bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating Causal Effects of Particulate Matter Regulation on Mortality
Authors: Sanders Nicholas J. , Barreca Alan I. , Neidell Matthew J.
Published: December 2019

Background:

Estimating the causal effect of pollution on human health is integral for evaluating returns to pollution regulation, yet separating out confounding factors remains a perennial challenge.

Methods:

We use a quasi-experimental design to investigate the causal relationship between regulation of particulate matter smaller than 2.5 micrograms per cubic meter (PM2.5) and mortality among those 65 years of age and older. We exploit regulatory changes in the Clean Air Act Amendments (CAAA). Regulation in 2005 impacted areas of the United States differentially based on pre-regulation air quality levels for PM2.5. We use county-level mortality data, extracted from claims data managed by the Centers for Medicare & Medicaid Services, merged to county-level average PM2.5 readings and attainment status as classified by the Environmental Protection Agency.

Results:

Based on estimates from log-linear difference-in-differences models, our results indicate after the CAAA designation for PM2.5 in 2005, PM2.5 levels decreased 1.59 micrograms per cubic meter (95% CI = 1.39, 1.80) and mortality rates among those 65 and older decreased by 0.93% (95% CI = 0.10%, 1.77%) in nonattainment counties, relative to attainment ones. Results are robust to a series of alternate models, including nearest-neighbor matching based on propensity score estimates.

Conclusion:

This analysis suggests large health returns to the 2005 PM2.5 designations, and provides evidence of a causal association between pollution and mortality among the Medicare population.
Split-skin Paddle Anterolateral Thigh Flap for Reconstruction of Giant Dermatofibrosarcoma Protuberans in Groin
Authors: Fukuta Taro , Ichikawa Yuichi , Mizuno Hiroshi , Hayashi Ayato
Published: December 2019

Dermatofibrosarcoma protuberans (DFSP) is a slow-growing superficial sarcoma. Due to its high late local recurrence, thin skin graft is usually recommended for reconstruction after resection of the tumor. In this report, we present a case of giant DFSP in the groin region of young woman. Reconstruction of large groin defect after DFSP resection was performed by “split-skin paddle anterolateral thigh flap” instead of skin graft considering that the patient was a 29-year-old woman. This method enabled the primary closure of the donor site and provided the positive functional and esthetic outcomes. In the present case, the surgical scar is less conspicuous and the patient can climb and descend stairs without any trouble at 4 years after the surgery. With careful monitoring of the tumor recurrence, this technique may become a reliable reconstruction option for patients with large groin defect after resection of the malignant tumor.
A Nanofiber Sheet Incorporating Vitamin B12 Promotes Nerve Regeneration in a Rat Neurorrhaphy Model
Authors: Miyamura Satoshi , Iwahashi Toru , Sayanagi Junichi , Hirai Yukio , Okada Kiyoshi , Oka Kunihiro , Niiyama Eri , Uto Koichiro , Ebara Mitsuhiro , Yoshikawa Hideki , Murase Tsuyoshi , Tanaka Hiroyuki
Published: December 2019

Background:

Outcomes of peripheral nerve repair after injury are often suboptimal. Therefore, developing biological approaches to augment nerve regeneration is important. In this in vivo study, we tested the hypothesis that augmentation with an electrospun nanofiber sheet incorporating methylcobalamin (MeCbl) would be effective for regeneration after peripheral nerve transection and repair.

Methods:

Rats were divided into 3 groups that either underwent sciatic nerve repair with or without the MeCbl sheet, or a sham operation. At 4 and/or 8 weeks after the operation, sensory and motor functional recovery, along with histological findings, were compared among the groups using the toe-spreading test, mechanical and thermal algesimetry tests, tibialis anterior muscle weight measurements, electrophysiological analyses, which included nerve conduction velocity (NCV), compound muscle action potential (CMAP), and terminal latency (TL), and histological analyses involving the myelinated axon ratio, axon diameter, and total axon number.

Results:

Compared with the repair group without the MeCbl sheet, the repair group with the MeCbl sheet showed significant recovery in terms of tibialis anterior muscle weight, NCV and CMAP, and also tended to improve in the toe-spreading test, mechanical and thermal algesimetry tests, and TL. Histological analyses also demonstrated that the myelinated axon ratios and axon diameters were significantly higher. Among these findings, the repair group with the MeCbl sheet demonstrated the same recovery in NCV as the sham group.

Conclusion:

This study demonstrated that electrospun nanofiber MeCbl sheets promoted nerve regeneration and functional recovery, indicating that this treatment strategy may be viable for human peripheral nerve injuries.
Mixed Tumor of the Nasal Root
Authors: Ebisudani Shogo , Inagawa Kiichi , Suzuki Yoshinori , Osugi Ikuko , Takasu Miori , Hara Naoki
Published: December 2019

We reported the case of a 53-year-old man who presented with over 25-year history of a soft tissue on the nasal root. The tumor with a diameter of 4 cm was observed on the nasal root, the mass was soft, freely mobile, and painless on palpation. No adhesion with the nasal bone was observed. Magnetic resonance imaging revealed multiple nodular solid tumor masses. There was a region with low contrast in the tumor, and adipose tissue was confirmed. We performed total excision. Histopathological examination revealed that the tumor had multiple nodular lesions, and epithelial component had glandular features and a myxoid stromal component. So, we diagnosed mixed tumor of the skin. To the best of our knowledge, it seems to be the largest in the mixed tumor of the skin that occurred in the nasal root in the previous reports.
Retinal arteriolar wall-to-lumen ratios at 16–17 years in the Copenhagen Child Cohort 2000 Study
Authors: Laigaard Poul P. , Larsen Michael , Hansen Mathias H. , Jeppesen Jørgen , Olsen Else Marie , Skovgaard Anne Mette , Munch Inger C.
Published: December 2019

Purpose:

To study the thickness of retinal arteriolar walls in a population-based cohort of adolescents.

Methods:

This cross-sectional, observational study included 1217 participants aged 16–17 years from the Copenhagen Child Cohort 2000 Study. The wall thickness and lumen diameter of a major branch retinal arteriole were measured using adaptive optics imaging. The wall-to-lumen ratio was analyzed in relation to blood pressure and body composition variables using a general linear model. Overall in the study population, wall-to-lumen ratio was found to decrease by 0.49% per μm increase in arteriole diameter (P < 0.0001) and all subsequent analyzes were adjusted accordingly.

Results:

The average outer and inner arteriole diameters were 117 ± 19 and 96.6 ± 18 μm (mean ± SD), corresponding to a wall-to-lumen ratio of 0.21 ± 0.024. There was no detectable difference between sexes. A higher wall-to-lumen ratio was associated with a higher BMI (+0.21% per kg/m2, P = 0.0018), higher body fat percentage (+0.097% per 1% increase, P = 0.0052), wider hip circumference (+1.1% per 10 cm increase, P = 0.0006), wider waist circumference (+0.92% per 10 cm increase, P = 0.0009), higher SBP in girls (+1.1% per 10 mmHg increase, P = 0.0005), longer axial length (+0.70% per mm increase, P = 0.013), and younger age (+4.9% per year younger, P < 0.0001), adjusted for arteriole diameter, age, sex, and height.

Conclusion:

A higher retinal arteriolar wall-to-lumen ratio was associated with all registered indices of body fat proportion.
Registry of Plutonium-induced Lung Fibrosis in a Russian Nuclear Worker Cohort
Authors: Azizova Tamara , Moseeva Maria , Grigoryeva Evgeniya , Zhuntova Galina , Bannikova Maria , Sychugov Gleb , Kazachkov Evgeny
Published: December 2019

A registry of plutonium-induced lung fibrosis diagnosed in members of a cohort of the first Russian nuclear industry facility Mayak Production Association was established. The registry includes 188 plutonium-induced lung fibrosis diagnoses: 117 (62.23%) in males and 71 (37.77%) in females. This paper describes the structure and detailed characteristics of the registry. Plutonium-induced lung fibrosis was shown to have no association with cumulative lung absorbed dose from external gamma rays as of the date of diagnosis. On the contrary, the plutonium-induced lung fibrosis rate was shown to be associated with cumulative lung absorbed dose from incorporated alpha particles and to increase significantly with increasing dose from internal radiation exposure. This paper discusses potential applications of the registry to scientific investigations in the future.
A Review on Evidence-Based Treatments for Meibomian Gland Dysfunction
Authors: Lam Pun Yuet , Shih Kendrick Co , Fong Pak Yui , Chan Tommy Chung Yan , Ng Alex Lap-Ki , Jhanji Vishal , Tong Louis
Published: December 2019

Objectives:

To evaluate recent studies on available therapies for meibomian gland dysfunction (MGD).

Methods:

A literature search on recent publications, within the last five years, concerning treatment options for MGD was performed.

Results:

A total of 35 articles were reviewed after curation by the authors for relevance. In general, all modalities of treatments were shown to have clinical efficacy in alleviating dry eye signs and symptoms, although the extent of improvement and persistency of outcomes varied between the different treatments. Evidence from published studies demonstrate that thermal pulsation produces the longest lasting effect per treatment, but it also incurs the highest per-treatment cost. Reusable methods for warm compress with lipid/semi-fluorinated alkane-containing eye drops are recommended as first-line treatment for mild-to-moderate dry eye patients, because this option is most technically feasible and cost-effective in clinical practice. Intense pulsed light (IPL) therapy and thermal pulsation may be suitable as second line for patients unresponsive to warm compress therapy; however, their respective limitations need to be considered. For refractory MGD with features of periductal fibrosis or severe blepharitis, supplementary treatment with meibomian gland probing or oral antibiotics may be used.

Conclusions:

All eight forms of treatments, including self-applied eyelid warming, thermal pulsation, IPL, MG probing, antibiotics, lipid-containing eye drops, and perfluorohexyloctane, were effective against MGD, although with varying extent of clinical improvements. A better understanding on the mechanisms of actions may guide physicians to make better treatment decisions targeting the root causes.
Detangling red hair from pain: phenotype-specific contributions from different genetic variants in melanocortin-1 receptor
Authors: Zorina-Lichtenwalter Katerina , Maixner William , Diatchenko Luda
Published: December 2019

Genetic variation in melanocortin-1 receptor (MC1R) has a known role in red hair. Studies on responses to noxious stimuli in red-haired individuals have also been conducted, with mixed findings. To investigate a possible divergence between variants responsible for red hair and pain sensitivity, we performed a genewide association analysis in the Orofacial Pain: Prospective Evaluation and Risk Assessment cohort. All genotyped (17) MC1R variants were tested for association with heat pain temporal summation and sensitivity. Our analyses showed an association for pain sensitivity with the 5′-UTR, tagged by rs3212361, and 1 missense variant, rs885479 (R163Q), previously shown to be weakly associated with red hair. For both variants, the minor allele was protective. These results were validated in the 500,000-person UK Biobank cohort, where the minor alleles of rs3212361 and rs885479 were associated with a reduced count of persistent pain conditions as well as individual pain conditions. Haplotype association analysis revealed a possible joint effect from the 2 individual variants. The 5′-UTR variant rs3212361 was further identified as an expression quantitative trait locus, associated with reduced transcript levels of MC1R in the brain and in the peripheral tibial nerve. Hair colour association analysis of the loss-of-function 5′-UTR rs3212361 allele identified association with red hair, and red hair colour itself was associated with a reduced count of persistent pain conditions. Together, our results suggest that primarily different mechanisms—affecting expression levels vs protein activity—mediated by different genetic variants in the MC1R locus contribute to red hair and pain.
An Approach to Hazardous Medication Surveillance
Authors: Breeher Laura E. , Stonelake-French Heather L.
Published: December 2019

Many health care organizations are making changes to their hazardous medication surveillance program (HMSP) in response to United States Pharmacopeia (USP) <800> standards. Absence of best practices for HMSPs and limitations on the ability of such programs to correlate health effects identified on surveillance with workplace exposures historically have left health care institutions to determine if and how to design an HMSP for their workforce. Within this article one approach to the design of an HMSP is discussed and resources such as a health questionnaire and declination form are included that could be modified or adopted by other health care organizations. This information is intended to generate further discussion and collaboration among leaders of employee occupational health services on a national level to address the benefits and challenges of HMSPs.
Small Business Employees’ Perceptions of Leadership Are Associated With Safety and Health Climates and Their Own Behaviors
Authors: Shore Erin , Schwatka Natalie , Dally Miranda , Brown Carol E. , Tenney Liliana , Newman Lee S.
Published: December 2019

Objective:

Leadership is an important factor in creating a safe and healthy work environment. Little is known about its influence in small organizations. This study assessed the relationship between leadership, climate, and employee behavior in organizations with less than 500 employees.

Methods:

We examined organizational factors and worker perceptions of leadership and safety/health behaviors in an analysis of 1271 employees in 53 Colorado small organizations. Cross-sectional relationships were assessed using multivariable linear regression models.

Results:

Perceived leadership commitment to safety was associated with safety climate (β = 0.67) and safety behaviors among employees (β = 0.45). Perceived leadership commitment to worksite wellness was associated with health climate (β = 0.66) and health behaviors (β = 0.42).

Conclusions:

Leadership plays an important role in creating a positive work environment around safety and health.
Comparison of prognostic significance between serum fibrinogen and Global Registry of Acute Coronary Events score for prognosis of patients with non-ST-elevation acute coronary syndromes undergoing percutaneous coronary intervention
Authors: Song Jia , Yu Tongtong , Sun Zhijun , Li Zhichao , He Dongxu , Sun Zhaoqing
Published: December 2019

Objective

An elevated fibrinogen level has been demonstrated to be a predictor of adverse coronary heart disease outcome. This study aimed to assess whether fibrinogen is a useful marker to predict the prognosis of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). Additionally, the prognostic accuracy of fibrinogen level was compared with that of the Global Registry of Acute Coronary Events (GRACE) score.

Methods

A total of 1211 patients with NSTE-ACS undergoing PCI were analyzed in a prospective cohort study. The enrolled patients were divided into a low fibrinogen group (n = 826, fibrinogen ≤ 3.49 mg/dl) and a high fibrinogen group (n = 385, fibrinogen > 3.49 mg/dl) based on a receiver operating characteristic (ROC) curve. The clinical endpoints were death and death/nonfatal reinfarction. An ROC curve analysis was performed and the area under the curve with a 95% confidence interval (CI) was derived and compared with those for the GRACE score to determine the diagnostic value of the serum fibrinogen level.

Results

Multivariate analysis showed that an elevated baseline fibrinogen level was an independent predictor of death/nonfatal reinfarction (hazard ratio = 1.498, 95% CI: 1.030–2.181, P = 0.035). The prognostic performance of fibrinogen was equivalent to that of the GRACE system in predicting clinical endpoints (C-statistic: z = 1.486, P = 0.14).

Conclusion

Fibrinogen is an independent predictor of death/nonfatal reinfarction in patients with NSTE-ACS undergoing PCI, and its accuracy is similar to that of the GRACE system.
Use of pinhole dual-phase Tc-99m sestamibi vs combined Tc-99m sestamibi and Tc-99m pertechnetate scintigraphy in patients with hyperparathyroidism where single-photon emission computed tomography/computed tomography is unavailable
Authors: Juweid Malik Eid , Omari Yanal , Khawaja Nahla , AlSharif Abedallatif , Al-Monyer Suhad , Jwaied Sara , Shaban Liza , Laham Cathrina , Alajlony Eyad , Karkash Ahmad , Ajlouni Kamel
Published: December 2019

Objective

To compare the sensitivity and positive predictive value (PPV) of pinhole dual-phase Tc-99m sestamibi vs combined Tc-99m sestamibi and Tc-99m pertechnetate scintigraphy in patients with hyperparathyroidism where single-photon emission computed tomography (SPECT)/CT is unavailable.

Methods

All patients with biochemically proven hyperparathyroidism who underwent both pinhole Tc-99m sestamibi and Tc-99m pertechnetate scintigraphy between January 2012 and December 2017 with surgery performed within 3 months of imaging were analyzed. Tc-99m sestamibi images alone and combined with Tc-99m pertechnetate images were interpreted by two nuclear medicine physicians. The sensitivity and PPV of the two imaging approaches were determined based on the surgical findings.

Results

Of the 38 patients included, surgery revealed 33 single parathyroid adenomas (PA), one double adenoma and four parathyroid hyperplasia (PH). On a per-patient basis, the sensitivity and PPV for detection of PA or PH were 76% and 100%, respectively, with Tc-99m sestamibi alone vs 84% and 100% using the combined approach. For PA, the sensitivity and PPV were 82% and 100%, respectively, with Tc-99m sestamibi alone vs. 91% and 100% with the combined approach. PH was identified in only one of four patients with Tc-99m sestamibi alone or in combination. There were no significant differences in sensitivity (P = 0.08) and PPV (P > 0.99) between Tc-99m sestamibi alone and Tc-99m sestamibi with Tc-99m pertechnetate.

Conclusion

Pinhole dual-phase Tc-99m sestamibi alone has high accuracy in the detection of PA. The routine addition of Tc-99m pertechnetate to Tc-99m sestamibi does not result in significant improvement in the detection of PA or PH and should be reserved for equivocal cases.
Stem-cell therapy for bronchopulmonary dysplasia
Authors: Collins Amélie
Published: December 2019

Purpose of review

Clinical trials of mesenchymal stem/stromal cell (MSC) therapy for bronchopulmonary dysplasia (BPD) are underway. A thorough understanding of the preclinical work that underpins these trials is critical for neonatal practitioners to properly evaluate them.

Recent findings

Significant progress has been made in understanding that MSCs have anti-inflammatory and proangiogenic effects, and that these can be mediated by the noncellular exosome fraction of MSCs.

In rodent hyperoxia models of BPD, MSCs have a proangiogenic effect mediated largely by vascular endothelial growth factor and shift the balance of endogenous lung cells from a proinflammatory to a prohealing phenotype. MSC-derived exosomes can recapitulate these effects.
Kidney stones and the opioid epidemic: recent developments and review of the literature
Authors: Krughoff Kevin , Pais Vernon M.
Published: December 2019

Purpose of review

A public health emergency has been declared in response to rising opioid addiction and opioid-related deaths in the United States. As kidney stones have been identified as an important source of initial and repeated opioid exposures, this review seeks to describe the scope of the problem and report relevant alternatives to opioid analgesia for stones.

Recent findings

Recent literature summarizing the extent of opioid use among those with stones is reviewed. A number of opioid-minimizing strategies and analgesic regimens have been proposed and studied. A review of these modifications and alternatives is provided.

Both symptomatic renal colic and surgical interventions to address stones may prompt need for analgesia. Reducing prescribed opioids reduces both patient use and risk of diversion. Modifications in surgical technique, administration of local anesthetics, and use of systemic nonopioid analgesics have all been successfully employed.
Transcutaneous Carbon Dioxide Monitoring During Apnea Testing for Determination of Neurologic Death in Children: A Retrospective Case Series*
Authors: Sochet Anthony A. , Bingham Ladonna , Sreedhar Sue , Teppa Beatriz , Vose Laura A. , Nakagawa Thomas A.
Published: December 2019

Objectives:

Determination of neurologic death in children is a clinical diagnosis based on absence of neurologic function with irreversible coma and apnea. Apnea testing during determination of neurologic death assesses spontaneous respiration when Paco2increases to greater than or equal to 60 and greater than or equal to 20 mm Hg above pre-apneic baseline. The utility of transcutaneous carbon dioxide measurements during apnea testing in children is unknown. We seek to determine the degree of correlation between paired transcutaneous carbon dioxide and Paco2values during apnea testing for determination of neurologic death.

Design:

Single-center, retrospective case series.

Setting:

Twenty-eight bed PICU in a 259-bed, tertiary care, referral center.

Patients:

Children 0–18 years old undergoing determination of neurologic death between May 2017 and December 2018.

Interventions:

None.

Measurements and Main Results:

Primary outcomes were paired transcutaneous carbon dioxide and Paco2values obtained during determination of neurologic death. Primary analyses included Pearson correlation coefficient, Bland-Altman bias and limits of agreement, and comparative statistics. Descriptive data included demographics, admission diagnoses, hemodynamics, Vasoactive Inotropic Scores, and arterial blood gas measurement. Eight children underwent 15 determination of neurologic death examinations resulting in 31 paired transcutaneous carbon dioxide and Paco2values for study. Transcutaneous carbon dioxide and Paco2correlated well (r= 0.94;p< 0.01). Bias between transcutaneous carbon dioxide and Paco2was –3.29 ± 7.14 mm Hg. Differences in means did not correlate with Vasoactive Inotropic Score (r= 0.2) or patient temperature (r= 0.11). Receiver operator characteristic curve of transcutaneous carbon dioxide after 3–10 minutes of apnea to discriminate positive apnea testing by the standard of Paco2yielded an area under the curve of 0.91 and threshold of greater than or equal to 64 mm Hg (sensitivity, 91.7%; specificity, 100%; positive predictive value, 100%; negative predictive value, 92.3%; accuracy, 95.9%).

Conclusions:

During apnea testing for determination of neurologic death in children, noninvasive transcutaneous carbon dioxide monitoring demonstrated high correlation, accuracy, and minimal bias when compared with Paco2. Further validation is required before any recommendation to replace Paco2with noninvasive transcutaneous carbon dioxide monitoring can be proposed. However, concurrent transcutaneous carbon dioxide data may limit unnecessary apnea time and associated hemodynamic instability or respiratory decompensation by approximating goal arterial blood sampling to document target Paco2.
Ultrasonography in Distal Ulnar Nerve Neuropathy: Findings in 33 Patients
Authors: Iyer Vasudeva G.
Published: December 2019

Purpose:

Although there are many case reports on the role of ultrasonography (US) in distal ulnar nerve neuropathy (Guyon canal syndrome), there is a paucity of large series in the literature because of its rarity. During an 8-year period, 33 instances of electrodiagnostically confirmed cases underwent US imaging. These cases were analyzed to determine the role of US in uncovering the cause of distal ulnar nerve neuropathy and its contribution to further management.

Methods:

This was a retrospective study of patients diagnosed with distal ulnar nerve neuropathy based on electrodiagnostic criteria, who also had undergone US (measurement of the cross-sectional area and documentation of causes such as cysts and neuromas).

Results:

US showed normal ulnar nerve in 5, cysts in 10, neuromas in 2, and nonspecific enlargement in 16 patients. Surgery was performed in 15 patients, and the US findings were corroborated in those with cysts and neuromas; 1 patient had an aberrant muscle, and two had fibrous bands constricting the ulnar nerve in the Guyon canal (not detected preoperatively by US imaging).

Conclusions:

US imaging detected the underlying cause of distal ulnar nerve neuropathy in a significant percentage of patients, potentially contributing to effective treatment.
Scalp EEG Could Record Both Ictal Direct Current Shift and High-Frequency Oscillation Together Even With a Time Constant of 2 Seconds
Authors: Murai Tomohiko , Hitomi Takefumi , Matsuhashi Masao , Matsumoto Riki , Kawamura Yuki , Kanda Masutaro , Takahashi Ryosuke , Ikeda Akio
Published: December 2019

Herein, the authors report for the first time, scalp-recorded (1) focal ictal direct current (DC) shifts (active DC shifts; that precede conventional pattern) from the chronic focus of focal epilepsy and (2) ictal high-frequency oscillation after ictal DC shifts (passive DC shifts; that follow both conventional and high-frequency oscillation ictal patterns) from the acute focus of acute symptomatic seizures (Szs) in a 77-year-old man. Sixteen episodes of clinical Szs were recorded by scalp EEG with a 2-seconds time constant. Among the 16 recorded episodes of Sz, four EEG Sz patterns originated from the left posterior temporal area (chronic focus), and all patterns (100%) exhibited active DC shifts preceding the conventional pattern by 12 seconds. Twelve EEG Sz patterns originated from the right parietal area (acute focus), and the high-frequency oscillations (five Szs) (41.6%) and DC shifts (six Szs) (50%) occurred first, followed by the conventional pattern 8 seconds later. Because both the active and the passive DC shifts were recorded with a time constant of 2 seconds, which was smaller than that reported previously for ictal DC shifts (e.g., time constant of 10 seconds), clinically useful ictal DC shifts could be routinely inspected with a time constant of 2 seconds.
Self-determination in adolescents and adults with intellectual and developmental disabilities
Authors: Wehmeyer Michael L.
Published: December 2019

Purpose of review

The importance of self-determination to wellbeing and life satisfaction has been established by research in motivation and education. The present review provides a synthesis of research in these areas at a time when the two lines of research are converging.

Recent findings

Research has established that youth and adults with intellectual and developmental disabilities (IDD) are not as self-determined as their nondisabled peers and that this negatively impacts the quality of their lives. Further, research has established the positive benefits of a focus on self-determination assessment and intervention for people with IDD. Recent studies illustrate the shifting focus to a life-course development perspective of self-determination and the alignment of assessment and interventions with that perspective. Research on self-determination and IDD outside of the United States has dramatically increased.

Research shows that people with IDD who are more self-determined achieve more positive school and adult outcomes and higher life satisfaction. Assessment of and interventions to promote self-determination have increasingly emphasized all people and are aligning with research in motivation and positive psychology. This provides a foundation for promoting greater community, school, and work inclusion.
Public health impact of foodborne exposure to naturally occurring virulence-attenuatedListeria monocytogenes:inference from mouse and mathematical models
Authors: Stout Alison , Van Stelten-Carlson Anna , Marquis Hélène , Ballou Michael , Reilly Brian , Loneragan Guy H. , Nightingale Kendra , Ivanek Renata
Published: December 2019

Listeriosis is a clinically severe foodborne disease caused byListeria monocytogenes(Lm). However, approximately 45% of Lm isolates in food carry a virulence-attenuating single-nucleotide polymorphism ininlA, which normally facilitates crossing the intestinal barrier during the initial stages of infection. We hypothesized that (i) natural exposure to virulence-attenuated (vA) Lm strains through food can confer protective immunity against listeriosis attributable to fully virulent (fV) strains and (ii) current food safety measures to minimize exposure to both Lm strains may have adverse population-level outcomes. To test these hypotheses, we evaluated the host response to Lm in a mouse infection model and through mathematical modelling in a human population. After oral immunization with a murinized vA Lm strain, we demonstrated the elicitation of a CD8+ T-cell response and protection against subsequent challenge with an fV strain. A two-strain compartmental mathematical model of human exposure to Lm with cross-protective immunity was also developed. If food safety testing strategies preferentially identify and remove food contaminated by vA strains (potentially due to their common occurrence in foods and higher concentration in food compared to fV strains), the model predicted minimal public health benefit to potentially adverse effects. For example, reducing vA exposures by half, while maintaining fV exposures results in an approximately 6% rise in annual incidence.
A general method for multiscale modelling of vector-borne disease systems
Authors: Garira Winston , Chirove Faraimunashe
Published: December 2019

The inability to develop multiscale models which can describe vector-borne disease systems in terms of the complete pathogen life cycle which represents multiple targets for control has hindered progress in our efforts to control, eliminate and even eradicate these multi-host infections. This is because it is currently not easy to determine precisely where and how in the life cycles of vector-borne disease systems the key constrains which are regarded as crucial in regulating pathogen population dynamics in both the vertebrate host and vector host operate. In this article, we present a general method for development of multiscale models of vector-borne disease systems which integrate the within-host and between-host scales for the two hosts (a vertebrate host and a vector host) that are implicated in vector-borne disease dynamics. The general multiscale modelling method is an extension of our previous work on multiscale models of infectious disease systems which established a basic science and accompanying theory of how pathogen population dynamics at within-host scale scales up to between-host scale and in turn how it scales down from between-host scale to within-host scale. Further, the general method is applied to multiscale modelling of human onchocerciasis—a vector-borne disease system which is sometimes called river blindness as a case study.
Reverse engineering gene networks using global–local shrinkage rules
Authors: Panchal Viral , Linder Daniel F.
Published: December 2019

Inferring gene regulatory networks from high-throughput ‘omics’ data has proven to be a computationally demanding task of critical importance. Frequently, the classical methods break down owing to the curse of dimensionality, and popular strategies to overcome this are typically based on regularized versions of the classical methods. However, these approaches rely on loss functions that may not be robust and usually do not allow for the incorporation of prior information in a straightforward way. Fully Bayesian methods are equipped to handle both of these shortcomings quite naturally, and they offer the potential for improvements in network structure learning. We propose a Bayesian hierarchical model to reconstruct gene regulatory networks from time-series gene expression data, such as those common in perturbation experiments of biological systems. The proposed methodology uses global–local shrinkage priors for posterior selection of regulatory edges and relaxes the common normal likelihood assumption in order to allow for heavy-tailed data, which were shown in several of the cited references to severely impact network inference. We provide a sufficient condition for posterior propriety and derive an efficient Markov chain Monte Carlo via Gibbs sampling in the electronic supplementary material. We describe a novel way to detect multiple scales based on the corresponding posterior quantities. Finally, we demonstrate the performance of our approach in a simulation study and compare it with existing methods on real data from a T-cell activation study.
On modelling environmentally transmitted pathogens
Authors: Lanzas Cristina , Davies Kale , Erwin Samantha , Dawson Daniel
Published: December 2019

Many pathogens are able to replicate or survive in abiotic environments. Disease transmission models that include environmental reservoirs and environment-to-host transmission have used a variety of functional forms and modelling frameworks without a clear connection to pathogen ecology or space and time scales. We present a conceptual framework to organize microparasites based on the role that abiotic environments play in their lifecycle. Mean-field and individual-based models for environmental transmission are analysed and compared. We show considerable divergence between both modelling approaches when conditions do not facilitate well mixing and for pathogens with fast dynamics in the environment. We conclude with recommendations for modelling environmentally transmitted pathogens based on the pathogen lifecycle and time and spatial scales of the host–pathogen system under consideration.
Estimating viral bottleneck sizes for FMDV transmission within and between hosts and implications for the rate of viral evolution
Authors: Orton Richard J. , Wright Caroline F. , King Donald P. , Haydon Daniel T.
Published: December 2019

RNA viruses exist as populations of closely related genomes, characterized by a high diversity of low-frequency variants. As viral genomes from one population disperse to establish new sites of replication, the fate of these low-frequency variants depends to a large extent on the size of the founding population. Focusing on foot-and-mouth disease virus (FMDV) we conjecture that variants are more likely to be transmitted through wide bottlenecks, but more likely to approach fixation in new populations following narrow bottlenecks; therefore, the longer-term rate of accumulation of ‘nearly neutral’ variants at high frequencies is likely to be inversely related to the bottleneck size. We examine this conjecturein vivoby estimating bottleneck sizes relating ‘parent’ and ‘daughter’ populations observed at different scales ranging from within host to between host (within the same herd, and in different herds) using a previously established method. Within hosts, we find bottleneck sizes to range from 5 to 20 viral genomes between populations transmitted from the pharynx to the serum, and from 4 to 54 between serum and lesion populations. Between hosts, we find bottleneck sizes to range from 2 to 39, suggesting inter-host bottlenecks are of a similar size to intra-host bottlenecks. We establish a statistically significant negative relationship between the probability of genomic consensus level change and bottleneck size, and present a simple sampling model that captures this empirical relationship. We also present a novelin vitroexperiment to investigate the impact of bottleneck size on the frequency of mutations within FMDV populations, demonstrate that variant frequency in a population increases more rapidly during small population passages, and provide evidence for positive selection during the passage of large populations.
Nioella ostreopsis sp. nov., isolated from toxic dinoflagellate, Ostreopsis lenticularis
Authors: Yang Qiao , Jiang Zhiwei , Zhou Xin , Zhang Ruonan , Wu Yiru , Lou Linghao , Ma Zetao , Wang Dongfang , Ge Yaming , Zhang Xiaoling , Yu Xinwei
Published: December 2019

A novel short-rod-shaped bacterial strain with poly-β-hydroxybutyric acid granules inside, designated as Z7-4T, was isolated from a culture of a marine dinoflagellate with palytoxin-producing capacity, Ostreopsis lenticularis OS06, collected from the East China Sea. Cells of Z7-4T were Gram-stain-negative, non-motile, strictly aerobic, 0.9–1.2 µm wide and 2.0–3.9 µm long. Growth occurred in 1–4 % (w/v) NaCl, at 15–37 °C and at pH 5.0–10.0, with optimum growth in 3.5 % (w/v) NaCl, at 30 °C and at pH 7.0. Analysis of 16S rRNA gene sequence revealed that Z7-4T shared the highest 16S rRNA gene sequence similarities with

Nioella aestuarii

JCM 30752T (98.8 %), followed by

Nioella sediminis

KCTC 42144T (98.6 %) and

Nioella nitratireducens

KCTC 32417T (96.9 %). Phylogenetic analysis based on nearly complete 16S rRNA gene sequences revealed that Z7-4T clearly represented a member of the genus

Nioella

within the family

Rhodobacteraceae

. The respiratory quinone of Z7-4T was identified as Q-10. Polar lipids of Z7-4T were phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, three unidentified aminophospholipids and one unidentified phospholipid. The major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0. The DNA G+C content of Z7-4T was 63.0 mol%. DNA–DNA hybridization values of the isolate against the closely related type strains were far below the 70 % limit for species delineation. The average nucleotide identity and in silico DNA–DNA genome hybridization relatedness between Z7-4T and the closely related members of the genus

Nioella

,

N. sediminis

KCTC 42144T and

N. nitratireducens

KCTC 32417T, were 91.1 and 46.3 %, and 79.3 and 19.4 %, respectively. On the basis of the results of polyphasic analysis, Z7-4T is proposed to represent a novel species of the genus

Nioella

, for which the name Nioella ostreopsis sp. nov. is proposed. The type strain of Nioella ostreopsis is Z7-4T (=KCTC 62459T=CCTCC AB 2017231T)
Delving Below the Species Level To Characterize the Ecological Diversity within the Global Virome: An Exploration of West Nile Virus
Authors: Kong Tong , Mei Kelly , Wang Ammie , Krizanc Danny , Cohan Frederick M.
Published: December 2019

Efforts to describe the diversity of viruses have largely focused on classifying viruses at the species level. However, substantial ecological diversity, both in virulence level and host range, is known within virus species. Here we demonstrate a proof of concept for easily discovering ecological diversity within a virus species taxon. We have focused on the West Nile Virus to take advantage of its broad host range in nature. We produced a genome-based phylogeny of world diversity of WNV and then used Ecotype Simulation 2 to hypothesize demarcation of genomes into 69 putative ecotypes (ecologically distinct populations), based only on clustering of genome sequences. Then we looked for evidence of ecological divergence among ecotypes based on differences in host bird associations within the Connecticut-New York region. Our results indicated significant heterogeneity among ecotypes for their associations with different bird hosts. Ecological diversity within other zoonotic viruses could be easily discovered using this approach. Opportunities for extending this line of research to human associations of virus ecotypes are limited by missing geographic metadata on human samples.
Perceptual modulation of parietal activity during urgent saccadic choices
Authors: Seideman Joshua A. , Salinas Emilio , Stanford Terrence R.
Published: December 2019

The lateral intraparietal cortex (LIP) contributes to visuomotor transformations for determining where to look next. However, its spatial selectivity can signify attentional priority, motor planning, perceptual discrimination, or other mechanisms. Resolving how this LIP signal influences a perceptually guided choice requires knowing exactly when such signal arises and when the perceptual evaluation informs behavior. To achieve this, we recorded single-neuron activity while monkeys performed an urgent choice task for which the perceptual evaluation’s progress can be tracked millisecond by millisecond. The evoked presaccadic responses were strong, exhibited modest motor preference, and were only weakly modulated by sensory evidence. This modulation was remarkable, though, in that its time course preceded and paralleled that of behavioral performance (choice accuracy), and it closely resembled the statistical definition of confidence. The results indicate that, as the choice process unfolds, LIP dynamically combines attentional, motor, and perceptual signals, the former being much stronger than the latter.
Cleft lip and cleft palate (CL/P) inEsrp1KO mice is associated with alterations in Wnt signaling and epithelial-mesenchymal crosstalk
Authors: Lee SungKyoung , Sears Matthew J. , Zhang Zijun , Li Hong , Salhab Imad , Krebs Philippe , Xing Yi , Nah Hyun-Duck , Williams Trevor , Carstens Russ P.
Published: December 2019

Cleft lip is one of the most highly prevalent birth defects in human patients. However, there remain a limited number of mouse models of cleft lip and thus much work is needed to further characterize genes and mechanisms that lead to this disorder. It is well established that crosstalk between epithelial and mesenchymal cells underlies formation of the face and palate, yet the basic molecular events mediating this crosstalk are still poorly understood. We previously demonstrated that mice with ablation of the epithelial-specific splicing factor Esrp1 have fully penetrant bilateral CL/P. In this study we further investigated the mechanisms by which ablation of Esrp1 leads to cleft lip as well as cleft palate. These studies included a detailed analysis of the changes in splicing and total gene expression in embryonic ectoderm during formation of the face as well as gene expression changes in adjacent mesenchyme. We identified altered expression in components of pathways previously implicated in cleft lip and/or palate, including numerous components of the Wnt signaling pathway. These findings illustrate that maintenance of an Esrp1 regulated epithelial splicing program is essential for face development through regulation of key signaling pathways.
Genetic characterization ofStreptococcus equisubspecieszooepidemicusassociated with high swine mortality in United States
Authors: Chen Xuhua , Resende-De-Macedo Nubia , Sitthicharoenchai Panchan , Sahin Orhan , Burrough Eric , Clavijo Maria , Derscheid Rachel , Schwartz Kent , Lantz Kristina , Robbe-Austerman Suelee , Main Rodger , Li Ganwu
Published: December 2019

High mortality events due toStreptococcus equisubspecieszooepidemicus(S. zooepidemicus) in swine have not previously been reported in the United States. In September and October 2019, outbreaks with swine mortality up to 50% due toS. zooepidemicussepticemia were reported in Ohio and Tennessee. Genomic epidemiological analysis revealed that the eight outbreak isolates were clustered together with ATCC 36246, a Chinese strain caused outbreaks with high mortality, also closely related to three isolates from human cases from Virginia, but significantly different from an outbreak-unrelated swine isolate from Arizona and most isolates from other animal species. Comparative genomic analysis on two outbreak isolates and another outbreak-unrelated isolate identified several genomic islands and virulence genes specifically in the outbreak isolates only, which are likely associated with the high mortality observed in the swine population. These findings have implications for understanding, tracking, and possibly preventing diseases caused byS. zooepidemicusin swine.
Assembly of a young vertebrate Y chromosome reveals convergent signatures of sex chromosome evolution
Authors: Peichel Catherine L. , McCann Shaugnessy R. , Ross Joseph A. , Naftaly Alice F. S. , Urton James R. , Cech Jennifer N. , Grimwood Jane , Schmutz Jeremy , Myers Richard M. , Kingsley David M. , White Michael A.
Published: December 2019

Heteromorphic sex chromosomes have evolved repeatedly across diverse species. Suppression of recombination between X and Y chromosomes leads to rapid degeneration of the Y chromosome. However, these early stages of degeneration are not well understood, as complete Y chromosome sequence assemblies have only been generated across a handful of taxa with ancient sex chromosomes. Here we describe the assembly of the threespine stickleback (Gasterosteus aculeatus) Y chromosome, which is less than 26 million years old. Our previous work identified that the non-recombining region between the X and the Y spans ∼17.5 Mb on the X chromosome. Here, we combined long-read PacBio sequencing with a Hi-C-based proximity guided assembly to generate a 15.87 Mb assembly of the Y chromosome. Our assembly is concordant with cytogenetic maps and Sanger sequences of over 90 Y chromosome clones from a bacterial artificial chromosome (BAC) library. We found three evolutionary strata on the Y chromosome, consistent with the three inversions identified by our previous cytogenetic analyses. The young threespine stickleback Y shows convergence with older sex chromosomes in the retention of haploinsufficient genes and the accumulation of genes with testis-biased expression, many of which are recent duplicates. However, we found no evidence for large amplicons found in other sex chromosome systems. We also report an excellent candidate for the master sex-determination gene: a translocated copy ofAmh(Amhy). Together, our work shows that the same evolutionary forces shaping older sex chromosomes can cause remarkably rapid changes in the overall genetic architecture on young Y chromosomes.
Delicate balances in cancer chemotherapy: Modeling immune recruitment and emergence of systemic drug resistance
Authors: Tran Anh Phong , Al-Radhawi M. Ali , Kareva Irina , Wu Junjie , Waxman David J. , Sontag Eduardo D.
Published: December 2019

Metronomic chemotherapy can drastically enhance immunogenic tumor cell death. However, the responsible mechanisms are still incompletely understood. Here, we develop a mathematical model to elucidate the underlying complex interactions between tumor growth, immune system activation, and therapy-mediated immunogenic cell death. Our model is conceptually simple, yet it provides a surprisingly excellent fit to empirical data obtained from a GL261 mouse glioma model treated with cyclophosphamide on a metronomic schedule. The model includes terms representing immune recruitment as well as the emergence of drug resistance during prolonged metronomic treatments. Strikingly, a fixed set of parameters, not adjusted for individuals nor for drug schedule, excellently recapitulates experimental data across various drug regimens, including treatments administered at intervals ranging from 6 to 12 days. Additionally, the model predicts peak immune activation times, rediscovering experimental data that had not been used in parameter fitting or in model construction. The validated model was then used to make predictions about expected tumor-immune dynamics for novel drug administration schedules. Notably, the validated model suggests that immunostimulatory and immunosuppressive intermediates are responsible for the observed phenomena of resistance and immune cell recruitment, and thus for variation of responses with respect to different schedules of drug administration.