bluuebunny/crossref_metadata_2025 huggingface dataset:
B Cell Compartmentalization in Blood and Cerebrospinal Fluid of HIV-Infected Ugandans with Cryptococcal Meningitis
Authors: Okurut Samuel , Meya David B. , Bwanga Freddie , Olobo Joseph , Eller Michael A. , Cham-Jallow Fatim , Bohjanen Paul R. , Pratap Harsh , Palmer Brent E. , Hullsiek Katharine H. , Manabe Yukari C. , Boulware David R. , Janoff Edward N.
Published: December 2019

Activated B cells modulate infection by differentiating into pathogen-specific antibody-producing effector plasmablasts/plasma cells, memory cells, and immune regulatory B cells. In this context, the B cell phenotypes that infiltrate the central nervous system during human immunodeficiency virus (HIV) and cryptococcal meningitis coinfection are ill defined.
Redundant and Cooperative Roles for Yersinia pestis Yop Effectors in the Inhibition of Human Neutrophil Exocytic Responses Revealed by Gain-of-Function Approach
Authors: Pulsifer Amanda R. , Vashishta Aruna , Reeves Shane A. , Wolfe Jennifer K. , Palace Samantha G. , Proulx Megan K. , Goguen Jon , Bodduluri Sobha R. , Haribabu Bodduluri , Uriarte Silvia M. , Lawrenz Matthew B.
Published: December 2019

Yersinia pestiscauses a rapid, lethal disease referred to as plague.Y. pestisactively inhibits the innate immune system to generate a noninflammatory environment during early stages of infection to promote colonization. The ability ofY. pestisto create this early noninflammatory environment is in part due to the action of seven Yop effector proteins that are directly injected into host cells via a type 3 secretion system (T3SS).
​Primary retroperitoneal pseudocyst: beware of the hoax solid enhancing adrenal mass
Authors: Farag Matthew , Gyomber Dennis , Norden Sam
Published: December 2019

​We report the case of a 55-year-old male patient with an incidental finding on CT of a ‘large adrenal mass’. The mass, which was intimately related to the left adrenal, was enhancing but not metabolically active. CT showed a 40×32 mm mass adjacent to the left adrenal and medial border of the spleen, 32 Hounsfield units (HU) precontrast and 116 HU postcontrast, consistent with a solid enhancing mass. The patient had no previous history of acute pancreatitis or any history of trauma. The patient proceeded to a laparoscopic left adrenalectomy; intraoperatively, a well-circumscribed lesion was identified intimately related to the splenic artery and able to be peeled away easily from the left adrenal. The lesion was unable to be dissected from the splenic artery and consequently the splenic artery was divided in order to completely resect this lesion. Histopathology identified the lesion as a ‘non-pancreatic fibrous pseudocyst’, with a thick calcified wall, the absence of epithelial lining and widespread inflammatory change.
Improving the quality of care with a single-entry model of referral for total joint replacement: a preimplementation/postimplementation evaluation
Authors: Damani Zaheed , Bohm Eric , Quan Hude , Noseworthy Thomas , MacKean Gail , Loucks Lynda , Marshall Deborah A
Published: December 2019

Objectives

We assessed: (1) waiting time variation among surgeons; (2) proportion of patients receiving surgery within benchmark and (3) influence of the Winnipeg Central Intake Service (WCIS) across five dimensions of quality: accessibility, acceptability, appropriateness, effectiveness, safety.

Design

Preimplementation/postimplementation cross-sectional design comparing historical (n=2282) and prospective (n=2397) cohorts.

Setting

Regional, provincial health authority.

Participants

Patients awaiting total joint replacement of the hip or knee.

Interventions

The WCIS is a single-entry model (SEM) to improve access to total hip replacement (THR) or total knee replacement (TKR) surgery, implemented to minimise variation in total waiting time (TW) across orthopaedic surgeons and increase the proportion of surgeries within 26 weeks (benchmark). Impact of SEMs on quality of care is poorly understood.

Primary and secondary outcome measures

Primary outcomes related to ‘accessibility’: waiting time variation across surgeons, waiting times (Waiting Time 2 (WT2)=decision to treat until surgery and TW=total waiting time) and surgeries within benchmark. Analysis included descriptive statistics, group comparisons and clustered regression.

Results

Variability in TW among surgeons was reduced by 3.7 (hip) and 4.3 (knee) weeks. Mean waiting was reduced for TKR (WT2/TW); TKR within benchmark increased by 5.9%. Accessibility and safety were the only quality dimensions that changed (post-WCIS THR and TKR). Shorter WT2 was associated with post-WCIS (knee), worse Oxford score (hip and knee) and having medical comorbidities (hip). Meeting benchmark was associated with post-WCIS (knee), lower Body Mass Index (BMI) (hip) and worse Oxford score (hip and knee).

Conclusions

The WCIS reduced variability across surgeon waiting times, with modest reductions in overall waits for surgery. There was improvement in some, but not all, dimensions of quality.
Complaint risk among mental health practitioners compared with physical health practitioners: a retrospective cohort study of complaints to health regulators in Australia
Authors: Veness Benjamin G , Tibble Holly , Grenyer Brin FS , Morris Jennifer M , Spittal Matthew J , Nash Louise , Studdert David M , Bismark Marie M
Published: December 2019

Objectives

To understand complaint risk among mental health practitioners compared with physical health practitioners.

Design

Retrospective cohort study, using incidence rate ratios (IRRs) to analyse complaint risk and a multivariate regression model to identify predictors of complaints.

Setting

National study using complaints data from health regulators in Australia.

Participants

All psychiatrists and psychologists (‘mental health practitioners’) and all physicians, optometrists, physiotherapists, osteopaths and chiropractors (‘physical health practitioners’) registered to practice in Australia between 2011 and 2016.

Outcome measures

Incidence rates, source and nature of complaints to regulators.

Results

In total, 7903 complaints were lodged with regulators over the 6-year period. Most complaints were lodged by patients and their families. Mental health practitioners had a complaint rate that was more than twice that of physical health practitioners (complaints per 1000 practice years: psychiatrists 119.1 vs physicians 48.0, p<0.001; psychologists 21.9 vs other allied health 7.5, p<0.001). Their risk of complaints was especially high in relation to reports, records, confidentiality, interpersonal behaviour, sexual boundary breaches and the mental health of the practitioner. Among mental health practitioners, male practitioners (psychiatrists IRR: 1.61, 95% CI 1.39 to 1.85; psychologists IRR: 1.85, 95% CI 1.65 to 2.07) and older practitioners (≥65 years compared with 36–45 years: psychiatrists IRR 2.37, 95% CI 1.95 to 2.89; psychologists IRR 1.78, 95% CI 1.47 to 2.14) were at increased risk of complaints.

Conclusions

Mental health practitioners were more likely to be the subject of complaints than physical health practitioners. Areas of increased risk are related to professional ethics, communication skills and the health of mental health practitioners themselves. Further research could usefully explore whether addressing these risk factors through training, professional development and practitioner health initiatives may reduce the risk of complaints about mental health practitioners.
Assessing the relevance and implementation of patient-centredness from the patients’ perspective in Germany: results of a Delphi study
Authors: Zeh Stefan , Christalle Eva , Hahlweg Pola , Härter Martin , Scholl Isabelle
Published: December 2019

Objective

Patient-centredness (PC) has particularly grown in relevance in health services research as well as in politics and there has been much research on its conceptualisation. However, conceptual work neglected the patients’ perspective. Thus, it remains unclear which dimensions of PC matter most to patients. This study aims to assess relevance and current degree of implementation of PC from the perspective of chronically ill patients in Germany.

Methods

We conducted a Delphi study. Patients were recruited throughout Germany using community-based strategies (eg, newspapers and support groups). In round 1, patients rated relevance and implementation of 15 dimensions of PC anonymously. In round 2, patients received results of round 1 and were asked to re-rate their own results. Participants had to have at least one of the following chronic diseases: cancer, cardiovascular disease, mental disorder or musculoskeletal disorder. Furthermore, patients had to be at least 18 years old and had to give informed consent prior to participation.

Results

226 patients participated in round 1, and 214 patients in round 2. In both rounds, all 15 dimensions were rated highly relevant, but currently insufficiently implemented. Most relevant dimensions included ‘patient safety’, ‘access to care’ and ‘patient information’. Due to small sizes of subsamples between chronic disease groups, differences could not be computed. For the other subgroups (eg, single disease vs multi-morbidity), there were no major differences.

Conclusion

This is one of the first studies assessing PC from patients’ perspective in Germany. We showed that patients consider every dimension of PC relevant, but currently not well implemented. Our results can be used to foster PC healthcare delivery and to develop patient-reported experience measures to assess PC of healthcare in Germany.
Determining the minimal important differences in the International Prostate Symptom Score and Overactive Bladder Questionnaire: results from an observational cohort study in Dutch primary care
Authors: Blanker Marco H , Alma Harma Johanna , Devji Tahira Sakina , Roelofs Marjan , Steffens Martijn G , van der Worp Henk
Published: December 2019

Objectives

To determine the minimal important difference (MID) of the International Prostate Symptom Score (IPSS) and the Overactive Bladder Questionnaire short form (OAB-q SF) assessed in primary care among patients treated for lower urinary tract symptoms (LUTS).

Design

Single-arm, open-label observational cohort study with a 6-week follow-up.

Setting

Twenty-two pharmacies in the Netherlands.

Participants

We enrolled Dutch men with uncomplicated LUTS who received a new alpha-blocker prescription from their general practitioner or urologist.

Primary and secondary outcomes

The IPSS and OAB-q SF were completed before and after 6 weeks of therapy. At 6 weeks, men also completed the Patient Global Impression of Improvement (PGI-I). The mean change scores of the IPSS and OAB-q SF were calculated for each PGI-I outcome category, with the category ‘a little better’ used to determine the MID. The SE of measurement (SEM) was calculated for each questionnaire.

Results

In total, 165 men completed follow-up. The MID was 5.2 points (95% CI 3.9 to 6.4; SEM 3.6) for the IPSS and 11.0 points (95% CI 7.1 to 14.9; SEM 9.7) for the OAB-q SF. For both questionnaires, CIs showed an overlap with the no-change categories. However, the MID for the IPSS was higher in men with severe baseline symptoms (7.1; 95% CI 5.3 to 9.0) than in men with moderate baseline symptoms (3.2; 95% CI 1.7 to 4.8).

Conclusion

In this study, the MID for the IPSS was considerably higher than the MID of 3.1 reported in the only other study on this topic, but may be due to methodological differences. Interpretation of the MID for the OAB-q SF is hampered by the overlap with the SEM. Future studies are needed to confirm our results because correlations between the PGI-I and symptom questionnaires were suboptimal.
Study protocol: an investigation of the prevalence of autism among adults admitted to acute mental health wards: a cross-sectional pilot study
Authors: Tromans Sam , Yao Guiqing Lily , Kiani Reza , Alexander Regi , Al-Uzri Mohammed , Brugha Traolach
Published: December 2019

Introduction

Autism spectrum disorders (ASDs) are associated with difficulties in social interaction, communication and restricted, repetitive behaviours. Much is known about their community prevalence among adults, data on adult inpatients within an acute mental health setting is lacking.

This pilot study aimed to estimate the prevalence of ASDs among adults admitted to acute mental health wards and to examine the association between ASDs and psychiatric and physical comorbidities within this group.

Methods and analysis

A multiple-phase approach will be used. Phase I will involve testing of 200 patients and corresponding informants, using the autism quotient (AQ), the informant version of the Social Responsiveness Scale, second edition—Adult, the self and informant versions of the Adult Social Behaviour Questionnaire and the EuroQol-5D-5L. Patients with intellectual disability (ID) will bypass Phase I.

Phase II will involve diagnostic testing of a subgroup of 40 patients with the Diagnostic Interview for Social and Communication Disorders, the Autism Diagnostic Observation Schedule version 2 and the ASD interview within the Schedules for Clinical Assessment in Neuropsychiatry version 3. 25±5 patients will not have ID and be selected via stratified random sampling according to AQ score; 15±5 patients will have ID. Phase II patients will be interviewed with the Physical Health Conditions and Mental Illness Diagnoses and Treatment sections of the 2014 Adult Psychiatric Morbidity Survey.

Prevalence estimates will be based on the proportion of Phase II participants who satisfy the 10th revision of the International Statistical Classification of Diseases and Related Health Problems Diagnostic Criteria for Research (ICD-10-DCR) and the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for ASD, adjusting for selection and non-response. Univariate analysis will be conducted for comorbidities to identify the level of their association with an ASD diagnosis.

Ethics and dissemination

Study oversight is provided by the University of Leicester. The National Health Service Health Research Authority have provided written approval. Study results will be disseminated via conference presentations and peer-reviewed publications.

Trial registration number

ISRCTN27739943
Palliative and end of life care in prisons: a mixed-methods rapid review of the literature from 2014–2018
Authors: McParland Chris , Johnston Bridget Margaret
Published: December 2019

Objectives

To explore current practice in relation to palliative and end of life care in prisons, and to make recommendations for its future provision.

Design

A rapid literature review of studies using qualitative, quantitative and mixed-methods, with a narrative synthesis of results.

Data sources

Six databases searched between January 2014 to December 2018: ASSIA, CINAHL, Embase, MEDLINE, National Criminal Justice Reference Service Abstracts and Scopus.

Eligibility criteria

Primary research articles reporting qualitative or quantitative findings about palliative and end of life care in prisons, published in peer-reviewed, English language journals between January 2014 to December 2018.

Participants

Prisoners, prisoners’ families, prison healthcare staff and other prison staff.

Data extraction/synthesis

Data extracted included: citation, design, aim, setting, sample/population, methods and key findings. Data were analysed thematically then subject to a narrative synthesis in order to answer the research questions.

Quality appraisal

Two researchers independently appraised articles using the Qualsyst tool, by Kmet et al (2004). Aggregate summary quality scores are included with findings. Articles were not excluded based on quality appraisal.

Results

23 articles were included (16 qualitative, 6 quantitative, 1 mixed methods). Top three findings (by prevalence) were: fostering relationships with people both inside and outside of prison is important to prisoners with palliative and end of life care needs, inmate hospice volunteers are able to build and maintain close relationships with the prisoners they care for and the conflicting priorities of care and custody can have a negative impact on the delivery of palliative and end of life care in prisons.

Conclusions

The key findings are: relationships are important to prisoners at the end of life, inmate hospice volunteers can build close bonds with the prisoners in their care and the prison environment and regime conflicts with best practices in palliative and end of life care. Directions for future research are also identified.

PROSPERO registration number

PROSPERO ID: CRD42019118737. Registered January 2019.
Contributing factors that influence medication errors in the prehospital paramedic environment: a mixed-method systematic review protocol
Authors: Walker Dennis , Moloney Clint , SueSee Brendan , Sharples Renee
Published: December 2019

Introduction

There is limited reliable research available on medication errors in relation to paramedic practice, with most evidence-based medication safety guidelines based on research in nursing, operating theatre and pharmacy settings. While similarities exist, evidence suggests that the prehospital environment is distinctly different in many aspects. The prevention of errors requires attention to factors from the organisational and regulatory level down to specific tasks and patient characteristics. The evidence available suggests errors may occur in up to 12.76% of medication administrations in some prehospital settings. With multiple sources stating that the errors are under-reported, this represents significant potential for patient harm. This review will seek to identify the factors influencing the occurrence of medication errors by paramedics in the prehospital environment.

Methods and analysis

The review will include qualitative and quantitative studies involving interventions or phenomena regarding medication errors or medication safety relating to paramedics (including emergency medical technicians and other prehospital care providers) within the prehospital environment. A search will be conducted using MEDLINE (Ovid), EBSCOhost Megafile Search, the International Committee of Medical Journal Editors trial registry, Google Scholar and the OpenGrey database to identify studies meeting this inclusion criteria, with initial searches commencing 30 September 2019. Studies selected will undergo assessment of methodological quality, with data to be extracted from all studies irrespective of quality. Each stage of study selection, appraisal and data extraction will be conducted by two reviewers, with a third reviewer deciding any unresolved conflicts. The review will follow a convergent integrated approach, conducting a single qualitative synthesis of qualitative and ‘qualitised’ quantitative data.

Ethics and dissemination

No ethical approval was required for this review. Findings from this systematic review will be disseminated via publications, reports and conference presentations.
Ensuring migrants’ right to health? Case of undocumented children in Israel
Authors: Moss Dana , Gutzeit Zoe , Mishori Ranit , Davidovitch Nadav , Filc Dani
Published: December 2019

After 18 years of providing government-subsidised medical insurance for children of undocumented migrants, the Israeli Ministry of Health (MOH) decided in 2018 to abruptly reverse its policy. Many children will have access to medical care only in cases of emergency. The policy change is set to potentially impact several thousands of children currently living or born in Israel. The non-profit, humanitarian sector is already seeing the impact on undocumented migrant children, with dozens of families reaching out to Physicians for Human Rights Israel to seek help accessing care for their children. These policy changes seem to be politically motivated, aiming to exclude undocumented communities from the public healthcare system as part of a general strategy of encouraging them to leave Israel. Such actions are antithetical to public health, human rights and medical ethics considerations. The Israeli Medical Association is beginning to challenge the stance of the MOH. To conform to international guidelines—both legal and medical—government ministries and relevant official bodies must follow the advice of the medical community to ensure respect for the right to health.
Content reporting of exercise interventions in rotator cuff disease trials: results from application of the Consensus on Exercise Reporting Template (CERT)
Authors: Major Daniel H , Røe Yngve , Grotle Margreth , Jessup Rebecca L , Farmer Caitlin , Småstuen Milada Cvancarova , Buchbinder Rachelle
Published: December 2019

Background

Exercise interventions are frequently recommended for patients with rotator cuff disease, but poor content reporting in clinical trials of exercise limits interpretation and replication of trials and clinicians’ ability to deliver effective exercise protocols. The Consensus on Exercise Reporting Template (CERT) was developed to address this problem.

Objective

To assess completeness of content reporting of exercise interventions in randomised controlled trials for patients with rotator cuff disease and the inter-rater reliability of the CERT.

Design

Critical appraisal.

Methods

Independent pairs of reviewers applied the CERT to all 34 exercise trials from the most recent Cochrane Review evaluating the effect of manual therapy and exercise for patients with rotator cuff disease. We used the CERT Explanation and Elaboration Statement to guide assessment of whether each of the 19-item criteria were clearly described (score 0–19; higher scores indicate better reporting). Percentage agreement and the prevalence and bias adjusted kappa (PABAK) coefficient were used to measure inter-rater reliability.

Results

The median CERT score was 5 (range 0–16). Percentage agreement was high for 15 items and acceptable for 4 items. The PABAK coefficient indicated excellent (5 items), substantial (11 items) and moderate (3 items) inter-rater agreement.

Conclusion

The description of exercise interventions for patients with rotator cuff disease in published trials is poorly reported. Overall, the inter-rater reliability of the CERT is high/acceptable. We strongly encourage journals to mandate use of the CERT for papers reporting trial protocols and results investigating exercise interventions.
Belatacept in kidney transplant patients with systemic lupus erythematosus
Authors: Carrión-Barberà Irene , Fajardo Melissa , Danias George , Tsapepas Demetra , Gartshteyn Yevgeniya , Fernandez Hilda , Askanase Anca
Published: December 2019

Objectives

Lupus nephritis (LN) requires renal replacement therapy in 10%–30% of patients. About 30% of these patients receive a kidney transplant. Belatacept is a second-generation, selective, T-cell co-stimulator blocker (inhibits cytotoxic, T-lymphocyte antigen 4, CTLA-4) used as an alternative to calcineurin inhibitors (CNI) for maintenance regimens after kidney transplantation. The pathogenic relevance of CTLA-4 inhibition and the favourable cardiovascular profile of belatacept make it an attractive therapeutic option in systemic lupus erythematosus (SLE). Intravenous administration of belatacept ensures therapeutic adherence.

Methods

This retrospective, single-centre study evaluates the outcomes of LN kidney transplant recipients treated with belatacept for reasons not related to SLE at the Columbia University Lupus and Renal Transplant Cohort.

Results

Belatacept was started in six patients on CNI regimens at 15.5±17.1 months following transplantation for LN. In five patients, creatinine levels stabilised 6 months after belatacept, one returned to haemodialysis due to CNI toxicity and pyelonephritis and one relisted for a kidney transplant following acute cellular rejection and cortical necrosis. Five patients are followed for extrarenal lupus; no extrarenal manifestations were documented in the other two patients. Data on SLE disease activity pre-belatacept and post-belatacept were available and scored in three patients using the SLE Disease Activity Index Glucocorticosteroid Index (SLEDAI-2KG), which accounts for clinical and laboratory manifestations, as well as steroid dose. Mean SLEDAI-2KG decreased from 13 to 7.6.

Conclusion

Belatacept in LN kidney transplant recipients may decrease extrarenal manifestations, attenuate CNI toxicity and stabilise allograft function, providing a better alternative to CNI regimens. Furthermore, these data suggest that belatacept, although initiated for reasons not related to SLE, might have a beneficial effect in SLE.
An optimization model for selecting wood supply contracts
Authors: Rahimi Ali , Rönnqvist Mikael , LeBel Luc , Audy Jean-François
Published: December 2019

Procurement for forest companies with pulp and paper mills aims to ensure that a sufficient volume of wood supply enters the production process. Numerous suppliers and contract types are available; however, their selection is a complex decision for procurement managers. In addition, managers typically dedicate a portion of their wood fiber demand to each group of suppliers, which is referred to as a portfolio strategy. Despite the available literature in contract selection, the consideration of contract types and their characteristics have not been addressed for the complex procurement process. In this study, a mixed-integer optimization model is proposed to best select contracts for pulp and paper procurement. The challenge was to plan deliveries in each time period to satisfy the demand of raw material at the mills. The potential of this model is demonstrated with a case study based on characteristics from a forest company in Quebec, Canada. A comparison between traditional fixed and flexible contracts is presented. Different portfolio strategies are also evaluated for groups of suppliers to investigate potential improvements.
A Novel Material Fluorescence Probe Based on Covalently Functionalized Graphene Oxide by Aminocoumarin for Detection of CN−
Authors: Ma Wenhui , Yu Zhaochuan , Li Zhongcai , Wen Jing , Zhao Baoru , Zhang Yong
Published: December 2019

Owing to the hazardness, the sensitive and selective detection of cyanide (CN−) in water or water-containing systems has still been a puzzle plaguing scientists all around the world. In this paper, a novel fluorescence probe based on covalently functionalized graphene oxide (GO) by aminocoumarin for highly selective detection of CN− in deionized water was prepared under the action of EDC/NHS. This probe bears aminocoumarin group as the recognition site and fluorophore, and its fluorescence quantum yield is increased by 0.07. Simultaneously, by loading on GO, the dispersibility, selectivity and reversibility were soundly improved, which facilitated the detection process. The fluorescence spectra showed that the probe has high selectivity and sensitivity for cyanide, and has potential application in real water.
Foundations of Query Answering on Inconsistent Databases
Authors: Wijsen Jef
Published: December 2019

Notwithstanding the traditional view that database instances must respect all integrity constraints imposed on them, it is relevant to develop theories about how to handle database instances that violate some integrity constraints, and more particularly, how to cope with query answering in the presence of inconsistency. Such a theory developed over the past twenty years is currently known as consistent query answering (CQA). The aim of this article is to summarize and discuss some core concepts and theoretical developments in CQA.
Developmental Effects of Parent–Child Separation
Authors: Waddoups Anne Bentley , Yoshikawa Hirokazu , Strouf Kendra
Published: December 2019

Parent–child separation occurs for many reasons, both involuntary and voluntary. We review the effects on children and youth of parent–child separation due to several of the most common reasons that are responsible for the growth in this family circumstance worldwide. These include early institutionalization; war, persecution, and conflict; separation during asylum; trafficking; conscription into armed conflict; and being left behind when parents migrate for economic or other reasons. Overall, the effects of parent–child separation are consistently negative on children's social-emotional development, well-being, and mental health. They are more severe when the separation is prolonged or accompanied by other forms of deprivation or victimization. Mitigating and protective factors include earlier stable family placement in the case of early institutionalization, parent–child communication and parenting quality, and community support in the host community. We conclude with an evaluation of group, school-based, and community-based interventions for children and youth affected by parent–child separation.
Comparative Approaches to Drug Pricing
Authors: Kang So-Yeon , Bai Ge , DiStefano Michael J. , Socal Mariana P. , Yehia Farah , Anderson Gerard F.
Published: December 2019

The United States relies primarily on market forces to determine prices for drugs, whereas most other industrialized countries use a variety of approaches to determine drug prices. Branded drug companies have patents and market exclusivity periods in most industrialized countries. During this period, pharmaceutical companies are allowed to set their list price as high as they prefer in the United States owing to the absence of government price control mechanisms that exist in other countries. Insured patients often pay a percentage of the list price, and cost sharing creates some pressure to lower the list price. Pharmacy benefit managers negotiate with drug companies for lower prices by offering the drug company favorable formulary placement and fewer utilization controls. However, these approaches appear to be less effective, compared with other countries’ approaches to containing branded drug prices, because prices are substantially higher in the United States. Other industrialized countries employ various forms of rate setting and price regulation, such as external reference pricing, therapeutic valuation, and health technology assessment to determine the appropriate price.
The insulin-sensitizing mechanism of myo-inositol is associated with AMPK activation and GLUT-4 expression in human endometrial cells exposed to a PCOS environment
Authors: Cabrera-Cruz Heidy , Oróstica Lorena , Plaza-Parrochia Francisca , Torres-Pinto Ignacio , Romero Carmen , Vega Margarita
Published: December 2019

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder characterized by hyperandrogenism and ovulatory dysfunction but also obesity and hyperinsulinemia. These characteristics induce an insulin-resistant state in tissues such as the endometrium, affecting its reproductive functions. Myo-inositol (MYO) is an insulin-sensitizing compound used in PCOS patients; however, its insulin-sensitizing mechanism is unclear. To understand the relationship of MYO with insulin action in endometrial cells, sodium/myo-inositol transporter 1 (SMIT-1) (MYO-transporter), and MYO effects on protein levels related to the insulin pathway were evaluated. SMIT-1 was assessed in endometrial tissue from women with normal weight, obesity, insulin resistance, and PCOS; additionally, using an in vitro model of human endometrial cells exposed to an environment resembling hyperinsulinemic-obese-PCOS, MYO effect was evaluated on p-AMPK and GLUT-4 levels and glucose uptake by Western blot, immunocytochemistry, and confocal microscopy, respectively. SMIT-1 was detected in endometrial tissue from all groups and decreased in PCOS and obesity ( P < 0.05 vs. normal weight ). In the in vitro model, PCOS conditions decreased p-AMPK levels, while they were restored with MYO ( P < 0.05). The diminished GLUT-4 protein levels promoted by PCOS environment were restored by MYO through SMIT-1 and p-AMPK-dependent mechanism ( P < 0.05). Also, MYO restored glucose uptake in cells under PCOS condition through a p-AMPK-dependent mechanism. Finally, these results were similar to those obtained with metformin treatment in the same in vitro conditions. Consequently, MYO could be a potential insulin sensitizer through its positive effects on insulin-resistant tissues as PCOS-endometrium, acting through SMIT-1, provoking AMPK activation and elevated GLUT-4 levels and, consequently, increase glucose uptake by human endometrial cells. Therefore, MYO may be used as an effective treatment option in insulin-resistant PCOS women.
Effect of Single Injection of Recombinant Human Bone Morphogenetic Protein-2-Loaded Artificial Collagen-Like Peptide in a Mouse Segmental Bone Transport Model
Authors: Tazawa Ryo , Minehara Hiroaki , Matsuura Terumasa , Kawamura Tadashi , Uchida Kentaro , Inoue Gen , Saito Wataru , Takaso Masashi
Published: December 2019

This study aimed to investigate whether a single injection of recombinant human bone morphogenetic protein-2-loaded artificial collagen-like peptide gel (rhBMP-2/ACG) accelerates consolidation at the bone defect site and bone union at the docking site in a mouse segmental bone transport (SBT) model. A critical sized bone defect (2 mm) was created in the femur of mice and subsequently reconstructed using SBT with an external fixator. Mice were divided into four treatment groups: Group CONT (immobile control), Group 0.2 (bone segments moved 0.2 mm/day for 10 days), Group 1.0 (bone segments moved 1.0 mm/day for 2 days), and Group 1.0/BMP-2 (rhBMP-2/ACG injected into the bone defect and segments moved 1.0 mm/day for 2 days). Consolidation at the bone defect site and bone union at the docking site was evaluated radiologically and histologically across eight weeks. Bone volume and bone mineral content were significantly higher in Group 0.2 than in Group 1.0. Group 0.2 showed evidence of rebuilding of the medullary canal eight weeks after surgery at the bone defect site. However, in Group 1.0, maturation of regenerative bone at the bone defect site was poor, with the central area between the proximal and distal bone composed mainly of masses of fibrous and adipose tissue. Group 1.0/BMP-2 had higher bone volume and bone mineral content compared to Group 1.0, and all mice achieved bone union at the bone defect and docking sites. Single injection of rhBMP-2/ACG combined with SBT may be effective for enhancing bone healing in large bone defects.
Design and Quantitative Analysis of Cancer Detection System Based on Fluorescence Immune Analysis
Authors: Shao Lei , Zhang Longyu , Li Shilin , Zhang Pengyuan
Published: December 2019

Human blood is an important medical detection index. With the development in clinical medical detection instruments and detection technology, the requirements for detection accuracy and efficiency have been gradually improved. Fluorescent immunochromatography is a new detection technique. It has the characteristics of high efficiency, convenience, no pollution, and wide detection range. Human blood can be detected quickly using fluorescent immunochromatography. At present, it has received great attention from the field of clinical testing. In this paper, a set of fluorescent immunochromatographic analyzer has been designed. It is mainly based on the principle of fluorescence immunochromatography. A new method of signal analysis and system design for fluorescent immunochromatography analyzer is proposed. By using the improved threshold function denoising algorithm, the quantitative detection of fluorescent immunochromatographic strip is realized. The concentration of pathogenic factors (cancer cells) in human serum can be measured conveniently and accurately. The system integrates many peripheral modules, including fluorescence signal acquisition, fluorescence signal processing, quantitative curve fitting, and test results. In this paper, the quantitative detection experiments of the system are carried out in three aspects: linearity, repeatability, and sensitivity. The experimental results show that the linear correlation coefficient is up to 0.9976, and the limit of detection is up to 0.05 ng/ml. The requirements of the system are satisfied. The system performance is good, and the quantitative result is accurate. Therefore, the establishment of a fluorescence analysis system is of great significance.
A Nonlinear Method for Component Separation of Dam Effect Quantities Using Kernel Partial Least Squares and Pseudosamples
Authors: Yin Wenzhong , Zhao Erfeng , Gu Chongshi , Huang Hao , Yang Yang
Published: December 2019

Existing component separation methods fail to consider the complex nonlinear relationship between dam effect quantities and environmental variables. In this study, a novel nonlinear component separation method for the effect quantities is proposed by combining kernel partial least squares (KPLS) and pseudosamples. By this method, a nonlinear monitoring model is established based on KPLS, and the complicated nonlinear relationship between the effect quantities and environmental variables can be determined accurately through the model. Furthermore, special pseudosamples are constructed to separate independent components and coupling influence components of environmental factors from the KPLS model. These methods have been applied into a super‐high arch dam, and the separated displacement components conform to the general deformation law. The presented results indicate that it is more reliable than traditional multiple linear regression models.
Age- and Sex-Specific Reference Intervals for Myocardial Enzyme Activity in Healthy Chinese Han Population Aged 1∼<18 years
Authors: Guo Wenjia , Zhou Qi , Jia Yanan , Xu Jiancheng
Published: December 2019

Age- and sex-specific reference intervals (RIs) for myocardial enzyme activity of children and adolescents are not available in China. Our study aimed to establish age- and gender-related RIs for AST, LDH, CK, and CKMB activity in healthy Chinese Han population aged 1∼<18 years. Healthy Han children and adolescents (n = 6322, 1∼<18 years old) were assessed from completed questionnaires and defined criteria from communities and schools in 5 administrative districts of Jilin Province from September 2017 to December 2018. Measurements of AST, LDH, CK, and CKMB activity were performed on the VITROS 5600 Integrated System. Percentiles of enzyme activity were completed by LMS. RIs were established by Medcalc according to the EP28-A3c guidelines issued by the Clinical and Laboratory Standards Institute. AST declined rapidly during 1∼<6 years and had been subsided during 11∼<18 years, though LDH decreased at a steady rate. CK activity stabilized while CKMB showed a downward trend. Sex differences started after age 12 when males presented higher results. There were significant differences comparing with domestic and other countries’ experiments which applied similar methodologies. Enzymes were associated with age and sex, while age had greater impact. We established age- and sex-specific RIs of serum AST, LDH, CK, and CKMB activities for Chinese children and adolescents using the VITROS 5600 Integrated System for the first time. These data will lay the groundwork for the next horizon in pediatric RIs as well as improve test result interpretation for pediatric illness.
Statistical Modeling of HIV, Tuberculosis, and Hepatitis B Transmission in Ghana
Authors: Twumasi Clement , Asiedu Louis , Nortey Ezekiel N. N.
Published: December 2019

Most mortality studies usually attribute death to single disease, while various other diseases could also act in the same individual or a population at large. Few works have been done by considering HIV, Tuberculosis (TB), and Hepatitis B (HB) as jointly acting in a population in spite of their high rate of infections in Ghana. This study applied competing risk methods on these three diseases by assuming they were the major risks in the study population. Among all opportunistic infections that could also act within HIV-infected individuals, TB has been asserted to be the most predominant. Other studies have also shown cases of HIV and Hepatitis B coinfections. The validity of these comorbidity assertions was statistically determined by exploring the conditional dependencies existing among HIV, TB, and HB through Bayesian networks or directed graphical model. Through Classification tree, sex and age group of individuals were found as significant demographic predictors that influence the prevalence of HIV and TB. Females were more likely to contract HIV, whereas males were prone to contracting TB.
Numbness and Weakness Recovered at a Less Extent in Patients with Lumbar Disc Herniation after Percutaneous Endoscopic Lumbar Discectomy
Authors: Wang Yuming , Gao Fuqiang , Zou Haibo
Published: December 2019

Background. Patients with lumbar disc herniation (LDH) may present with motor disorders and various sensory disorders, among which pain and numbness are the most common ones. Percutaneous endoscopic lumbar discectomy (PELD) is reported to be both safe and effective. However, most of the previous studies focused on the recovery of pain, and the relief extent of numbness and weakness has rarely been reported. The Sciatica Bothersomeness Index (SBI) is a self-assessment tool for LDH patients. It has demonstrated acceptable reliability, construct validity, and responsiveness. Objectives. Our aim was to explore the curative effect of percutaneous endoscopic lumbar discectomy and to compare the various extent of relief among pain, numbness, and weakness. Methods. The medical records of patients admitted for LDH from September 2016 to December 2018 were collected, and the patients were followed up for 3 months to evaluate the relief of their clinical symptoms. Preoperative and postoperative total scores and subitem scores of SBI were compared to evaluate the relief of pain, numbness, and weakness. Surgical outcomes of PELD were evaluated by the Nakai score, and patients were divided into two groups accordingly, which were the relief group (excellent and good in the Nakai score) and the less relief group (fair and poor in the Nakai score). Risk factors for PELD outcomes and preoperative presence of numbness and/or weakness were analyzed by the logistic model, and p value less than 0.05 was considered significant. Results. A total of 86 patients met the inclusion criteria and acquired 3 months follow-up. Relief extent of pain, numbness, and weakness, was 82%, 41%, and 21%, respectively. There were 71 cases in the relief group and 15 cases in the less relief group. Results of the logistic regression analysis showed that the preoperative pain score of SBI (p=0.002; OR: 1.647 (1.199–2.261)) was a relatively independent risk factor for PELD outcomes, and multiplicativity of duration of preoperative symptoms and imaging grade [p=0.004; OR: 1.015 (1.005–1.026)] was a relatively independent risk factor for preoperative presence of numbness and/or weakness. Conclusions. PELD had a good curative effect in the treatment of LDH. Patients of LDH recovered best from pain, followed by numbness and weakness after PELD. Higher level of patients self-reported preoperative pain indicated a better surgical outcome for LDH patients, and preoperative long duration of symptoms together with a severe compression of nerve root significantly increased the risk of presenting numbness and/or weakness.
Assessment of the Relaxation-Enhancing Properties of a Nitroxide-Based Contrast Agent TEEPO-Glc with In Vivo Magnetic Resonance Imaging
Authors: Soikkeli Maiju , Kettunen Mikko I. , Nivajärvi Riikka , Olsson Venla , Rönkkö Seppo , Laakkonen Johanna P. , Lehto Vesa-Pekka , Kavakka Jari , Heikkinen Sami
Published: December 2019

Magnetic resonance imaging examinations are frequently carried out using contrast agents to improve the image quality. Practically all clinically used contrast agents are based on paramagnetic metals and lack in selectivity and specificity. A group of stable organic radicals, nitroxides, has raised interest as new metal-free contrast agents for MRI. Their structures can easily be modified to incorporate different functionalities. In the present study, a stable nitroxide TEEPO (2,2,6,6-tetraethylpiperidin-1-oxyl) was linked to a glucose moiety (Glc) to construct a water-soluble, potentially tumor-targeting compound with contrast-enhancing ability. The ability was assessed with in vivo MRI experiments. The constructed TEEPO-Glc agent proved to shorten the T1 relaxation time in tumor, while the T1 time in healthy brain tissue remained the same. The results indicate the potential of TEEPO-Glc as a valuable addition to the growing field of metal-free contrast enhancement in MRI-based diagnostics.
A Computational and Structural Database Study of the Metal-Carbene Bond in Groups IA, IIA, and IIIA Imidazol-2-Ylidene Complexes
Authors: Tetteh Samuel
Published: December 2019

Imidazol-2-ylidenes are important N-heterocyclic carbenes which have become universal ligands in organometallic and coordination chemistry. Generally classified as σ-donor ligands, these compounds have been used to stabilize various metal complexes which hitherto were less stable in their catalytic processes. Herein, the number and distribution of group IA, group IIA, and group IIIA metal-imidazol-2-ylidene complexes retrieved from the Cambridge Structural Database (CSD) are assessed. The data showed that the mean M-Ccarbene bond length increases with increasing ionic size but is similar across each diagonal. Dominant factors such as Lewis acidity and electrostatic attractions were found to control the bonding modes of the respective ions. Generally, the metal ions show preference for tetrahedral coordination with larger cations forming complexes with higher coordination numbers. For their high number of entries (101), tetrahedrally coordinated boron complexes with various electron withdrawing and electron donating groups were studied computationally at the DFT/B3LYP level of theory. The strength of the B-Ccarbene bond was found to depend on steric interactions between bulky groups on the borenium atom and substituents on the N-positions of the imidazol-2-ylidene ligand. This observation was further confirmed by estimation of the binding energy, natural charge, and the electron distribution in the B-Ccarbene bond.
Rainfall and Atmospheric Temperature against the Other Climatic Factors: A Case Study from Colombo, Sri Lanka
Authors: Perera Anushka , Rathnayake Upaka
Published: December 2019

Climate prediction is given a high priority by many countries due to its importance in mitigation of extreme weather conditions. However, the prediction is not an easy task as the climatic parameters not only show spatial variations but also temporal variations. In addition, the climatic parameters are interrelated. To overcome these difficulties, soft computing techniques are widely used in prediction of climate variables with respect to the other variables. On the other hand, Colombo, Sri Lanka, is experiencing adverse or extreme weather conditions over the last few years. However, a climate prediction study is yet to be carried out in this tropical climatic zone. Therefore, this paper presents a study, identifying relationships between the two most impacted climate parameters (atmospheric temperature and rainfall) and other climatic parameters. Artificial neural network (ANN) models are developed to define the relationships and then to predict the atmospheric temperature as a function of other parameters including monthly rainfall, minimum and maximum relative humidity, and average wind speed. Same analysis is carried out to define the prediction model to the monthly rainfall. The best algorithm out of several other ANN algorithms is chosen for the analyses. Results revealed that the atmospheric temperature in Colombo can be presented with respect to the other climatic variables. However, the rainfall does not show a greater relationship with the other climatic parameters.