bluuebunny/crossref_metadata_2025 huggingface dataset:
PUMAS: fine-tuning polygenic risk scores with GWAS summary statistics
Authors: Zhao Zijie , Yi Yanyao , Song Jie , Wu Yuchang , Zhong Xiaoyuan , Lin Yupei , Hohman Timothy J. , Fletcher Jason , Lu Qiongshi
Published: September 2021

Polygenic risk scores (PRSs) have wide applications in human genetics research, but often include tuning parameters which are difficult to optimize in practice due to limited access to individual-level data. Here, we introduce PUMAS, a novel method to fine-tune PRS models using summary statistics from genome-wide association studies (GWASs). Through extensive simulations, external validations, and analysis of 65 traits, we demonstrate that PUMAS can perform various model-tuning procedures using GWAS summary statistics and effectively benchmark and optimize PRS models under diverse genetic architecture. Furthermore, we show that fine-tuned PRSs will significantly improve statistical power in downstream association analysis.
Patient perceptions of the challenges of recruitment to a renal randomised trial registry: a pilot questionnaire-based study
Authors: Murphy Ellen , O’Keeffe Aoife , O Shea Niamh , Long Eva , Eustace Joseph A. , Shiely Frances
Published: September 2021

Background

Randomised controlled trials (RCTs) are the gold standard for demonstrating the efficacy of new therapies. However, issues of external validity often affect result application to real-world settings. Using registries to conduct RCTs is a reasonably new practice, but is appealing because it combines the benefits of both observational studies and RCTs. There is limited literature on patient motivators, barriers, and consent to registries for conducting RCTs. The purpose of our study was to establish the factors that motivate and/or inhibit patients from joining a registry for RCTs and to determine what information matters to patients when making an enrolment decision to participate in such a registry.

Methods

We conducted a cross-sectional questionnaire-based study at a dialysis centre in Southwest Ireland representing a catchment patient population of approximately 430,000. Quantitative data were coded and analysed in SPSS (v16). Descriptive statistics were produced, and open-ended questions were analysed by thematic analysis.

Results

Eighty-seven patients completed the questionnaire. Reasons for participation in a registry included personal and altruistic benefits. Barriers to participation were time and travel requirements associated with registry participation, data safety concerns, risks, side effects, and concerns that registry participation would impact current treatment. Although 29.8% of patients expressed concern regarding their data being stored in a registry, 79.3% were still willing to consent to have their data uploaded and stored in a registry for conducting RCTs. It was important to patients to have their GP (general practitioner) involved in the decision to participate, despite little day-to-day contact with their GP for renal dialysis management.

Conclusion

Challenges to recruitment to registries for RCTs exist, but addressing the identified concerns of potential participants may aid patients in making a more informed enrolment decision and may improve recruitment to registries, and by extension, to RCTs conducted using the registry.
Power and sample size calculation for stepped-wedge designs with discrete outcomes
Authors: Xia Fan , Hughes James P. , Voldal Emily C. , Heagerty Patrick J.
Published: September 2021

Background

Stepped-wedge designs (SWD) are increasingly used to evaluate the impact of changes to the process of care within health care systems. However, to generate definitive evidence, a correct sample size calculation is crucial to ensure such studies are properly powered. The seminal work of Hussey and Hughes (Contemp Clin Trials 28(2):182–91, 2004) provides an analytical formula for power calculations with normal outcomes using a linear model and simple random effects. However, minimal development and evaluation have been done for power calculation with non-normal outcomes on their natural scale (e.g., logit, log). For example, binary endpoints are common, and logistic regression is the natural multilevel model for such clustered data.

Methods

We propose a power calculation formula for SWD with either normal or non-normal outcomes in the context of generalized linear mixed models by adopting the Laplace approximation detailed in Breslow and Clayton (J Am Stat Assoc 88(421):9–25, 1993) to obtain the covariance matrix of the estimated parameters.

Results

We compare the performance of our proposed method with simulation-based sample size calculation and demonstrate its use on a study of patient-delivered partner therapy for STI treatment and a study that assesses the impact of providing additional benchmark prevalence information in a radiologic imaging report. To facilitate adoption of our methods we also provide a function embedded in the R package “swCRTdesign” for sample size and power calculation for multilevel stepped-wedge designs.

Conclusions

Our method requires minimal computational power. Therefore, the proposed procedure facilitates rapid dynamic updates of sample size calculations and can be used to explore a wide range of design options or assumptions.
Protocol for a multi-phase, mixed methods study to develop and evaluate culturally adapted CBT to improve community mental health services for Canadians of south Asian origin
Authors: Naeem Farooq , Tuck Andrew , Mutta Baldev , Dhillon Puneet , Thandi Gary , Kassam Azaad , Farah Nimo , Ashraf Aamna , Husain M. Ishrat , Husain M. Omair , Vasiliadis Helen-Maria , Sanches Marcos , Munshi Tariq , Abbott Maureen , Watters Nicholas , Kidd Sean A. , Ayub Muhammad , McKenzie Kwame
Published: September 2021

Background

Canadians of South Asian (SA) origin comprise the largest racialized group in Canada, representing 25.6% of what Statistics Canada terms “visible minority populations”. South Asian Canadians are disproportionately impacted by the social determinants of health, and this can result in high rates of mood and anxiety disorders. These factors can negatively impact mental health and decrease access to care, thereby increasing mental health inequities. Cognitive Behavioural Therapy (CBT) in its current form is not suitable for persons from the non-western cultural backgrounds. Culturally adapted Cognitive Behavioural Therapy (CaCBT) is an evidence-based practice. CaCBT is more effective than standard CBT and can reduce dropouts from therapy compared with standard CBT. Thus, CaCBT can increase access to mental health services and improve outcomes for immigrant, refugee and ethno-cultural and racialized populations. Adapting CBT for growing SA populations in Canada will ensure equitable access to effective and culturally appropriate interventions.

Methods

The primary aim of the study is to develop and evaluate CaCBT for Canadian South Asian persons with depression and anxiety and to gather data from stakeholders to develop guidelines to culturally adapt CBT. This mixed methods study will use three phases: (1) cultural adaptation of CBT, (2) pilot feasibility of CaCBT and (3) implementation and evaluation of CaCBT. Phase 1 will use purposive sampling to recruit individuals from four different groups: (1) SA patients with depression and anxiety, (b) caregivers and family members of individuals affected by anxiety and depression, (c) mental health professionals and (d) SA community opinion leaders. Semi-structured interviews will be conducted virtually and analysis of interviews will be informed by an ethnographic approach. Phase 2 will pilot test the newly developed CaCBT for feasibility, acceptability and effectiveness via quantitative methodology and a randomized controlled trial, including an economic analysis. Phase 3 will recruit therapists to train and evaluate them in the new CaCBT.

Discussion

The outcome of this trial will benefit health services in Canada, in terms of helping to reduce the burden of depression and anxiety and provide better care for South Asians. We expect the results to help guide the development of better services and tailor existing services to the needs of other vulnerable groups.

Trial registration

ClinicalTrials.govNCT04010890. Registered on July 8, 2019
The praziquantel in preschoolers (PIP) trial: study protocol for a phase II PK/PD-driven randomised controlled trial of praziquantel in children under 4 years of age
Authors: Webb Emily L. , Edielu Andrew , Wu Hannah W. , Kabatereine Narcis B. , Tukahebwa Edridah M. , Mubangizi Alfred , Adriko Moses , Elliott Alison M. , Hope William W. , Mawa Patrice A. , Friedman Jennifer F. , Bustinduy Amaya L.
Published: September 2021

Background

Over 200 million individuals worldwide are infected with Schistosoma species, with over half of infections occurring in children. Many children experience first infections early in life and this impacts their growth and development; however praziquantel (PZQ), the drug used worldwide for the treatment of schistosomiasis, only has regulatory approval among adults and children over the age of four, although it is frequently used “off label” in endemic settings. Furthermore, pharmacokinetic/pharmacodynamics (PK/PD) evidence suggests the standard PZQ dose of 40 mg/kg is insufficient in preschool-aged children (PSAC). Our goal is to understand the best approaches to optimising the treatment of PSAC with intestinal schistosomiasis.

Methods

We will conduct a randomised, controlled phase II trial in a Schistosoma mansoni endemic region of Uganda and a Schistosoma japonicum endemic region of the Philippines. Six hundred children, 300 in each setting, aged 12–47 months with Schistosoma infection will be randomised in a 1:1:1:1 ratio to receive either (1) 40 mg/kg PZQ at baseline and placebo at 6 months, (2) 40 mg/kg PZQ at baseline and 40 mg/kg PZQ at 6 months, (3) 80 mg/kg PZQ at baseline and placebo at 6 months, or (4) 80 mg/kg PZQ at baseline and 80 mg/kg PZQ at 6 months. Following baseline treatment, children will be followed up for 12 months. The co-primary outcomes will be cure rate and egg reduction rate at 4 weeks. Secondary outcomes include drug efficacy assessed by novel antigenic endpoints at 4 weeks, actively collected adverse events and toxicity for 12 h post-treatment, morbidity and nutritional outcomes at 6 and 12 months, biomarkers of inflammation and environmental enteropathy and PZQ PK/PD parameters.

Discussion

The trial will provide valuable information on the safety and efficacy of the 80 mg/kg PZQ dose in PSAC, and on the impact of six-monthly versus annual treatment, in this vulnerable age group.

Trial registration

ClinicalTrials.gov NCT03640377. Registered on 21 Aug 2018.
A comprehensive study of the promoting effect of manganese on white rot fungal treatment for enzymatic hydrolysis of woody and grass lignocellulose
Authors: Fu Xiao , Zhang Jialong , Gu Xiangyu , Yu Hongbo , Chen Shulin
Published: September 2021

Background

The efficiency of biological systems as an option for pretreating lignocellulosic biomass has to be improved to make the process practical. Fungal treatment with manganese (Mn) addition for improving lignocellulosic biomass fractionation and enzyme accessibility were investigated in this study. The broad-spectrum effect was tested on two different types of feedstocks with three fungal species. Since the physicochemical and structural properties of biomass were the main changes caused by fungal degradation, detailed characterization of biomass structural features was conducted to understand the mechanism of Mn-enhanced biomass saccharification.

Results

The glucose yields of fungal-treated poplar and wheat straw increased by 2.97- and 5.71-fold, respectively, after Mn addition. Particularly, over 90% of glucose yield was achieved in Mn-assisted Pleurotus ostreatus-treated wheat straw. A comparison study using pyrolysis gas chromatography mass spectrometry (Py-GC/MS) and two-dimensional 1H–13C heteronuclear single quantum coherence (2D HSQC) nuclear magnetic resonance (NMR) spectroscopy was conducted to elucidate the role of Mn addition on fungal disruption of the cross-linked structure of whole plant cell wall. The increased Cα-oxidized products was consistent with the enhanced cleavage of the major β-O-4 ether linkages in poplar and wheat straw lignin or in the wheat straw lignin–carbohydrate complexes (LCCs), which led to the reduced condensation degree in lignin and decreased lignin content in Mn-assisted fungal-treated biomass. The correlation analysis and principal component analysis (PCA) further demonstrated that Mn addition to fungal treatment enhanced bond cleavage in lignin, especially the β-O-4 ether linkage cleavage played the dominant role in removing the biomass recalcitrance and contributing to the glucose yield enhancement. Meanwhile, enhanced deconstruction of LCCs was important in reducing wheat straw recalcitrance. The findings provided not only mechanistic insights into the Mn-enhanced biomass digestibility by fungus, but also a strategy for improving biological pretreatment efficiency of lignocellulose.

Conclusion

The mechanism of enhanced saccharification of biomass by Mn-assisted fungal treatment mainly through Cα-oxidative cleavage of β-O-4 ether linkages further led to the decreased condensation degree in lignin, as a result, biomass recalcitrance was significantly reduced by Mn addition.

Graphic abstract
Sand fly fauna of South-Eastern Romania, with the description of Phlebotomus (Transphlebotomus) simonahalepae n. sp. (Diptera: Psychodidae)
Authors: Cazan Cristina Daniela , Sándor Attila D. , Erisoz Kasap Ozge , Alten Bulent , Mihalca Andrei Daniel
Published: September 2021

Background

An entomological study was conducted in the Canaraua Fetii Special Protection Area in the Dobrogea region, South-Eastern Romania. Four sand fly species were recorded at this location between 1968 and 1970: Phlebotomus neglectus, Ph. balcanicus, Ph. sergenti and Sergentomyia minuta. The most abundant sand fly species recorded at that time were Ph. balcanicus and Se. minuta. In the context of a countrywide study to update the sand fly species diversity, we surveyed the same area, recording also a previously unknown Ph. (Transphlebotomus) sp., for which we provide a formal description here.

Methods

Sand flies were collected between July and August in 2018 and 2019 in three sites from Canaraua Fetii, Dobrogea region, Romania. The general aspect of the landscape is of a canyon (vertical, narrow walls and deep valleys). Species identification was done using both morphological and molecular analyses.

Results

Out of 645 collected sand flies, 644 (99.8%) were morphologically identified as Ph. neglectus, while one female specimen (0.2%) was assigned to a previously unknown species, belonging to the subgenus Transphlebotomus. The morphological and molecular examination of this specimen showed that it is a previously unknown species which we formally describe here as Phlebotomus (Transphlebotomus) simonahalepae n. sp. Also, Ph. balcanicus, Ph. sergenti, and Se. minuta (previously recorded in this location) were not present.

Conclusions

The study revealed for the first time the presence of sand flies of the subgenus Transphlebotomus in Romania. Moreover, a new species, Ph. simonahalepae n. sp., was described based on a female specimen, raising the number of species in this subgenus to six. In the investigated natural habitat, the predominant species was Ph. neglectus instead of Ph. balcanicus and Se. minuta (recorded as the predominant species in 1968–1970).

Graphical abstract
Molecular phylogeny of the Anopheles hyrcanus group (Diptera: Culicidae) based on rDNA–ITS2 and mtDNA–COII
Authors: Zhang Canglin , Yang Rui , Wu Linbo , Luo Chunhai , Guo Xiaofang , Deng Yan , Zhou Hongning , Zhang Yilong
Published: September 2021

Background

The Anopheles hyrcanus group, which includes 25 species, is widely distributed in the Oriental and Palaearctic regions. Given the difficulty in identifying cryptic or sibling species based on their morphological characteristics, molecular identification is regarded as an important complementary approach to traditional morphological taxonomy. The aim of this study was to reconstruct the phylogeny of the Hyrcanus group using DNA barcoding markers in order to determine the phylogenetic correlations of closely related taxa and to compare these markers in terms of identification efficiency and genetic divergence among species.

Methods

Based on data extracted from the GenBank database and data from the present study, we used 399 rDNA–ITS2 sequences of 19 species and 392 mtDNA–COII sequences of 14 species to reconstruct the molecular phylogeny of the Hyrcanus group across its worldwide range. We also compared the performance of rDNA–ITS2 against that of mtDNA–COII to assess the genetic divergence of closely related species within the Hyrcanus group.

Results

Average interspecific divergence for the rDNA–ITS2 sequence (0.376) was 125-fold higher than the average intraspecies divergence (0.003), and average interspecific divergence for the mtDNA–COII sequence (0.055) was eightfold higher than the average intraspecies divergence (0.007). The barcoding gap ranged from 0.015 to 0.073 for rDNA–ITS2, and from 0.017 to 0.025 for mtDNA–COII. Two sets of closely related species, namely, Anophels lesteri and An. paraliae, and An. sinensis, An. belenrae and An. kleini, were resolved by rDNA–ITS2. In contrast, the relationship of An. sinensis/An. belenrae/An. kleini was poorly defined in the COII tree. The neutrality test and mismatch distribution revealed that An. peditaeniatus, An. hyrcanus, An. sinensis and An. lesteri were likely to undergo hitchhiking or population expansion in accordance with both markers. In addition, the population of an important vivax malaria vector, An. sinensis, has experienced an expansion after a bottleneck in northern and southern Laos.

Conclusions

The topology of the Hyrcanus group rDNA–ITS2 and mtDNA–COII trees conformed to the morphology-based taxonomy for species classification rather than for that for subgroup division. rDNA–ITS2 is considered to be a more reliable diagnostic tool than mtDNA–COII in terms of investigating the phylogenetic correlation between closely related mosquito species in the Hyrcanus group. Moreover, the population expansion of an important vivax malaria vector, An. sinensis, has underlined a potential risk of malaria transmission in northern and southern Laos. This study contributes to the molecular identification of the Anopheles hyrcanus group in vector surveillance.

Graphical abstract
Insecticidal efficacy of fluralaner (Bravecto®) against Triatoma brasiliensis, a major vector of Trypanosoma cruzi in Brazil
Authors: Queiroga Tamyres Bernadete Dantas , Gomez Luanderson Cardoso Pereira , de Sena Eduardo Rodrigues , dos Santos Wilo Victor , Ferreira Henrique Rafael Pontes , de Araújo-Neto Vicente Toscano , Barbosa-Silva Andressa Noronha , Brito Carlos Ramon do Nascimento , Lima Romeika Karla dos Reis , Fagundes-Neto João Ciro , Galvão Lúcia Maria da Cunha , de Medeiros Henrique Rocha , da Câmara Antônia Cláudia Jácome , Nascimento Manuela Sales Lima , Gama Renata Antonaci , Guedes Paulo Marcos Matta
Published: September 2021

Background

Triatomines are responsible for the vector transmission of the protozoan parasite Trypanosoma cruzi, which causes Chagas disease. Triatoma brasiliensis is the main vector of the parasite in Brazil, and dogs are an important reservoir of the parasite. The aim of this study was to evaluate the insecticidal effect of fluralaner (Bravecto®) on T. brasiliensis after a blood meal in treated dogs.

Methods

Healthy mongrel dogs (n = 8) were recruited from the Zoonoses Control Center (ZCC) in the city of Natal, Rio Grande do Norte, Brazil, and randomized into two groups, a fluralaner (Bravecto®)-treated group (n = 4) and a control group (n = 4). Colony-reared third-, fourth- and fifth-instar nymphs of T. brasiliensis nymphs (n = 10) were allowed to feed on dogs from both groups for 30–40 min, once monthly, for up to 12 months. Bug mortality was observed up to 5 days after each blood meal.

Results

Mortality in triatomines which had a blood meal on fluralaner (Bravecto®)-treated dogs was 100% for up to 7 months after treatment, with mortality decreasing to 66.4% after 8 months, 57% after 9 months, 35% after 10 months, 10% after 11 months and 0% after 12 months. The mortality of triatomines that fed on non-treated control dogs was always ≤ 2.5%.

Conclusions

Our results suggest that fluralaner (Bravecto®) treatment of dogs induces long-term mortality of T. brasiliensis after the blood meal. This is a potential approach to be used to control vector transmission of T. cruzi, the etiological agent of Chagas disease, especially in endemic areas.

Graphical Abstract
Role of serial cardiac 18F-FDG PET-MRI in Anderson–Fabry disease: a pilot study
Authors: Nappi Carmela , Ponsiglione Andrea , Pisani Antonio , Riccio Eleonora , Di Risi Teodolinda , Pieroni Maurizio , Klain Michele , Assante Roberta , Acampa Wanda , Nicolai Emanuele , Spinelli Letizia , Cuocolo Alberto , Imbriaco Massimo
Published: September 2021

Aim

We investigated the value of serial cardiac18F-FDG PET-MRI in Anderson–Fabry disease (AFD) and the potential relationship of imaging results with FASTEX score.

Methods and results

Thirteen AFD patients underwent cardiac18F-FDG PET-MRI at baseline and follow-up. Coefficient of variation (COV) of FDG uptake and FASTEX score were assessed. At baseline, 9 patients were enzyme replacement therapy (ERT) naïve and 4 patients were under treatment. Two patients presented a FASTEX score of 0 indicating stable disease and did not show any imaging abnormality at baseline and follow-up PET-MRI. Eleven patients had a FASTEX score > 20% indicating disease worsening. Four of these patients without late gadolinium enhancement (LGE) and with normal COV at baseline and follow-up had a FASTEX score of 35%. Three patients without LGE and with abnormal COV at baseline and follow-up had a FASTEX score ranging from 30 to 70%. Three patients with LGE and abnormal COV at baseline and follow-up had a FASTEX score between 35 and 75%. Finally, one patient with LGE and normal COV had a FASTEX score of 100%. Of the 12 patients on ERT at follow-up, FASTEX score was significantly higher in those 4 showing irreversible cardiac injury at baseline compared to 8 with negative LGE (66 ± 24 vs. 32 ± 21,p = 0.03).

Conclusion

18F-FDG PET-MRI may be effective to monitor cardiac involvement in AFD.
Long-acting reversible contraception utilization and associated factors among women in extended postpartum period in southern Ethiopia
Authors: Mesfin Yibeltal , Wallelign Abraham
Published: September 2021

Background

Postpartum long-acting reversible contraceptive is important to prevent unintended and closed spaced pregnancy following the first 12 months of childbirth. Few data were available on postpartum long-acting reversible contraceptive use in Ethiopia. So, this study aimed to assess the long-acting reversible contraception use and associated factors among women who gave birth in the last 12 months.

Methods

A community-based cross-sectional study was conducted from October 1st to November 2019. Systematic random sampling was applied to recruit a total of 416 study participants. Data were collected using a structured questionnaire. Data were entered using Epidata 4.6 and exported to SPSS version 25 for analysis. P-value < 0.05 with 95% confidence interval (CI) used to declare statistical significance.

Result

In this study, long acting contraceptive utilization among women in the extended postpartum period was 22.6%. Maternal age ≤ 24 years (AOR = 3.7, 95% CI: 1.5, 8.9), being married (AOR =3.5 95% CI: (1.17–10.28)), menses resumption (AOR = 4.9 95% CI: (2.92, 8.20)), sexual intercourse resumption (AOR = 7.1 95% CI: (4.03, 12.56)) and received postpartum family planning counseling (AOR = 3.2 95% (1.95, 5.28)) were the factors associated with Long-acting reversible contraception use.

Conclusion

This finding showed postpartum women’s long-acting reversible contraceptive use during the extended postpartum period was low. The factors significantly associated with extended postpartum modern contraceptive use were women’s age, being married, menses resumption, sexual intercourse resumption, and got postnatal family planning counseling. Strengthening Antenatal and postnatal counseling of postpartum family planning would improve long-acting reversible contraception use.
Livelihood assets’ influence on Ugandan farmers’ control practices for Banana Xanthomonas Wilt (BXW)
Authors: Pagnani Tiziana , Gotor Elisabetta , Kikulwe Enoch , Caracciolo Francesco
Published: September 2021

This study analyzes the influence of livelihood assets on Ugandan farmers’ decisions to control Banana Xanthomonas Wilt (BXW), a disease that has threatened banana production and the livelihoods of Ugandan farmers since 2001. The BXW control strategy is based on the simultaneous implementation of four cultural practices: de-budding, infected plant removal, disinfecting tools, and using clean planting materials. The Sustainable Rural Livelihood (SRL) framework represents a very useful theoretical architecture for examining the interplay between livelihood systems of rural Ugandan households and the external context. Empirically, this study applies a double-hurdle model with the base assumption that the two adoption decision processes (whether to adopt and the intensity of adoption of the cultural practices) are separate. Results indicate that the vulnerability context and the human, social, natural, and physical capitals are the factors that drive farmers to adopt the identified strategy. Farmers’ decisions about the extent of adoption are instead negatively influenced by natural capital and positively associated with social capital. These findings highlight the importance of supporting the improvement of livelihood assets to enable tailored support to farmers. It is particularly important to support the social and natural capitals that facilitate information exchange and provide critical resources for the adoption of the BXW control strategy.
Continuous diagnostic models for volume deficit in patients with acute diarrhea
Authors: Lee J. Austin , Qu Kexin , Gainey Monique , Kanekar Samika S. , Barry Meagan A. , Nasrin Sabiha , Alam Nur H. , Schmid Christopher H. , Levine Adam C.
Published: September 2021

Background

Episodes of acute diarrhea lead to dehydration, and existing care algorithms base treatment around categorical estimates for fluid resuscitation. This study aims to develop models for the percentage dehydration (fluid deficit) in individuals with acute diarrhea, to better target treatment and avoid the potential sequelae of over or under resuscitation.

Methods

This study utilizes data from two prospective cohort studies of patients with acute diarrhea in Dhaka, Bangladesh. Data were collected on patient arrival, including weight, clinical signs and symptoms, and demographic information. Consecutive weights were obtained to determine the true volume deficit of each patient. Data were entered into two distinct forward stepwise regression logistic models (DHAKA for under 5 years and NIRUDAK for 5 years and over).

Results

A total of 782 patients were included in the final analysis of the DHAKA data set, and 2139 were included in the final analysis of the NIRUDAK data set. The best model for the DHAKA data achieved an R2 of 0.27 and a root mean square error (RMSE) of 3.7 (compared to R2 of 0.06 and RMSE of 5.5 with the World Health Organization child care algorithm) and selected 6 predictors. The best performance model for the NIRUDAK data achieved an R2 of 0.28 and a RMSE of 2.6 (compared to R2 of 0.08 and RMSE of 4.3 with the World Health Organization adolescent/adult care algorithm) and selected 7 predictors with 2 interactions.

Conclusions

These are the first mathematical models for patients with acute diarrhea that allow for the calculation of a patient’s percentage dehydration (fluid deficit) and subsequent targeted treatment with fluid resuscitation. These findings are an improvement on existing World Health Organization care algorithms.
Progression of PTH Resistance in Autosomal Dominant Pseudohypoparathyroidism Type Ib Due to Maternal STX16 Deletions
Authors: Kiuchi Zentaro , Reyes Monica , Hanna Patrick , Sharma Anu , DeClue Terry , Olney Robert C , Tebben Peter , Jüppner Harald
Published: September 2021

Context

Maternally inherited STX16 deletions that cause loss of methylation at GNAS exon A/B and thereby reduce Gsα expression are the most frequent cause of autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP1B). Early identification of these disease-causing variants in the children of affected and unaffected female carriers would prompt treatment with calcium and calcitriol once parathyroid hormone (PTH) levels increase, thereby preventing hypocalcemia and associated complications.

Objective

This study aimed to determine when PTH and calcium abnormalities develop after birth if a STX16 deletion is inherited maternally.

Methods

Forty-four children of affected (n = 7) or unaffected (n = 7) females with a STX16 deletion were investigated for the presence of these variants. If a deletion was identified, measurement of PTH, calcium, phosphate, and thyrotropin (TSH) was advised.

Results

The STX16 deletion that causes AD-PHP1B was identified in 25 children. Pretreatment laboratory results were available for 19 of those cases. Elevated PTH levels were detected by 2 years of age, and these were progressively higher if laboratory testing was first performed after establishing the genetic defect later in life. Total serum calcium levels remained within normal limits until about 5 years of age. TSH levels showed no consistent rise over time.

Conclusion

Establishing whether a STX16 deletion is inherited from a female carrier of a disease-causing variant rapidly establishes the diagnosis of AD-PHP1B. Several years before overt hypocalcemia developed, PTH levels increased, thereby establishing the onset of PTH resistance. Our findings provide diagnostic guidance and when treatment with calcium and calcitriol should be considered in order to prevent hypocalcemia and associated sequelae.
Effects of the Affordable Care Act Dependent Coverage Mandate on Health Insurance Coverage for Individuals in Same-Sex Couples
Authors: Carpenter Christopher S. , Gonzales Gilbert , McKay Tara , Sansone Dario
Published: September 2021

A large body of research documents that the 2010 dependent coverage mandate of the U.S. Affordable Care Act was responsible for significantly increasing health insurance coverage among young adults. No prior research has examined whether sexual minority young adults also benefitted from the dependent coverage mandate despite previous studies showing lower health insurance coverage among sexual minorities. Our estimates from the American Community Survey, using difference-in-differences and event study models, show that men in same-sex couples aged 21–25 experienced a significantly greater increase in the likelihood of having any health insurance after 2010 than older, 27- to 31-year-old men in same-sex couples. This increase is concentrated among employer-sponsored insurance, and it is robust to permutations of periods and age groups. Effects for women in same-sex couples and men in different-sex couples are smaller than the associated effects for men in same-sex couples. These findings confirm the broad effects of expanded dependent coverage and suggest that eliminating the federal dependent mandate could reduce health insurance coverage among young adult sexual minorities in same-sex couples.
Sulfide metabolism and the mechanism of torpor
Authors: Jensen Birgitte S. , Fago Angela
Published: September 2021

Hibernation is a powerful response of a number of mammalian species to reduce energy during the cold winter season, when food is scarce. Mammalian hibernators survive winter by spending most of the time in a state of torpor, where basal metabolic rate is strongly suppressed and body temperature comes closer to ambient temperature. These torpor bouts are regularly interrupted by short arousals, where metabolic rate and body temperature spontaneously return to normal levels. The mechanisms underlying these changes, and in particular the strong metabolic suppression of torpor, have long remained elusive. As summarized in this Commentary, increasing evidence points to a potential key role for hydrogen sulfide (H2S) in the suppression of mitochondrial respiration during torpor. The idea that H2S could be involved in hibernation originated in some early studies, where exogenous H2S gas was found to induce a torpor-like state in mice, and despite some controversy, the idea persisted. H2S is a widespread signaling molecule capable of inhibiting mitochondrial respiration in vitro and studies found significant in vivo changes in endogenous H2S metabolites associated with hibernation or torpor. Along with increased expression of H2S-synthesizing enzymes during torpor, H2S degradation catalyzed by the mitochondrial sulfide:quinone oxidoreductase (SQR) appears to have a key role in controlling H2S availability for inhibiting respiration. Specifically, in thirteen-lined squirrels, SQR is highly expressed and inhibited in torpor, possibly by acetylation, thereby limiting H2S oxidation and causing inhibition of respiration. H2S may also control other aspects associated with hibernation, such as synthesis of antioxidant enzymes and of SQR itself.
Influence of an L-type SALMFamide neuropeptide on locomotory performance and muscle physiology in the sea cucumber Apostichopus japonicus
Authors: Ding Kui , Zhang Libin , Fan Xinhao , Zhuo Pengji , Feng Qiming , Zhang Shuangyan , Guo Xueying , Liu Xiang
Published: September 2021

Neuropeptides in the SALMFamide family serve as muscle relaxants in echinoderms and may affect locomotion, as the motor behavior in sea cucumbers involves alternating contraction and extension of the body wall, which is under the control of longitudinal muscle. We evaluated the effect of an L-type SALMFamide neuropeptide (LSA) on locomotory performance of Apostichopus japonicus. We also investigated the metabolites of longitudinal muscle tissue using ultra performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) to assess the potential physiological mechanisms underlying the effect of LSA. The hourly distance, cumulative duration and number of steps moved significantly increased in sea cucumbers in the fourth hour after injection with LSA. Also, the treatment enhanced the mean and maximum velocity by 9.8% and 17.8%, respectively, and increased the average stride by 12.4%. Levels of 27 metabolites in longitudinal muscle changed after LSA administration, and the increased concentration of pantothenic acid, arachidonic acid and lysophosphatidylethanolamine, and the altered phosphatidylethanolamine/phosphatidylcholine ratio are potential physiological mechanisms that could explain the observed effect of LSA on locomotor behavior in A. japonicus.
Allometry in desert ant locomotion (Cataglyphis albicans and Cataglyphis bicolor) – does body size matter?
Authors: Tross Johanna , Wolf Harald , Pfeffer Sarah Elisabeth
Published: September 2021

Desert ants show a large range of adaptations to their habitats. They can reach extremely high running speeds, for example, to shorten heat stress during foraging trips. It has recently been examined how fast walking speeds are achieved in different desert ant species. It is intriguing in this context that some species exhibit distinct intraspecific size differences. We therefore performed a complete locomotion analysis over the entire size spectrum of the species Cataglyphis bicolor, and we compared this intraspecific dataset with that of the allometrically similar species Cataglyphis albicans. Emphasis was on the allometry of locomotion: we considered the body size of each animal and analysed the data in terms of relative walking speed. Body size was observed to affect walking parameters, gait patterns and phase relationships in terms of absolute walking speed. Unexpectedly, on a relative scale, all ants tended to show the same overall locomotion strategy at low walking speeds, and significant differences occurred only between C. albicans and C. bicolor at high walking speeds. Our analysis revealed that C. bicolor ants use the same overall strategy across all body sizes, with small ants reaching the highest walking speeds (up to 80 body lengths s−1) by increasing their stride length and incorporating aerial phases. By comparison, C. albicans reached high walking speeds mainly by a high synchrony of leg movement, lower swing phase duration and higher stride frequency ranging up to 40 Hz.
Μελέτη αποτελεσμάτων κυκλικής εφαρμογής αντιμικροβιακών σχημάτων εμπειρικής θεραπείας εμπύρετης ουδετεροπενίας σε ασθενείς με αιματολογικά νοσήματα
Authors: Κοντοπίδου Φλώρα
Published: September 2021

ΕισαγωγήΗ εμπύρετη ουδετεροπενία για τους αιματολογικούς ασθενείς αποτελεί ένα κλινικό σύνδρομοεπείγουσας αντιμετώπισης που απαιτεί την άμεση χορήγηση κατάλληλης αντιμικροβιακήςθεραπείας. Η χορήγηση μη επαρκούς αντιμικροβιακής θεραπείας στα σηπτικά επεισόδια τωνουδετεροπενικών ασθενών έχει συσχετισθεί με υψηλή νοσηρότητα και θνητότητα των ασθενώναυτών όπως ακριβώς και των βαρέως πασχόντων ασθενών στις ΜΕΘ. Το cycling παρόλο πουέχει προταθεί ως μέτρο ελέγχου της μικροβιακής αντοχής η εφαρμογή του έχει καταλήξει σεαμφιλεγόμενα αποτελέσματα. Το cycling στην παρούσα μελέτη εφαρμόστηκε σε μία μικρήαιματολογική μονάδα με στόχο να ελέγξει τα επίπεδα της μικροβιακής αντοχής λόγω αύξησης τωννοσηλευομένων ασθενών με εμπύρετα επεισόδια ουδετεροπενίας και άρα αύξησης τηςκατανάλωσης των αντιμικροβιακών ευρέος φάσματος στο συγκεκριμένο κλινικό τμήμα.ΜεθοδολογίαΗ κυκλική εφαρμογή 4 αντιμικροβιακών σχημάτων ευρέος φάσματος εφαρμόστηκε σε μίααιματολογική μονάδα σε ασθενείς με εμπύρετη ουδετεροπενία για 3-5 μήνες το κάθε σχήμαΠραγματοποιήθηκαν δύο κύκλοι συνολικής διάρκειας 31 μηνών (2001-2003). Μελετήθηκε ηεπίδραση του cycling στην καταλληλότητα της αντιμικροβιακής αγωγής που χορηγήθηκε στουςασθενείς με εμπύρετη ουδετεροπενία, στην κλινική ανταπόκριση των ασθενών, στην εξέλιξη τηςμικροβιακής αντοχής και στον αποικισμό των ασθενών από πολυανθεκτικά παθογόνα.ΑποτελέσματαΚατά την διάρκεια της μελέτης νοσηλεύτηκαν στην κλινική αιματολογικοί ασθενείς που εμφάνισαν58 επεισόδια εμπύρετης ουδετεροπενίας εκ των οποίων τα 52 (90%) εισήχθησαν στην μελέτη. Ησυμμόρφωση στην εφαρμογή του πρωτοκόλλου κυμάνθηκε από 57%-100% και η συνολικήεπιτυχή ανταπόκριση των ασθενών στην αρχική χορηγούμενη αντιμικροβιακή θεραπέια ήταν 83%.Τα επίπεδα μικροβιακής αντοχής των Gram αρνητικών παθογόνων παρέμεινε σταθερή ενώ για τηνPseudomonas aeruginosa που αποτέλεσε το συχνότερο απομονωθέν παθογόνο τα επίπεδαμειώθηκαν στο τέλος της περιόδου εφαρμογής του προγράμματος. Κανένας από τους ασθενείς δεναποικίσθηκε (ορθικός αποικισμός) με πολυανθεκτικό στέλεχος. Η επίπτωση των Gram αρνητικών παθογόνων μειώθηκε τόσο στην κλινική όσο και στο υπόλοιπο νοσοκομείο ενώ των Gram θετικώνπαρέμεινε σταθερή στα χαμηλά αρχικά επίπεδα.ΣυμπεράσματαΤα αποτελέσματα της παρούσας μελέτης βασίζονται στα υψηλά επίπεδα χορήγησης κατάλληλήςεμπειρικής αντιμικροβιακής αγωγής και κλινικής ανταπόκρισης των ασθενών καθώς επίσης καιστην θετική επίδραση του cycling στην εξέλιξη της μικροβιακής αντοχής. Παρόλο το γεγονός ότι οιπερισσότερες μελέτες όπως και η παρούσα είναι σχετικά παλιές καταλήγουν στο ότι η εφαρμογήτου cycling σε αιματολογικές μονάδες είναι εφικτή χωρίς ανεπιθύμητες επιπτώσεις. Ο κατάλληλοςσχεδιασμός της εφαρμογής ενός προγράμματος cycling καθώς και η κατάλληλη επιλογή τωναντιβιοτικών που θα χορηγηθούν θα μπορούσε να μετατρέψει το συγκεκριμένο μέτρο σε ένααποτελεσματικό μέτρο κατά της ταχέως αυξανόμενης μικροβιακής αντοχής.
Η θεσμοποίηση της λειτουργίας της παραγωγής στην πρακτική της εταιρικής στρατηγικής
Authors: Καρφάκη Ελένη
Published: September 2021

Ένα από τα καίρια ζητήματα στο πεδίο της Στρατηγικής Διοίκησης είναι η διαμόρφωση της στρατηγικής η οποία μπορεί να καθορίσει την επιχειρηματική επιτυχία ή αποτυχία. Η διδακτορική διατριβή καταπιάνεται τη διαδικασία της στρατηγικής που αποσκοπεί στη θεωρητική και εμπειρική κατανόηση της φύσης των μηχανισμών που συνθέτουν τη διαδικασία αυτή. Προς την κατεύθυνση αυτή, αναλύει το ρόλο των αναδυόμενων στρατηγικών πρωτοβουλιών ως μηχανισμών που οδηγούν και νομιμοποιούν τα ενδιαφέροντα της παραγωγής στο στρατηγικό διάλογο της εταιρικής λήψης αποφάσεων. Το θεωρητικό υπόβαθρο της έρευνας συνίσταται στη θεώρηση της Στρατηγικής ως Πρακτικής (Strategy as Practice) μέσω της εστίασης στις πρακτικές που αναπτύσσουν οι συντελεστές της στρατηγικής καθώς αλληλοεπιδρούν για να προάγουν τα ενδιαφέροντά τους δημιουργώντας οριζόντιες σχέσεις με άλλες λειτουργίες και επικοινωνώντας τη στρατηγική τους σε κάθετες δομές. Αυτή η διερεύνηση πραγματοποιείται βάσει μιας προσέγγισης βασισμένης στην πρακτική (practice-based approach) προκειμένου να εξηγηθεί το ποιος, πώς και γιατί εμπλέκεται στον οργανωσιακό διάλογο για τη δημιουργία ενός κοινού πλαισίου συζήτησης για την προώθηση των στρατηγικών πρωτοβουλιών. Σε ανταπόκριση στην αδυναμία των υπαρχουσών προσεγγίσεων να παρέχουν ολιστικές ερμηνείες για το φαινόμενο, στη διατριβή αναπτύσσονται δύο ερμηνευτικά πλαίσια που βασίζονται στη Θεωρία Κοινωνικής Πρακτικής του Pierre Bourdieu και στη Θεωρία Δικτύου Συντελεστών. Ακολουθώντας μια παραγωγική συλλογιστική (deductive logic) στη μεθοδολογία έρευνας, τα δύο ερμηνευτικά αυτά πλαίσια επαληθεύονται μέσω μιας μοναδικής μελέτης περίπτωση. Συγκεκριμένα μελετάται η διαδικασία ευθυγράμμισης μιας στρατηγικής πρωτοβουλίας που ξεκινά από τη λειτουργία της παραγωγής και ταξιδεύει μέχρι το εταιρικό επίπεδο λήψης αποφάσεων μιας οργάνωσης παροχής εκπαιδευτικών υπηρεσιών. Συνολικά η ερευνητική μεθοδολογία επιβεβαιώνει τον επεξηγηματικό πλούτο που οι δύο προσεγγίσεις αξιώνουν να παρέχουν στο πεδίο διαμόρφωσης της στρατηγικής παραγωγής και προσφέρει νέες γνώσεις σχετικά με το ποιος, πώς και γιατί αναπτύσσει στρατηγικές πρωτοβουλίες αναδεικνύοντας το σπουδαίο ρόλο του πλαισίου δράσης και των τεχνουργημάτων στη διαμόρφωση της στρατηγικής. Θεωρητικά η διατριβή ενισχύει την προσπάθεια μελέτης της Στρατηγικής ως Πρακτικής και ειδικά στο πεδίο της στρατηγικής παραγωγής. Πρακτικά η νέα γνώση που προσφέρουν τα ερμηνευτικά πλαίσια μπορεί να αξιοποιηθεί στην παροχή συμβουλευτικής και να ενισχύσει τα στελέχη προς την πιο αποτελεσματική διαχείριση των στρατηγικών πρωτοβουλιών και τη διαμόρφωση πιο αποτελεσματικών στρατηγικών μέσω της αναγνώρισης του πολύπλοκου συγκείμενου δράσης.
Sovereign debt risk and financial markets
Authors: Μωράτης Γεώργιος
Published: September 2021

Η παρούσα διατριβή εκπονήθηκε με στόχο να διερευνήσει θέματα αποτίμησης του κινδύνου αθέτησης πιστωτικών ιδρυμάτων και του Δημοσίου των χωρών μελών της Ευρωζώνης, κατά την περίοδο της πρόσφατης παγκόσμιας χρηματοοικονομικής κρίσης και κρίσης χρέους στις χώρες του Ευρώ. Οι κρίσεις αυτές δημιούργησαν νέες και πολύπλοκες σχέσεις στις χρηματοπιστωτικές αγορές που όχι μόνο ανέδειξαν τα κενά στη διάρθρωση της Οικονομικής και Νομισματικής Ένωσης (ΟΝΕ), αλλά και συνέβαλαν στην ενδυνάμωση της αστάθειας των χρηματοπιστωτικών αγορών. Βασικό χαρακτηριστικό των νέων αυτών σχέσεων είναι η ενίσχυση της αλληλεξάρτησης του κινδύνου αθέτησης μεταξύ των χρηματοπιστωτικών ιδρυμάτων και των αντίστοιχων κρατών που οδήγησε στην ανατροφοδότηση του τραπεζικού και κρατικού πιστωτικού κινδύνου. Η σχέση αυτή αποκτά ιδιαίτερο ενδιαφέρον στην περίπτωση της Ευρωζώνης καθώς η κοινή νομισματική πολιτική αύξησε σημαντικά τον κίνδυνο μετάδοσης των διαταραχών από τις χώρες υπό διάσωση σε άλλες χώρες μέλη.
Statistical charge-based modeling of 1/f noise in standard and high-voltage MOS transistors
Authors: Μαυρεδάκης Νικόλαος
Published: September 2021

Στις μέρες μας, οι εφαρμογές αναλογικών και ολοκληρωμένων κυκλωμάτων πολύ υψηλών συχνοτήτων (RFIC) σχεδιάζονται αποκλειστικά με τεχνολογία CMOS. Εκτός από τη συμβατική CMOS τεχνολογία, η HV-MOS τεχνολογία χρησιμοποιείται επίσης ευρέως σε συγκεκριμένες εφαρμογές όπως στη βιομηχανία αυτοκινήτων, σε επιστημονικές και ιατρικές εφαρμογές και σε ηλεκτρονικά είδη ευρείας κατανάλωσης. Η απόδοση τόσο της CMOS όσο και της HVMOS σχεδίασης μπορεί να περιοριστεί από το θόρυβο χαμηλών συχνοτήτων (LFN) που γίνεται ιδιαίτερα σημαντικός σε σύγχρονες τεχνολογίες μιας και είναι αντιστρόφως ανάλογος με το μήκος του καναλιού. Η μέση τιμή και η μεταβλητότητα του θορύβου χαμηλών συχνοτήτων είναι εξαρτώμενες τόσο από την επιφάνεια όσο και από τις συνθήκες πόλωσης του τρανζίστορ. Η μεταβλητότητα αυξάνει όσο οι διαστάσεις της διάταξης μειώνονται ενώ παρόμοια συμπεριφορά παρουσιάζει και η μέση τιμή του θορύβου. Η ίδια συμπεριφορά μπορεί να παρατηρηθεί όσον αφορά την εξάρτηση της μεταβλητότητας του 1/f θορύβου από την πόλωση. Ο 1/f θόρυβος στα HV- MOSFETs αναμένεται να δημιουργείται από τις ίδιες αιτίες όπως και στα συμβατικά MOSFETs μιας και οι ίδιες αρχές λειτουργίας διέπουν και τα δύο είδη αυτών των MOS διατάξεων εξαιτίας της ύπαρξης της διεπαφής οξειδίου. Tο βασικό ερώτημα ήταν αν κάποιο παρόμοιο φαινόμενο παρατηρείται στην drift περιοχή. Η ανάλυση μας έδειξε ότι η επέκταση του οξιδίου της πύλης στην επιφάνεια της drift περιοχής, μπορεί να προκαλέσει 1/f θόρυβο. Εξαιτίας της σημαντικής επίδρασης του LFN σε προηγμένη σχεδίαση αναλογικών και RF κυκλωμάτων, η χρήση σωστών, βασισμένων στη φυσική, συμπαγών μοντέλων τόσο για τη μέση τιμή όσο και για την στατιστική συμπεριφορά του LFN έχει γίνει αναγκαία για τις ανάγκες προσομοίωσης θορύβου. Στα πλαίσια αυτής της διατριβής, ένα συμπαγές, βασισμένο στα φορτία, μοντέλο τόσο για τη μέση τιμή όσο και για την μεταβλητότητα του 1/f θορύβου αναπτύχθηκε και επικυρώθηκε τόσο για τη συμβατική CMOS τεχνολογία όσο και για την HV-MOS τεχνολογία για πρώτη φορά.