bluuebunny/crossref_metadata_2025 huggingface dataset:
Stochasticity invariance control in Pr1−x
Ca
x
MnO3 RRAM to enable large-scale stochastic recurrent neural networks
Authors: Saraswat Vivek , Ganguly Udayan
Published: December 2021

Emerging non-volatile memories have been proposed for a wide range of applications, from easing the von-Neumann bottleneck to neuromorphic applications. Specifically, scalable RRAMs based on Pr1−x
Ca
x
MnO3 (PCMO) exhibit analog switching have been demonstrated as an integrating neuron, an analog synapse, and a voltage-controlled oscillator. More recently, the inherent stochasticity of memristors has been proposed for efficient hardware implementations of Boltzmann machines. However, as the problem size scales, the number of neurons increases and controlling the stochastic distribution tightly over many iterations is necessary. This requires parametric control over stochasticity. Here, we characterize the stochastic set in PCMO RRAMs. We identify that the set time distribution depends on the internal state of the device (i.e., resistance) in addition to external input (i.e., voltage pulse). This requires the confluence of contradictory properties like stochastic switching as well as deterministic state control in the same device. Unlike ‘stochastic-everywhere’ filamentary memristors, in PCMO RRAMs, we leverage the (i) stochastic set in negative polarity and (ii) deterministic analog Reset in positive polarity to demonstrate 100× reduced set time distribution drift. The impact on Boltzmann machines’ performance is analyzed and as opposed to the ‘fixed external input stochasticity’, the ‘state-monitored stochasticity’ can solve problems 20× larger in size. State monitoring also tunes out the device-to-device variability effect on distributions providing 10× better performance. In addition to the physical insights, this study establishes the use of experimental stochasticity in PCMO RRAMs in stochastic recurrent neural networks reliably over many iterations.
Inappropriate prescribing: hazards and solutions
Authors: Petrovic Mirko , O’Mahony Denis , Cherubini Antonio
Published: December 2021

With population ageing, the number of older people is growing, which results in increasing number of people with multimorbidity and related polypharmacy. Polypharmacy in its turn leads to drug-related problems (DRPs) and potentially inappropriate prescribing (IP) in older people. In this commentary, susceptibility of older people to DRPs due to changes in pharmacokinetics and pharmacodynamics, plurality of prescribing physicians, inadequate consideration of patients’ characteristics, polypharmacy and its consequences such as prescribing cascades, drug interactions and potentially IP have been discussed respectively. Consecutively, identifying DRPs and optimizing of IP, including drug reconciliation, application of criteria for identifying and preventing IP, implementation of computer-based prescribing systems, and comprehensive geriatric assessment and management have been elaborated as well. One of the main challenges regarding appropriate and tailored prescribing in older people is to evaluate whether the expected benefits of pharmacotherapy are bigger than the risks in a population with multimorbidity, decreased tolerance to vulnerability and limited life expectancy. Comprehensive geriatric assessment enables informed prescribing decisions in the context of such variables. A challenge for future research is how to integrate important clinical information obtained by existing methods into a comprehensive and wide-reaching approach targeting all potential factors involved in causing DRPs. Good prescribing in late life accommodates the needs of older patients with multimorbidity. Individualized, interactive, multidisciplinary, and multifaceted approach to geriatric pharmacotherapy should be promoted and encouraged. How to optimize pharmacological prescription in complex older patients is a major legacy of geriatrics to contemporary medicine/medical practice.
Secondhand Smoke Exposure During Childhood and Cancer Mortality in Adulthood Among Never Smokers: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk
Authors: Teramoto Masayuki , Iso Hiroyasu , Wakai Kenji , Tamakoshi Akiko
Published: December 2021

We examined whether secondhand smoke exposure during childhood was associated with cancer mortality in adulthood among never smokers. In the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, we analyzed data from 45,722 Japanese lifetime nonsmokers aged 40–79 years with no history of cancer at baseline (1988–1990) who had completed a lifestyle questionnaire, including information on the number of family members who had smoked at home during their childhood (0, 1, 2, or ≥3 family members). A Cox proportional hazards model and competing-risks regression were used to calculate multivariable hazard ratios and subdistribution hazard ratios with 95% confidence intervals for overall and site-specific cancer mortality according to the number of family members who smoked during the participant’s childhood, after adjusting for potentially confounding factors. During a median follow-up period of 19.2 years, a total of 2,356 cancer deaths were documented. Secondhand smoke exposure was positively associated with the risk of mortality from pancreatic cancer in adulthood; the multivariable hazard ratio for having 3 or more family members who smoked (as compared with none) was 2.32 (95% confidence interval: 1.14, 4.72). Associations were not evident for total cancer risk or risk of other types of smoking-related cancer. In this study, secondhand smoke exposure during childhood was associated with an increased risk of pancreatic cancer mortality in adulthood.
Comethyl: a network-based methylome approach to investigate the multivariate nature of health and disease
Authors: Mordaunt Charles E , Mouat Julia S , Schmidt Rebecca J , LaSalle Janine M
Published: December 2021

Health outcomes are frequently shaped by difficult to dissect inter-relationships between biological, behavioral, social and environmental factors. DNA methylation patterns reflect such multivariate intersections, providing a rich source of novel biomarkers and insight into disease etiologies. Recent advances in whole-genome bisulfite sequencing enable investigation of DNA methylation over all genomic CpGs, but existing bioinformatic approaches lack accessible system-level tools. Here, we develop the R package Comethyl, for weighted gene correlation network analysis of user-defined genomic regions that generates modules of comethylated regions, which are then tested for correlations with multivariate sample traits. First, regions are defined by CpG genomic location or regulatory annotation and filtered based on CpG count, sequencing depth and variability. Next, correlation networks are used to find modules of interconnected nodes using methylation values within the selected regions. Each module containing multiple comethylated regions is reduced in complexity to a single eigennode value, which is then tested for correlations with experimental metadata. Comethyl has the ability to cover the noncoding regulatory regions of the genome with high relevance to interpretation of genome-wide association studies and integration with other types of epigenomic data. We demonstrate the utility of Comethyl on a dataset of male cord blood samples from newborns later diagnosed with autism spectrum disorder (ASD) versus typical development. Comethyl successfully identified an ASD-associated module containing regions mapped to genes enriched for brain glial functions. Comethyl is expected to be useful in uncovering the multivariate nature of health disparities for a variety of common disorders. Comethyl is available at github.com/cemordaunt/comethyl with complete documentation and example analyses.
The American Law Institute’s Restatement of the Law: Bastion, Bridge and Behemoth
Authors: Peters Anne
Published: December 2021

This article analyses the repercussions of restating foreign relations law for international law in the current constellation of backlash, or at least fatigue, with international law and global governance. Foreign relations law – consolidated, shaped and strengthened by the exercise of restating it – partly erects a bastion against international law and partly builds bridges between international law and domestic law. The foreign relations law of a powerful state such as the USA, in particular, risks marginalizing or even swallowing up international law. The article discusses four possible strategies to mitigate or counteract that ‘Behemoth’ tendency – namely, the normalization of foreign relations law, more intense restating exercises in international law proper, the elaboration of restatements of other countries’ foreign relations law and, finally, multi-perspectivism. The latter strategy involves seeing foreign relations law through the eyes of differently situated law appliers, notably by contemplating the consequences of the stated rules on other states and by comparing different nations’ foreign relations laws. The danger of US foreign relations law becoming the Behemoth of international law can be best contained by espousing such deliberate multi-perspectivism when designing, restating and interpreting it.
Ideal Men and Dream Women: Computer Matchmaking in twen during the West German Sex Wave, 1967–1970
Authors: Cincotta Natalie R
Published: December 2021

Between 1967 and 1970, the West German youth magazine twen embarked on an ambitious experiment to match young heterosexual pairs using computer programming. Named Rendezvous, the program emerged during a moment of particular promise and transformation in West German history. The so-called ‘sex wave’, an emphasis on self-discovery and the reconfiguration of social relationships, had produced both new possibilities and pressures for how young West Germans should ‘get to know’ each other and what they should find meaningful in their romantic relationships. Rendezvous promised to take the guesswork and disappointment out of finding an ideal partner through a rational, scientific assessment of habits, attitudes and desires. This article uses Rendezvous as a lens to examine early interactions between technology, media cultures and value change long before the internet age. Through an analysis of questionnaires, first-person accounts and photo reports, the article argues that Rendezvous evidences the centrality of mass media to the reorganization of courting and romance around notions of personal fulfillment and self-discovery during the late 1960s.
Robust, ecological–economic multispecies management of Central Baltic fishery resources
Authors: Voss Rudi , Quaas Martin , Neuenfeldt Stefan
Published: December 2021

The Baltic fisheries are in distress. In the Central Baltic, fisheries management is challenged by reduced cod stock productivity, and altered species interactions. Here, we use an age-structured, ecological–economic multispecies model, which includes latest biological and economic knowledge, to advance our understanding of optimal fisheries management and related trade-offs between user groups under such altered conditions. We contribute to the scientific discussion (i) by showing that the economic importance and optimal stock size of cod largely decreased under prevailing conditions, while clupeids increased in importance. (ii) We challenge the current MSY management objective in a multispecies setting (MMSY) and suggest that an economic multispecies management objective (MMEY) might be more useful for setting future management targets. (iii) We identify new trade-offs and synergies by including a consumer perspective: There is a win–win situation for ecological conservation, and profits in the fishery, while fishery management faces trade-offs between these two on the one hand, and consumer surplus on the other hand. (iv) Finally, we suggest an easy to implement new management approach, called robust management, which is capable of better dealing with variability and time-trends in recruitment, as observed for cod, in order to safeguard the Central Baltic fishery resources.
MCH-Based Semiochemical Repellents for Protecting Engelmann Spruce Trees From Dendroctonus rufipennis (Coleoptera: Curculionidae)
Authors: Audley Jackson P , Fettig Christopher J , Steven Munson A , Blackford Darren C , Mortenson Leif A , Mafra-Neto Agenor
Published: December 2021

Spruce beetle, Dendroctonus rufipennis Kirby (Coleoptera: Curculionidae), is a lethal pest of spruce trees in North America. Despite decades of research, a semiochemical repellent that consistently and effectively protects spruce trees remains elusive. We evaluated the efficacy of 3-methyl-2-cyclohexen-1-one (MCH) in a proprietary, volatile compound release technology (SPLAT) alone and with two adjuvants, Acer kairomone blend (AKB) and acetophenone + green leaf volatiles (PLUS) to protect individually treated Picea engelmannii Parry ex. Engelm. (Pinales: Pinaceae), and Pi. engelmannii within 11.3-m radius of the individually treated trees from colonization and mortality attributed to D. rufipennis in western Wyoming. Ninety-one Pi. engelmannii were baited with frontalin and randomly assigned to one of seven treatments (n = 13): 3.5 g of MCH applied as SPLAT MCH (SPLAT3.5), 3.5AKB, 3.5PLUS, 7 g of MCH applied as SPLAT MCH (SPLAT7), 7AKB, 7PLUS, and baited control (bait only). All repellents except SPLAT3.5 and SPLAT7 significantly reduced colonization of individually treated Pi. engelmannii compared to the baited control. 3.5PLUS, 7AKB, and 7PLUS reduced colonization most effectively, and all repellents significantly reduced mortality of individually treated Pi. engelmannii compared to the baited control. All repellents also significantly reduced colonization and mortality of neighboring Pi. engelmannii.
Can Good Products Drive Out Bad? A Randomized Intervention in the Antimalarial Medicine Market in Uganda
Authors: Björkman Nyqvist Martina , Svensson Jakob , Yanagizawa-Drott David
Published: December 2021

How can quality be improved in markets in developing countries, which are known to be plagued by substandard and counterfeit (“fake”, in short) products? We study the market for antimalarial drugs in Uganda, where we randomly assign entry of a retailer (non-governmental organization (NGO)) providing a superior product—an authentic drug priced below the market—and investigate how incumbent firms and consumers respond. We find that the presence of the NGO had economically important effects. Approximately one year after the new market actor entered, the share of incumbent firms selling fake drugs dropped by more than 50% in the intervention villages, with higher quality drugs sold at significantly lower prices. Household survey evidence further shows that the quality improvements were accompanied by consumers expecting fewer fake drugs sold by drug stores. The intervention increased use of the antimalarial drugs overall. The results are consistent with a simple model where the presence of a seller committed to high quality, as opposed to an average firm, strengthens reputational incentives for competing firms to improve quality in order to not be forced out of the market, leading to “good driving out bad”.
The Epigenetic Regulator Jumonji Domain-Containing Protein 6 (JMJD6) Is Highly Expressed but Not Prognostic in IDH-Wildtype Glioblastoma Patients
Authors: Rosager Ann Mari , Dahlrot Rikke H , Sørensen Mia D , Bangsø Julie A , Hansen Steinbjørn , Kristensen Bjarne W
Published: December 2021

Patients with IDH-wildtype glioblastoma (GBM) generally have a poor prognosis. However, there is an increasing need of novel robust biomarkers in the daily clinico-pathological setting to identify and support treatment in patients who become long-time survivors. Jumonji domain-containing protein 6 (JMJD6) is involved in epigenetic regulation of demethylation of histones and has been associated with GBM aggressiveness. We investigated the expression and prognostic potential of JMJD6 tumor fraction score in 184 IDH-wildtype GBMs. Whole-slides were double-stained with an antibody against JMJD6 and an exclusion-cocktail consisting of 4 antibodies (CD31, SMA, CD45, and Iba-1), enabling evaluation of tumor cells only. Stainings were quantified with a combined software- and scoring-based approach. For comparison, IDH-mutated WHO grade II, III and IV astrocytic gliomas were also stained, and the JMJD6 tumor fraction score increased with increasing WHO grade, although not significantly. In multivariate analysis including age, gender, performance status and post-surgical treatment high JMJD6 tumor fraction score was associated with longer overall survival in IDH-wildtype GBMs (p = 0.03), but the effect disappeared when MGMT promoter status was included (p = 0.34). We conclude that JMJD6 is highly expressed in IDH-wildtype GBM but it has no independent prognostic value.
A high-resolution investigation of the multiphase ISM in a galaxy during the first two billion years
Authors: Dye S , Eales S A , Gomez H L , Jones G C , Smith M W L , Borsato E , Moss A , Dunne L , Maresca J , Amvrosiadis A , Negrello M , Marchetti L , Corsini E M , Ivison R J , Bendo G J , Bakx T , Cooray A , Cox P , Dannerbauer H , Serjeant S , Riechers D , Temi P , Vlahakis C
Published: December 2021

We have carried out the first spatially resolved investigation of the multiphase interstellar medium (ISM) at high redshift, using the z = 4.24 strongly lensed submillimetre galaxy H-ATLASJ142413.9+022303 (ID141). We present high-resolution (down to ∼350 pc) ALMA observations in dust continuum emission and in the CO(7–6), $\rm H_2O (2_{1,1} - 2_{0,2})$, [C i] (1–0), and [C i] (2–1) lines, the latter two allowing us to spatially resolve the cool phase of the ISM for the first time. Our modelling of the kinematics reveals that the system appears to be dominated by a rotationally-supported gas disc with evidence of a nearby perturber. We find that the [C i] (1–0) line has a very different distribution to the other lines, showing the existence of a reservoir of cool gas that might have been missed in studies of other galaxies. We have estimated the mass of the ISM using four different tracers, always obtaining an estimate in the range of $\rm 3.2{\!-\!}3.8 \times 10^{11}\ M_{\odot }$, significantly higher than our dynamical mass estimate of $\rm 0.8{\!-\!}1.3 \times 10^{11}\ M_{\odot }$. We suggest that this conflict and other similar conflicts reported in the literature is because the gas-to-tracer ratios are ≃4 times lower than the Galactic values used to calibrate the ISM in high-redshift galaxies. We demonstrate that this could result from a top-heavy initial mass function and strong chemical evolution. Using a variety of quantitative indicators, we show that, extreme though it is at z = 4.24, ID141 will likely join the population of quiescent galaxies that appears in the Universe at z ∼ 3.
US201 Study: A Phase 2, Randomized Proof-of-Concept Trial of Favipiravir for the Treatment of COVID-19
Authors: Finberg Robert W , Ashraf Madiha , Julg Boris , Ayoade Folusakin , Marathe Jai G , Issa Nicolas C , Wang Jennifer P , Jaijakul Siraya , Baden Lindsey R , Epstein Carol
Published: December 2021

Background

Favipiravir is used to treat influenza, and studies demonstrate that it has antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods

We performed a randomized, open-label, multicenter, phase 2 proof-of-concept trial of favipiravir in hospitalized adult patients with polymerase chain reaction (PCR)–positive coronavirus disease 2019 (COVID-19). Patients were randomized to standard of care (SOC) or favipiravir treatment (1800mg per os twice a day [b.i.d.] on day 1, followed by 1000mg b.i.d. for 13 days). The primary end point was time to viral clearance on day 29.

Results

Fifty patients were enrolled and stratified by disease severity (critical disease, severe disease, or mild to moderate disease). Nineteen patients were censored from the event of viral clearance based on being SARS-CoV-2 PCR-negative at the study outset, being PCR-positive at day 29, or because of loss to follow-up. Data from the 31 remaining patients who achieved viral clearance show enhanced viral clearance in the favipiravir group compared with the SOC group by day 29, with 72% of the favipiravir group and 52% of the SOC group being evaluable for viral clearance through day 29. The median time to viral clearance was 16.0 days (90% CI, 12.0 to 29.0) in the favipiravir group and 30.0 days (90% CI, 12.0 to 31.0) in the SOC group. A post hoc analysis revealed an effect in the subgroup of patients who were neutralizing antibody–negative at randomization. Treatment-emergent adverse events were equally distributed between the groups.

Conclusions

We demonstrate that favipiravir can be safely administered to hospitalized adults with COVID-19 and believe that further studies are warranted.

ClinicalTrials.gov registration

NCT04358549.
STUDY ON THE INFLUENCE OF DRY DENSITY AND PARTICLE SIZE FRACTAL DISTRIBUTION ON THE RADON CONTROL PERFORMANCE OF OVERLYING SOIL IN URANIUM TAILINGS POND
Authors: Zhang Tiejun , Li Xiangyang , Hong Changshou , Liu Xiaolu , Wang Hong , Liu Yong
Published: December 2021

In order to explore the influence of dry density and particle size fractal distribution on the radon control performance of overlying soil in uranium tailings pond, overlying soil samples with different particle size fractal dimension and dry density were prepared for radon exhalation experiments. According to the principle of radon generation and diffusion, a set of radon measuring device was designed independently. In addition, the radon concentration on the surface of different overlying soil layers was measured by local static method, and the radon exhalation rate was further calculated. The relationship between radon exhalation law, dry density and fractal dimension of overlying soil was studied by correlation analysis method. Furthermore, a piecewise linear function between radon exhalation rate, dry density and fractal dimension was constructed. Then, the average value of the experimental data was compared with the calculated results. Results show that: at the same dry density and different fractal dimension, the radon exhalation rate decreased with the increase of fractal dimension. When the fractal dimension increased to a certain value, the radon exhalation rate tended to be stable. At the same fractal dimension and different dry density, the radon exhalation rate decreased with the increase of dry density. The calculated results of piecewise linear function were relatively close to the experimental data, which verified the practicability of the formula.
Management of anal cancer
Authors: Pullen Richard L.
Published: December 2021

This type of cancer is usually linked with human papilloma virus. Here's what you need to know about staging, treatment, and caring for patients receiving chemotherapy, radiation, and immunotherapy.
The Reliability of Postoperative Radiographic Matta Grading for Quality of Reduction of Acetabular Fractures
Authors: Mudawi Aiman , Salameh Motasem , Ahmed Abdulaziz F. , Mahmoud Shady , Alhammoud Abduljabbar , Abousamhadaneh Maamoun , Ahmed Ghalib
Published: December 2021

Objectives:

To assess the reliability of the postoperative radiographic Matta grading for quality of reduction of acetabular fractures.

Design:

An inter-reliability and intrareliability study.

Setting:

Level I trauma center.

Participants:

15 independent observers of different levels of experience who evaluated 115 sets of postoperative acetabulum radiographs in 35 consecutive patients with displaced acetabular fractures between January 2017 and January 2019.

Main Outcome Measurements:

To assess the interobserver and intraobserver reliability of Matta radiographic grading for postoperative quality of reduction of acetabular fractures.

Results:

The overall interobserver agreement was excellent among all groups with an average absolute intraclass correlation coefficient (ICC) of 0.91 (95% CI 0.93–0.97). When stratifying the agreement based on experience, the orthopaedic trauma fellow subgroup had the highest rate with an ICC of 0.92. The overall intraobserver agreement was good with an ICC of 0.81 (95% CI 0.74–0.85).

Conclusion:

The Matta radiographic grading was a reliable tool for the evaluation of quality of reduction after surgical fixation of acetabular fractures with excellent interobserver and good intraobserver reliabilities among different levels of observers.
Endoscopic characteristics in predicting prognosis of biopsy-diagnosed gastric low-grade intraepithelial neoplasia
Authors: Zou Long , Jiang Qingwei , Guo Tao , Wu Xi , Wang Qiang , Feng Yunlu , Zhang Shengyu , Fang Weigang , Zhou Weixun , Yang Aiming
Published: December 2021

Background:

Endoscopic biopsy can underestimate gastric malignancies as low-grade intraepithelial neoplasia (LGIN). Definitively diagnosed LGIN would progress. This study aimed to evaluate predictive factors to identify malignancies misdiagnosed as LGIN by biopsy and LGIN at high risk of progression.

Methods:

The clinical records of patients diagnosed with gastric LGIN by endoscopic biopsy who underwent at least two endoscopies during the first year of follow-up between 2007 and 2017 were retrospectively collected. Three endoscopists reviewed photographs of the initial endoscopy, described lesion characteristics, and made endoscopic diagnoses. Logistic regression was used to analyze predictors to identify malignancies underestimated as LGIN. A receiver operating characteristic curve was used to evaluate the diagnostic accuracy of these predictors. Patient clinical outcomes of follow-up >1 year were collected. Kaplan–Meier estimates with log-rank tests and Cox proportional hazards regression were used to analyze predictors of progression.

Results:

Overall, 48 of 182 (26.4%) patients were proven to have malignancies. A single lesion, a large lesion size, and marked intestinal metaplasia (IM) were independent predictors of initially misdiagnosed malignancies. The area under the curve of these predictors was 0.871, with a sensitivity of 68.7% and specificity of 92.5%. Twelve of 98 patients (12.2%) progressed during the 33-month median follow-up period. A whitish appearance, irregular margins, marked IM, and histological diagnosis of LGIN more than twice within the first year were predictors for progression.

Conclusions:

Lesions diagnosed as LGIN by biopsy with marked IM and other predictors above should be prudently treated for high potential to be malignancies or progress. Endoscopic follow-up with repeated biopsies within the first year is recommended.
Development and Reliability of the Physical Therapy Healthy Lifestyle Appraisal: A New Assessment Tool to Guide Behavior Change
Authors: Ingman MarySue , Bezner Janet R. , Black Beth , Vaughan Phillip W.
Published: December 2021

Purpose:

Physical therapists are well positioned to encourage their patients to live a healthy lifestyle. Physical therapists report barriers that limit their ability to practice health promotion counseling with their patients including the availability of a brief tool to gather information about their patient's current level of activity related to specific health behaviors. The purpose of this study was to describe the development and testing of the Physical Therapy Healthy Lifestyle Appraisal (PTHLA).

Methods:

The PTHLA is a patient self-report questionnaire that assesses stage of change, importance of changing, and confidence in engaging in 6 health behaviors. Physical Therapy Healthy Lifestyle Appraisal version 1 (106 items) was designed to compare different constructs for measuring stage of change and confidence in engaging in health behaviors. After pilot testing, 3 versions were tested to arrive at the 18 item PTHLA-version 3. Physical therapy patients in outpatient clinics in Michigan, Minnesota, and Texas were recruited for this multiphase study (version 1 n = 60, version 2 n = 65, and version 3 n = 28).

Results:

Physical Therapy Healthy Lifestyle Appraisal version 3 consists of 3 questions for each of 6 health behavior domains; a 3-option ordinal question for assessing stage of change and 11-point rulers for assessing importance of engaging in the behavior and confidence in engaging in the behavior. Unique items from version 1 and version 2 were retained in PTHLA-version 3, whereas those items that were somewhat redundant were excluded. Behavioral definitions for the “sleep” and “stress” domains were the only changes made from the first to the second versions. Across samples and behavioral domains, scores for the 18 items generally displayed satisfactory-to-high test–retest reliabilities (Cohen κ

w
= 0.56–1.00, mean = 0.76; Spearman ρ = 0.53–1.00, mean = 0.77; intraclass correlation coefficient = 0.39–1.00, mean = 0.74). Confidence in behavior ruler scores displayed satisfactory-to-high convergent correlations with scores from lengthier multiple-item confidence in behavior measures (Pearson r validity coefficients = 0.33–0.90, mean = 0.63). The three-option stage of change items demonstrated satisfactory convergent validity with scores on the stage of change ruler (Pearson r validity coefficients = 0.16–0.86, mean = 0.61).

Conclusions:

The PTHLA-version 3 is a reliable and efficient tool for PT practice developed by physical therapists with expertise in prevention, health promotion, and wellness. Physical therapists can use the information provided from the PTHLA to initiate conversations about behavior change with their patients. Understanding the patient's current stage of change, level of interest in changing the behavior, and confidence for changing the behavior is important information for the PT to ensure a productive and respectful conversation about behavior change.
Association of oral contraceptives and tubal ligation with antimüllerian hormone
Authors: Langton Christine R. , Whitcomb Brian W. , Purdue-Smithe Alexandra C. , Sievert Lynnette L. , Hankinson Susan E. , Manson JoAnn E. , Rosner Bernard A. , Bertone-Johnson Elizabeth R.
Published: December 2021

Objective:

Oral contraceptives (OCs) and tubal ligation are commonly used methods of contraception that may impact ovarian function. Few studies have examined the association of these factors with antimüllerian hormone (AMH), a marker of ovarian aging.

Methods:

We examined the association of OC use and tubal ligation with AMH in the Nurses’ Health Study II prospective cohort among a subset of 1,420 premenopausal participants who provided a blood sample in 1996-1999. History of OC use and tubal ligation were reported in 1989 and updated every 2 years until blood collection. We utilized generalized linear models to assess whether mean AMH levels varied by duration of and age at first use of OCs and history, age, and type of tubal ligation.

Results:

In multivariable models adjusted for smoking, reproductive events, and other lifestyle factors, we observed a significant, inverse association between duration of OC use and mean AMH levels (P for trend = 0.036). Compared to women without a tubal ligation, AMH levels were significantly lower when the procedure included a clip, ring, or band (1.04 ng/ml vs 1.72 ng/ml, P < 0.01). AMH levels were not associated with age at first use of OCs or age at tubal ligation.

Conclusions:

Our analysis found an association between duration of OC use and certain types of tubal ligation with mean AMH levels. Further research is warranted to confirm the long-term association of these widely used contraceptive methods with AMH.

Video Summary:

http://links.lww.com/MENO/A860.
Sinus headache: changing the treatment paradigm
Authors: Jang David W. , Godley Frederick A. , Hachem Ralph Abi
Published: December 2021

Purpose of review

Although the majority of patients with sinus headache do not have rhinosinusitis, many patients will unnecessarily undergo work-up and treatment for rhinosinusitis. This leads to a significant cost burden to the healthcare system. In the era of value-based care, more effective management paradigms need to be developed for sinus headache.

Recent findings

Recent efforts to classify nonrhinogenic headache, namely the International Classification of Orofacial Pain, have served as an important step in advancing our understanding of this heterogeneous condition. In addition, a review of the literature points to certain clinical features that may allow for the identification of nonrhinogenic headache based on history.

A greater understanding of nonrhinogenic headache as well as innovative tools to differentiate rhinogenic from nonrhinogenic headache are needed to change the paradigm in the management of patients with sinus headache.
Tick Paralysis Case Series
Authors: Pontiff Kristen , Woodward Christopher , McMahon Pamela
Published: December 2021

Objectives

The aims of the study were to identify and to describe cases of pediatric tick paralysis presenting to an emergency department in southern Louisiana during an 11-year period.

Methods

We conducted a retrospective chart review of patients aged 0 to 18 years with a diagnostic code of toxic effect of venom, tick-borne viral encephalitis, Guillain-Barré syndrome, acute infective polyneuritis, or abnormality of gait from July 2005 to June 2016. Data were collected on visit month, patient age, race and sex, tick's attachment site, location of tick removal, symptoms and length of symptoms, initial diagnosis, time to appropriate diagnosis, and hospital length of stay.

Results

Nine patients aged 2 to 10 years presented with lower limb weakness and varying degrees of upper extremity ataxia or paralysis, areflexia, dysarthria, diplopia, or petechia. Five cases were accurately and rapidly diagnosed; 4 cases involved a delay in accurate diagnosis. Treatment of the misdiagnosed cases ranged from septic workup to neurologic workup, including magnetic resonance imaging. The tick was discovered by the patients' relative in 4 cases, by a primary care or emergency care physician at another facility in 3 cases, and by 1 of our emergency care physicians in 2 patients.

Conclusions

The incidence of tick paralysis in southern Louisiana is unknown. However, our case series indicates that it is likely higher than expected. Although most cases in our facility were quickly diagnosed and treated through tick removal, delayed diagnosis results in unnecessary tests, procedures, and medical costs. All of our cases fully recovered after tick removal.
Impact of CYP2B6 genotype, tuberculosis therapy, and formulation on efavirenz pharmacokinetics in infants and children under 40 months of age
Authors: Nikanjam Mina , Tran Lana , Chadwick Ellen G. , Bwakura-Dangarembizi Mutsa , Bolton Moore Carolyn , Samson Pearl , Spector Stephen A. , Chakhtoura Nahida , Jean-Philippe Patrick , Frenkel Lisa , Zimmer Bonnie , Benns Alex , Libous Jennifer , Capparelli Edmund V.
Published: December 2021

Objective:

Dosing efavirenz (EFV) in children less than 3 years of age is challenging due to large variability in drug levels. This study evaluated differences in pharmacokinetics with tuberculosis (TB) therapy, formulation, age, and CYP2B6 genotype.

Design:

Pharmacokinetic data from three IMPAACT/PACTG studies (P382, P1021, and P1070) for children initiating therapy less than 40 months of age were evaluated.

Methods:

Pharmacokinetic data were combined in a population pharmacokinetic model. Exposure from the 2-week pharmacokinetic visit was compared with changes in viral RNA between the Week 0 and Week 4 visits.

Results:

The model included 103 participants (19 on TB therapy). CYP2B6 516 genotype information was available for 82 participants (TT: 15, GT: 28, GG: 39). Median age at the first pharmacokinetic visit was 17.0 months (range: 2.0–39.0 months). Liquid formulation led to a 42% decrease in bioavailability compared with opened capsules. TB therapy (isoniazid and rifampin) led to a 29% decreased clearance, however Monte Carlo simulations demonstrated the majority of participants on TB therapy receiving standard EFV dosing to be in the target area under the curve range. Clearance was 5.3-fold higher for GG than TT genotype and 3.3-fold higher for GT than TT genotype. Age did not have a significant effect on clearance in the final model. Initial viral RNA decay was lower for patients in the lowest quartile of exposures (area under the curves) than for higher quartiles (P = 0.013).

Conclusion:

EFV dosing should account for CYP2B6 516 genotype and formulation, but does not require adjustment for concurrent TB therapy.
Surgical Guides and Prebent Titanium Improve the Planning for the Treatment of Dentofacial Deformities Secondary to Condylar Osteochondroma
Authors: Zhu Zhaokun , He Ze , Tai Yue , Liu Yao , Liu Hanghang , Luo En
Published: December 2021

Purpose:

To investigate current Computer-Aided Design and Computer-Aided Manufacturing (CAD/CAM) technologies applied in the treatment of dentofacial deformities secondary to condylar osteochondroma and introduce a modified method with additional pre-bent titanium miniplates to improve the accuracy of operation.

Methods:

Literature review about the application of CAD/CAM in the treatment of condylar osteochondroma and secondary dentofacial deformities was conducted. And 8 patients with condylar osteochondroma and secondary dentofacial deformities were treated by the CAD/CAM cutting and drilling surgical guides as well as pre-bent titanium miniplates. Pre- and post-operative 3D-cephalometric measurement were recorded and the difference between virtual simulation and postoperative modeling images was measured. Follow-up and radiographic examinations were performed.

Results:

A total of 17 studies (including 216 patients) about the application of CAD/CAM in the treatment of dentofacial deformities secondary to condylar osteochondroma have been reported since 2010, including the 8 present patients. In our study, all patients were satisfied with the surgical outcome, without obvious relapse or evidence of temporomandibular joint disorder or other complications during follow-up; all patients avoided condylar reconstruction and sagittal split of ramus osteotomy on the ipsilateral mandible side. Comparison between simulated plans and actual postoperative outcomes showed surgical simulation plan was accurately transferred to the actual surgery.

Conclusions:

The application of CAD/CAM cutting and drilling guides as well as pre-bent titanium plates could achieve more accurate and favorable outcomes, improving the clinical planning and surgical execution for patients with condylar osteochondroma and secondary dentofacial deformities.
Socioeconomic Factors Impact the Timing of Surgical Repair for Craniosynostosis - A Regional and National Assessment
Authors: Keyho Ryan J. , Cepeda Alfredo , Greives Matthew R. , Nguyen Phuong D.
Published: December 2021

Introduction:

Timing of repair for patients with craniosynostosis are usually categorized into early “minimally invasive” surgeries such as strip craniotomy (SC), whereas those presenting later undergoing traditional cranial vault remolding (CVR). The impact that sociodemographic and socioeconomic disparities have on time to presentation for craniosynostosis and treatment is unknown. Herein, we examined sociodemographic and socioeconomic factors among a heterogenous patient population at a single institution who underwent craniosynostosis repair and compared this cohort to a national database.

Methods:

A retrospective review of patients at UTHealth who underwent craniosynostosis repair from 2016 to 2020 was performed. The patients were divided into cohorts based on type of operation: SC or cranial vault remolding. The Kid inpatient Database (KiD) database was used to assess sociodemographic factors in relation to craniosynostosis. Univariate and multivariate logistic regression were used to determine significant predictors and differences.

Results:

Single Institution (Regional): Compared with nonHispanic white (NHW) patients, Hispanic (OR 0.11), and NonHispanic Black (NHB) (OR 0.14) had lower odds of undergoing SC. Compared to those on private insurance, patients on Medicaid (OR 0.36) had lower odds of undergoing SC. Using zip code median income levels, patients with a higher median income level had slightly higher odds of undergoing SC compared to patients with a lower median income (OR 1.000025).

KIDS (National):

Compared with non-Hispanic white patients, NHB (OR 0.32) and Asian (OR 0.47) patients had lower odds of undergoing repair before the age of 1. Compared to patients with private insurance, those with Medicaid (OR 0.67) and self-pay (OR 0.58) had lower odds of undergoing repair before the age of 1. Patients in the lowest income quartile (OR 0.68) and second lowest income quartile (OR 0.71) had lower odds of undergoing repair before the age of 1 compared to the highest quartile.

Conclusions:

Our findings indicate that sociodemographic and socioeconomic factors may play a role in diagnosis of craniosynostosis and access to care. Patients of NHB and Hispanic race, lower income quartiles by zip code, and those that use public insurance are less likely to undergo early repair, both nationally and at our institution. Further research is needed to delineate the casualty of this disparity in presentation and timing of surgery.
Chemical biology-whole genome engineering datasets predict new antibacterial combinations
Authors: Turner Arthur K. , Yasir Muhammad , Bastkowski Sarah , Telatin Andrea , Page Andrew , Webber Mark , Charles Ian
Published: December 2021

Trimethoprim and sulfamethoxazole are used commonly together as cotrimoxazole for the treatment of urinary tract and other infections. The evolution of resistance to these and other antibacterials threatens therapeutic options for clinicians. We generated and analysed a chemical-biology-whole-genome data set to predict new targets for antibacterial combinations with trimethoprim and sulfamethoxazole. For this we used a large transposon mutant library in

Escherichia coli

BW25113 where an outward-transcribing inducible promoter was engineered into one end of the transposon. This approach allows regulated expression of adjacent genes in addition to gene inactivation at transposon insertion sites, a methodology that has been called TraDIS-Xpress. These chemical genomic data sets identified mechanisms for both reduced and increased susceptibility to trimethoprim and sulfamethoxazole. The data identified that over-expression of FolA reduced trimethoprim susceptibility, a known mechanism for reduced susceptibility. In addition, transposon insertions into the genes tdk, deoR, ybbC, hha, ldcA, wbbK and waaS increased susceptibility to trimethoprim and likewise for rsmH, fadR, ddlB, nlpI and prc with sulfamethoxazole, while insertions in ispD, uspC, minC, minD, yebK, truD and umpG increased susceptibility to both these antibiotics. Two of these genes’ products, Tdk and IspD, are inhibited by AZT and fosmidomycin respectively, antibiotics that are known to synergise with trimethoprim. Thus, the data identified two known targets and several new target candidates for the development of co-drugs that synergise with trimethoprim, sulfamethoxazole or cotrimoxazole. We demonstrate that the TraDIS-Xpress technology can be used to generate information-rich chemical-genomic data sets that can be used for antibacterial development.
Predictions of the SARS-CoV-2 Omicron Variant (B.1.1.529) Spike Protein Receptor-Binding Domain Structure and Neutralizing Antibody Interactions
Authors: Ford Colby T. , Machado Denis Jacob , Janies Daniel A.
Published: December 2021

The genome of the SARS-CoV-2 Omicron variant (B.1.1.529) was released on November 22, 2021, which has caused a flurry of media attention due the large number of mutations it contains. These raw data have spurred questions around vaccine efficacy. Given that neither the structural information nor the experimentally-derived antibody interaction of this variant are available, we have turned to predictive computational methods to model the mutated structure of the spike protein’s receptor binding domain and posit potential changes to vaccine efficacy. In this study, we predict some structural changes in the receptor-binding domain that may reduce antibody interaction without completely evading existing neutralizing antibodies (and therefore current vaccines).
Characteristics and data reporting of rare disease clinical trials: Getting better but still room for improvement
Authors: Mair Nina K. , Gottowik Jürgen , Rodriguez-Esteban Raul , Seabrook Timothy J.
Published: December 2021

Background

It is estimated that there are more than 7,000 rare diseases (RDs) worldwide, impacting the lives of approximately 400 million people and only 5% have an approved therapy. Facing special challenges, including patient scarceness, incomplete knowledge of the natural history and only few specialized clinical sites, clinical trials (CT) are limited, making the data from trials critical for research and clinical care. Despite the introduction of the U.S. Food and Drug Administration Amendment Act (FDAAA) in 2007 requiring certain CTs to post results on the registry ClinicalTrials.gov within 12 months following completion, compliance has been reportedly poor. Here, we describe general characteristics of RD CTs, identify trends, and evaluate result reporting practices under the FDAAA aiming to draw awareness to the problem of non-compliance.

Methods

CTs conducted between 2008 and 2015 were extracted from the public U.S. trial registry ClinicalTrials.gov using the text mining software I2E (Linguamatics). Disease names were matched with rare disease names from the Orphanet Rare Disease Ontology (ORDO, v2.5, Orphanet). Statistical analyses and data visualization were performed using GraphPad Prism 7 and R (v3.5). The Student’s t-test was employed to calculate significance using p-value cut-offs of <0.05 or <0.001.

Results

We analyzed 1,056 RD CTs of which 55.7% were phase 2, 7.7% phase 2/3 and 36.7% phase 3 trials. The studies were mostly one- and two-armed experimental CTs with the majority (60.2%) being funded by industry. Cystic fibrosis and sickle cell disease represented the most frequently investigated diseases (25.0% and 16.5%). Industry-led phase 2 RD CTs were significantly (p<0.0001) shorter than their equivalent led by academia/non-profit (22 vs. 33 months). Screening CTs completed before the end of 2015, we found that of the 725 analyzed studies, 55.2% predominantly phase 2 CTs, did not report results. Taking their potential applicability to the FDAAA into account, 25.2% industry-funded and 28.0% academia/non-profit-funded trials failed to disclose results on ClinicalTrial.gov.

Conclusion

RD CTs tend to be comparatively small, industry-funded studies focusing on genetic and neurologic conditions. Sponsor-related differences in study design, duration, and enrollment were observed. There are still substantial shortcomings when it comes to result publication.