter , James Glen , Alexander Myriam , Egger Peter , Podhorna Jana , Stewart Robert , Perera Gayan , Avillach Paul , Grosdidier Solène , Lovestone Simon , Nevado-Holgado Alejo J.
Published: April 2020

Background

Inflammatory processes have been shown to play a role in dementia. To understand this role, we selected two anti-inflammatory drugs (methotrexate and sulfasalazine) to study their association with dementia risk.

Methods

A retrospective matched case-control study of patients over 50 with rheumatoid arthritis (486 dementia cases and 641 controls) who were identified from electronic health records in the UK, Spain, Denmark and the Netherlands. Conditional logistic regression models were fitted to estimate the risk of dementia.

Results

Prior methotrexate use was associated with a lower risk of dementia (OR 0.71, 95% CI 0.52–0.98). Furthermore, methotrexate use with therapy longer than 4 years had the lowest risk of dementia (odds ratio 0.37, 95% CI 0.17–0.79). Sulfasalazine use was not associated with dementia (odds ratio 0.88, 95% CI 0.57–1.37).

Conclusions

Further studies are still required to clarify the relationship between prior methotrexate use and duration as well as biological treatments with dementia risk.
Geolocation of covert communication entity on the Internet for post-steganalysis
Authors: Zhang Fan , Liu Fenlin , Luo Xiangyang
Published: April 2020

Geolocation of covert communication entity is significantly important for the forensics of the crime but has significant challenges when the steganalyst locks the guilty actor IP and wants to know the physical location of the actor. This kind of post-steganalysis involves not only the stegos transmitted on the Internet but the IP package head and content. This paper presents a geolocation method for the location of the covert communication entity based on hop-hot path coding. The method estimates the location of the covert communication entity by combining the path and delay between probes and the covert communication entity IP, which improves the deficiency that similar delays do not necessarily mean close geographical locations of the IPs. Moreover, the similarity between the IPs’ paths can be measured by coding the paths between IPs and probes. The results of a series of experiments show that the median error of the proposed method is within 6.16 km using different thresholds.
A class of new derivative-free gradient type methods for large-scale nonlinear systems of monotone equations
Authors: Fang Xiaowei
Published: April 2020

In this paper, we present a class of new derivative-free gradient type methods for large-scale nonlinear systems of monotone equations. The methods combine the RMIL conjugate gradient method, the strategy of hyperplane projection and the derivative-free line search technique. Under some appropriate assumptions, the global convergence of the given methods is established. Numerical experiments indicate that the proposed methods are effective.