bluuebunny/crossref_metadata_2025 huggingface dataset:
A new approach to finding galaxy groups using Markov Clustering
Authors: Stothert L , Norberg P , Baugh C M
Published: March 2019

We present a proof of concept of a new galaxy group finder method, Markov graph CLustering (MCL) that naturally handles probabilistic linking criteria. We introduce a new figure of merit, the variation of information (VI) statistic, used to optimize the free parameter(s) of the MCL algorithm. We explain that the common friends-of-friends (FoF) method is a subset of MCL. We test MCL in real space on a realistic mock galaxy catalogue constructed from an N-body simulation using the galform model. With a fixed linking length FoF produces the best group catalogues as quantified by the VI statistic. By making the linking length sensitive to the local galaxy density, the quality of the FoF and MCL group catalogues improve significantly, with MCL being preferred over FoF due to a smaller VI value. The MCL group catalogue recovers accurately the underlying halo multiplicity function at all multiplicities. MCL provides better and more consistent group purity and halo completeness values at all multiplicities than FoF. As MCL allows for probabilistic pairwise connections, it is a promising algorithm to find galaxy groups in photometric surveys.
Reviewing the evidence on breast milk composition and immunological outcomes
Authors: Boix-Amorós Alba , Collado Maria Carmen , Van’t Land Belinda , Calvert Anna , Le Doare Kirsty , Garssen Johan , Hanna Heather , Khaleva Ekaterina , Peroni Diego G , Geddes Donna T , Kozyrskyj Anita L , Warner John O , Munblit Daniel
Published: March 2019

A large number of biologically active components have been found in human milk (HM), and in both human and animal models, studies have provided some evidence suggesting that HM composition can be altered by maternal exposures, subsequently influencing health outcomes for the breastfed child. Evidence varies from the research studies on whether breastfeeding protects the offspring from noncommunicable diseases, including those associated with immunological dysfunction. It has been hypothesized that the conflicting evidence results from HM composition variations, which contain many immune active molecules, oligosaccharides, lactoferrin, and lysozyme in differing concentrations, along with a diverse microbiome. Determining the components that influence infant health outcomes in terms of both short- and long-term sequelae is complicated by a lack of understanding of the environmental factors that modify HM constituents and thereby offspring outcomes. Variations in HM immune and microbial composition (and the differing infantile responses) may in part explain the controversies that are evidenced in studies that aim to evaluate the prevalence of allergy by prolonged and exclusive breastfeeding. HM is a “mixture” of immune active factors, oligosaccharides, and microbes, which all may influence early immunological outcomes. This comprehensive review provides an in-depth overview of existing evidence on the studied relationships between maternal exposures, HM composition, vaccine responses, and immunological outcomes.
Effects of weight-neutral approaches compared with traditional weight-loss approaches on behavioral, physical, and psychological health outcomes: a systematic review and meta-analysis
Authors: Dugmore Jaslyn A , Winten Copeland G , Niven Hannah E , Bauer Judy
Published: March 2019

Context

Weight-neutral approaches for health are emerging therapeutic alternatives to traditional weight-loss approaches. The existing literature base comparing these approaches has not yet been systematically evaluated by a meta-analysis.

Objective

This review aims to determine if weight-neutral approaches are valid alternatives to weight-loss approaches for improving physical, psychological, and behavioral health outcomes.

Data Sources

Embase, Scopus, PsycINFO, PubMed, CINAHL, and the University of Queensland Library databases were searched.

Study Selection

Peer-reviewed, experimental, or quasi-experimental studies that included weight-neutral and weight-loss arms and reported physical, psychological, or behavioral outcomes were eligible. A total of 525 studies were identified through initial database searches, with 10 included in the final analysis after exclusion criteria were applied.

Data Extraction

Screening and eligibility assessment of studies followed the PRISMA protocol. The following outcomes were extracted: weight, body mass index, lipid and glucose variables, blood pressure, eating behavior, self-esteem, depression, quality of life, physical activity, and diet quality.

Data Analysis

Studies were graded per the National Health and Medical Research Council (NHMRC) level-of-evidence tool and the Academy of Nutrition and Dietetics quality-evaluation tool. Effect sizes were examined as a meta-analysis of standardized and mean differences using a random-effects inverse-variance model with 95%CIs. Practice recommendations for each outcome were graded per NHMRC body-of-evidence guidelines.

Conclusions

Weight-neutral approaches resulted in greater improvement in bulimia (P = 0.02), but no significant differences were observed for any other outcome. Weight-neutral approaches may be as effective as weight-loss methods for improving physical, psychological, and behavioral outcomes. Limitations include inconsistent definitions of both approaches and variable time frames of follow-up.
Terms-of-trade and counterterrorism externalities
Authors: Bandyopadhyay Subhayu , Sandler Todd , Younas Javed
Published: March 2019

This article investigates the interplay of trade and terrorism externalities under free trade between a developed nation that exports a manufactured good to and imports a primary product from a developing nation. A terrorist organization targets both nations and reduces its attacks in response to a nation’s defensive counterterrorism efforts, while transferring some of its attacks abroad. Terms-of-trade considerations lead the developed nation to raise its counterterrorism level beyond the ‘small-country’ level, thus compounding its overprovision of these measures. By contrast, the developing nation limits its defensive countermeasures below that of the small-country level. This asymmetry is a novel finding. The analysis is extended to include proactive countermeasures to weaken the terrorist group. Again, the developed country raises its efforts owing to the terms-of-trade externality, which now opposes the underprovision associated with proactive efforts. A second extension allows for several developing-country exporters of the primary product.
Simulation of Dural Repair in Minimally Invasive Spine Surgery With the Use of a Perfusion-Based Cadaveric Model
Authors: Buchanan Ian A , Min Elliot , Pham Martin H , Donoho Daniel A , Bakhsheshian Joshua , Minneti Michael , Zada Gabriel , Giannotta Steven L , Hsieh Patrick C , Liu John C
Published: March 2019

BACKGROUND AND IMPORTANCE

In an era of curtailed work hours and concerns over achieving technical proficiency in the repertoire of procedures necessary for independent practice, many residencies have turned to model simulation as an educational adjunct. Cerebrospinal fluid (CSF) leak repair after inadvertent durotomy in spine surgery is a fundamental skillset for any spine surgeon. While primary closure with suture is not always necessary for small durotomies, larger defects, on the other hand, must be repaired. However, the dire consequences of inadequate repair dictate that it is generally performed by the most experienced surgeon. Few intraoperative opportunities, therefore, exist for CSF leak repair by trainees.

OBJECTIVE

To simulate dural repair in spine surgery using minimal-access techniques.

METHODS

A cohort of 8 neurosurgery residents was evaluated on their durotomy repair efforts in a perfusion-based cadaveric model.

RESULTS

Study participants demonstrated consistent improvement across trials, with a significant reduction in closure times between their initial (12 min, 7 sec ± 4 min, 43 sec) and final attempts (7 min, 4 sec ± 2 min, 6 sec; P = .02). Moreover, all trainees—irrespective of postgraduate year—were able to accomplish robust dural closures resistant to simulated Valsalva maneuvers. Participants reported high degrees of model realism and exhibited significant increases in postprocedure confidence scores.

CONCLUSION

Our results support use of perfusion-based simulation models as a complement to neurosurgery training, as it affords unrestricted opportunities for honing psychomotor skillsets when resident learning is increasingly being challenged by work-hour limitations and stricter oversight in the context of value-based healthcare.
Surgical Outcomes in Post-Traumatic Epilepsy: A Single Institutional Experience
Authors: Hitti Frederick L , Piazza Matthew , Sinha Saurabh , Kvint Svetlana , Hudgins Eric , Baltuch Gordon , Diaz-Arrastia Ramon , Davis Kathryn A , Litt Brian , Lucas Timothy , Chen H Isaac
Published: March 2019

BACKGROUND

Post-traumatic epilepsy (PTE) is a debilitating sequela of traumatic brain injury (TBI), occurring in up to 20% of severe cases. This entity is generally thought to be more difficult to treat with surgical intervention.

OBJECTIVE

To detail our experience with the surgical treatment of PTE.

METHODS

Patients with a history of head injury undergoing surgical treatment for epilepsy were retrospectively enrolled. Engel classification at the last follow-up was used to assess outcome of patients that underwent surgical resection of an epileptic focus. Reduction in seizure frequency was assessed for patients who underwent vagal nerve stimulator (VNS) or responsive neurostimulator (RNS) implantation.

RESULTS

A total of 23 patients met inclusion criteria. Nineteen (82.6%) had mesial temporal sclerosis, 3 had lesional neocortical epilepsy (13.0%), and 1 had nonlesional neocortical epilepsy (4.3%). Fourteen patients (60.9%) underwent temporal lobectomy (TL), 2 underwent resection of a cortical focus (8.7%), and 7 underwent VNS implantation (30.4%). Three patients underwent RNS implantation after VNS failed to reduce seizure frequency more than 50%. In the patients treated with resection, 11 (68.8%) were Engel I, 3 (18.8%) were Engel II, and 2 (12.5%) were Engel III at follow-up. Average seizure frequency reduction in the VNS group was 30.6% ± 25.6%. RNS patients had reduction of seizure severity but seizure frequency was only reduced 9.6% ± 13.6%.

CONCLUSION

Surgical outcomes of PTE patients treated with TL were similar to reported surgical outcomes of patients with nontraumatic epilepsy treated with TL. Patients who were not candidates for resection demonstrated variable response rates to VNS or RNS implantation.
The attachment of a settlor’s rights under Liechtenstein Law
Authors: Nigg Thomas , Vogt Domenik
Published: March 2019

Settlors regularly want to reserve extensive powers over the assets contributed to a trust. However, this bears the risk that the trust is more vulnerable to attacks from the settlor’s creditors. Thus, setting up a trust frequently involves striking a balance between the reservation of rights and asset protection. In an unprecedented case, the Liechtenstein Supreme Court recently dealt with the question of whether the rights of the settlor of a Liechtenstein trust were attachable. The Supreme Court came to the conclusion that the rights of the debtor, who acted as settlor, protector, and beneficiary of the trust in question, could be attached collectively pursuant to Article 242 of the Liechtenstein Act on Enforcement dated 24 November 1971 (Exekutionsordnung, ‘EO’). This article summarizes and analyses the main considerations of the Liechtenstein Supreme Court and discusses possible ways of structuring Liechtenstein trusts so as to ensure the protection of the trust assets from potential creditor clawbacks.
Impact of formaldehyde addition to spray-dried plasma on functional parameters and animal performance1
Authors: Campbell Joy M , Crenshaw Joe D , Polo Javier , Mellick Dillon , Bienhoff Mark , Stein Hans H
Published: March 2019

Experimental objectives of this study were to determine effects of formaldehyde treatment on the chemical composition of spray-dried plasma (SDP) and to test the hypothesis that growth performance of pigs fed formaldehyde-treated diets containing SDP or diets containing formaldehyde-treated SDP is not reduced compared with pigs fed untreated control diets. Sal CURB ASF liquid antimicrobial and CURB RM Extra liquid mold inhibitor (Kemin Industries, Des Moines, IA) were applied on SDP at 0.1% or 0.3% to determine effects of the products on chemical and functional properties of SDP. Regardless of product, there were no changes in SDP for analyzed protein, ash, pH, or moisture concentration, but IgG concentration in SDP was decreased 8% and 24%, respectively, for 0.1% and 0.3% inclusion of Sal CURB or CURB RM. Two feeding studies using weaned pigs were conducted to determine effects of formaldehyde applied at 0.3% to SDP (experiment 1) or 0.3% to a complete diet containing 5% SDP (experiment 2). Experiment 1 pigs (n = 265) were weaned at 20 ± 2 d of age and allotted to five treatment groups. Experiment 2 pigs (n = 135) were weaned in two groups at 20 ± 2 d of age and allotted to three treatments groups. In experiment 1, the untreated control diet contained soy protein concentrate (SPC) and test diets contained 2.5% or 5.0% SDP without or with formaldehyde treatment. In experiment 2, formaldehyde was applied to a diet containing 5% SDP and an untreated SPC control diet and an untreated diet containing 5% SDP were also included in the experiment. In experiment 1, linear increases (P < 0.05) in average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F) were observed as SDP was included in the diets and the relative bioavailability of formaldehyde-treated SDP was 62% (P = 0.018) if calculations were based on ADG and 15% (P = 0.031) if calculations were based on ADFI. In experiment 2, pigs fed the SDP diet untreated or treated with formaldehyde had increased (P < 0.05) final body weight, ADG, ADFI, and G:F compared with pigs fed the control diet. However, formaldehyde treatment of the plasma-containing diet did not affect pig growth performance compared with pigs fed the untreated SDP diet. In conclusion, formaldehyde treatment applied directly on SDP affects analyzed concentrations of IgG and reduces growth rate of pigs. Treating a complete diet containing 5% SDP with formaldehyde did not affect pig growth performance, and pigs fed diets containing SDP had improved growth performance than those fed the control diet without SDP.
Evaluation of the protective effects of zinc butyrate in IPEC-J2 cells and grower pigs under heat stress1
Authors: Mani Venkatesh , Rubach Jon K , Sanders David J , Pham Thoai , Koltes Dawn A , Gabler Nicholas K , Poss Mitchell J
Published: March 2019

Heat stress (HS) is a major environmental stressor primarily affecting swine performance through negative effects on intestinal health. Zinc and butyric acid supplementation help maintain intestinal integrity and barrier function, and has been shown to be beneficial to swine during stress conditions. We tested a novel formulation of zinc butyrate (ZnB) to study whether it has protective effects toward swine using pig intestinal epithelial cells (IPEC-J2) and in a grower swine HS trial. IPEC-J2 cells were grown either under an inflammatory challenge (Escherichia coli lipopolysaccharide) or HS (41.5 °C for 48 h) using Transwell plates. The tight junction integrity of the cells under various treatments, including ZnB, zinc sulfate, and calcium butyrate, was followed over a period of 36 to 48 h by measuring transepithelial electrical resistance (TER). During inflammatory challenge, ZnB-treated cells had the greatest TER (P < 0.05) at 36 h. When the cells were exposed to HS at 41.5 °C, ZnB-treated cells had similar TER to the cells incubated at 37.0 °C, indicating significant protection against HS. In the swine trial (two dietary treatments, control and an encapsulated form of 40% zinc butyrate [E-ZnB] in hydrogenated palm oil pearls, 12 pigs per treatment), grower gilts (35 ± 1 kg) were supplemented with E-ZnB for 24 d before being subjected to biphasic HS for 7 d, 30 to 32 °C for 8 h and 28 °C for 16 h, for a total duration of 56 h of HS. At the end of the HS phase, half the pigs were euthanized from each treatment (n = 6 per treatment), and growth performance was calculated. During the HS phase, average daily gain (ADG; 0.53 vs. 0.79 kg) and gain-to-feed ratio (G:F; 0.33 vs. 0.43) were greater in the E-ZnB group (P < 0.05). Although in vivo intestinal permeability increased during the HS phase (P < 0.05), no differences were observed in the present study for the intestinal health parameters measured including TER, villus height:crypt depth ratio, and in vivo and ex vivo intestinal permeability between the two treatment groups. In conclusion, results presented here demonstrate that E-ZnB supplementation during HS improves ADG and G:F in grower pigs. Although we could not measure any differences, the mode of action of butyric acid and zinc suggests that the performance improvements are related to improved intestinal health.
Trichothecene-Producing Fusarium Species Isolated from Soybean Roots in Ethiopia and Ghana and their Pathogenicity on Soybean
Authors: Hartman Glen L. , McCormick Susan P. , O’Donnell Kerry
Published: March 2019

Numerous pathogen surveys have reported that diverse Fusarium spp. threaten soybean production in North and South America. However, little research has been conducted to characterize Fusarium pathogens of soybean in sub-Saharan Africa. Our objectives were to (i) identify Fusarium spp. isolated from discolored root segments of soybean grown in Ethiopia and Ghana using DNA sequence data, (ii) determine whether isolates nested in the Fusarium incarnatum-equiseti and F. sambucinum species complexes (FIESC and FSAMSC, respectively) produced trichothecene mycotoxins in vitro, and (iii) test these isolates for pathogenicity on soybean. Molecular phylogenetic analyses revealed that the trichothecene mycotoxin-producing isolates comprised three undescribed species within the FIESC and FSAMSC. Mycotoxin type B trichothecene 4,15-diacetylnivalenol or T-2 toxin and related type A neosolaniol trichothecenes were produced by 18 of the 21 isolates. Of the 12 isolates from Ethiopia and Ghana tested for their impact on seed germination, 5, comprising two undescribed phylospecies (i.e., Fusarium sp. number 3 and Fusarium sp. FIESC 2,) completely inhibited germination, whereas 4 caused no reduction in germination. Root lesions induced by all 12 isolates were greater than the uninoculated negative control. Additional variation among the isolates was reflected in differences (α = 0.05) in lesion lengths, which ranged from 34 to 67% of total root length. This is the first report characterizing FIESC and FSAMSC isolates from soybean roots in Ethiopia and Ghana.
Sacropelvic Fixation With S2 Alar Iliac Screws May Prevent Sacroiliac Joint Pain After Multisegment Spinal Fusion
Authors: Unoki Eiki , Miyakoshi Naohisa , Abe Eiji , Kobayashi Takashi , Abe Toshiki , Kudo Daisuke , Shimada Yoichi
Published: March 2019

Study Design.

A retrospective study.

Objective.

To examine the postoperative incidence of sacroiliac joint pain (SIJP) at the lower fusion level following multisegment fusion.

Summary of Background Data.

Recently, multisegment fusion is being increasingly performed. While proximal junctional kyphosis (PJK) commonly develops following multisegment fusion, SIJP also commonly occurs following this surgery. In surgery for adult spinal deformity, fixation is often extended to the pelvis to include the sacroiliac joint. Therefore, the question of whether SIJP occurs in such cases is interesting. Here, we examined postoperative incidence of SIJP at the lower fusion level, including the incidence of PJK, and postoperative lumbopelvic alignment.

Methods.

Participants included 77 patients who underwent corrective fusion (≥3 segments). Patients were divided into three groups based on the lower fixation end: L5 (L5), S (sacrum), and P (pelvis). In the P group, an S2 alar iliac screw was used. Postoperative incidence of SIJP and PJK in each group was examined along with lumbopelvic parameters.

Results.

SIJP incidence was 16.7%, 26.1%, and 4.2% in the L5, S, and P groups, respectively, indicating the highest value in the S group and a significantly lower value in the P group. PJK incidence was 23.3%, 30.4%, and 29.2% in the L5, P, and S groups, respectively, with no significant differences. Regarding postoperative lumbopelvic parameters, there was no significant difference between the groups; however, lumbar lordosis tended to be better in the P group.

Conclusion.

SIJP incidence was extremely high with fixation to the sacrum, and in the group with fixation to the pelvis, there was hardly any SIJP. Sacropelvic fixation using S2 alar iliac screws could prevent SIJP onset following multisegment fusion.

Level of Evidence: 3
Evidence for Use of Tenofovir in Pregnancy to Prevent Perinatal Transmission of Hepatitis B Infection
Authors: SYLVESTER-ARMSTRONG KENDRA R. , DUFF PATRICK
Published: March 2019

Perinatal transmission of hepatitis B virus continues to be a serious global public health concern. Transmission failures are related to high maternal viremia. Several antiviral therapies reduce maternal viremia around the time of delivery and decrease maternal-to-child-transmission. This chapter is a review of current studies that, ultimately, have provided strong evidence for the efficacy and safety of 3 antiviral drugs in pregnancy—lamivudine, telbivudine and tenofovir. The latter drug is the particular focus of this chapter which will show that tenofovir is the preferred antiviral therapy in pregnant women because of its potency, safety profile, and low risk of resistance.
Association of Retinopathy of Prematurity and Plateau iris
Authors: Nguyen Van , Jwo Kevin , Bhatt Anand , Mosaed Sameh
Published: March 2019

We present a case series describing a unique entity as it relates to plateau iris. There have been many established risk factors for plateau iris, but we present the following cases that describe patients with plateau iris in the setting of prematurity and/or retinopathy of prematurity as well as high myopia or emmetropia. We believe this to be a distinct form of plateau iris resulting from abnormal ciliary body and angle development in the preterm infant. Subjects were treated according to standard of care, with laser peripheral iridotomies, laser iridoplasty, and even glaucoma drainage implants, as indicated.
Foreign-Body Granulomata Caused by Injected Permanent Filler Masquerading as Cutaneous Sarcoidosis
Authors: Scofield-Kaplan Stacy M. , Patel Sagar Y. , Mueller Andrew , Ford W. Cameron , Evers Bret M. , Hogan R. Nick , Mancini Ronald
Published: March 2019

Foreign-body granuloma formation following filler injections is most commonly seen with permanent fillers; these reactions can occur years following the injections and often require either an intralesional steroid injection or surgical excision. The authors present a case of a 75-year-old woman with a history of systemic sarcoidosis previously treated with numerous immunosuppressive medications who was examined for bilateral infraorbital nodules and swelling that were unresponsive to treatment. She underwent a bilateral anterior orbitotomy through a transconjunctival approach with mass excision. The histologic analysis was consistent with foreign-body granulomata juxtaposed to implantable material, specifically ArteFill, which was injected many years prior. There were no separate noncaseating granulomas to suggest sarcoidosis as the underlying etiology. It is important to consider prior filler injections in patients with sarcoidosis who present with subcutaneous nodules as this changes management and may prevent the need for more aggressive immunosuppressive treatment.
Cardiac disorders and structural brain abnormalities are commonly associated with hypospadias in children with neurodevelopmental disorders
Authors: Gazdagh Gabriella E. , Wang Cunyi , McGowan Ruth , Tobias Edward S. , Ahmed S. Faisal
Published: March 2019

The objective of our study was to use an established cohort of boys to investigate common patterns of malformations in those with hypospadias. We performed a retrospective review of the phenotype of participants in the Deciphering Developmental Disorders Study with neurodevelopmental delay and an ‘Abnormality of the genital system’. This group was divided into two subgroups: those with hypospadias and without hypospadias. Associated phenotypes of the two subgroups were compared and analysed. Of the 166 Deciphering Developmental Disorders participants with hypospadias and neurodevelopmental delay, 47 (28%) had cardiovascular and 40 (24%) had structural brain abnormalities. The rate of cardiovascular abnormalities in those with neurodevelopmental delay and genital abnormalities other than hypospadias (N = 645) was lower at 19% (P = 0.001). In addition, structural brain malformations were higher at 24% in the hypospadias group versus 15% in the group without hypospadias (P = 0.002). The constellation of these features occured at a higher rate in the hypospadias group versus the no hypospadias group (P = 0.038). In summary, this is the first study to indicate that cardiovascular and brain abnormalities are frequently encountered in association with hypospadias in children with neurodevelopmental disorders. Not only do these associations provide insight into the underlying aetiology but also they highlight the multisystem involvement in conditions with hypospadias
Intensivists Performed Percutaneous Bicaval Double-Lumen Echo-Guided Extracorporeal Membrane Oxygenation Cannulation at Bedside in Newborns and Children: A Retrospective Analysis
Authors: Moscatelli Andrea , Febbo Francesca , Buratti Silvia , Pezzato Stefano , Bagnasco Francesca , Lampugnani Elisabetta , Nuri Halkawt , Buffelli Francesca , Grasso Chiara , Castagnola Elio
Published: March 2019

Objectives:

To describe a single institution experience on echo-guided percutaneous bicaval double lumen extracorporeal membrane oxygenation cannulation performed at the bedside by intensivists.

Design:

Retrospective observational study.

Setting:

Extracorporeal membrane oxygenation team of a tertiary care children’s hospital.

Patients:

All patients 0–14 years old undergoing venovenous extracorporeal membrane oxygenation from January 1, 2013, to January 1, 2018.

Interventions:

None.

Measurements and Main Results:

Thirty children underwent 32 extracorporeal membrane oxygenation runs. Median age at enrollment was 2 months (interquartile range, 0–20.5 mo), 65.6% of the runs (21 patients) were performed in newborns (n = 13, 40.6%) or infants (n = 8, 25%). Median preextracorporeal membrane oxygenation index was 66.9 (interquartile range, 50–85.6). Major comorbidities were present in 50% of patients. All patients were cannulated percutaneously. In two cases cannulation occurred from the left internal jugular vein. Extracorporeal membrane oxygenation was effective in increasing pH, arterial oxygen saturation, Pao
2, and lowering Paco
2. The overall differences in pre and postextracorporeal membrane oxygenation values were statistically significant, while stratifying patients according to the cannula diameter (mm)/major diameter of the cannulated internal jugular vein (mm) ratio (> 0.67 or ≤ 0.67), statistical significance was reached only for the highest ratio. Complications were observed in three runs: two cannula tip dislocations in the right atrium and one limited flow in the only case in which an Avalon cannula was not used. In 20 cases (62.5% of 32 runs), the cannulated vessel was patent at follow-up or autopsy. A ratio less than or equal to 0.67 or greater than 0.67 did not influence the occurrence rate of complications, nonpatency of the internal jugular vein, death for intracranial bleeding and death at 30 days from extracorporeal membrane oxygenation discontinuation. Overall cumulative survival at 30 days from extracorporeal membrane oxygenation discontinuation was 60% (95% CI, 40–75), with a survival advantage in the case of ratio greater than 0.67 (65%; 95% CI, 44–80 vs 25%; 95% CI, 0–60).

Conclusions:

The described technique proved to be feasible, safe, and effective. Further investigation is needed.
The New Public Health Workforce: Employment Outcomes of Public Health Graduate Students
Authors: Krasna Heather , Kornfeld Julie , Cushman Linda , Ni Shuyue , Antoniou Pantelis , March Dana
Published: March 2019

Context:

Much has been written about the public health workforce, but very little research has been published—and none in a peer-reviewed journal or other report since 1992—regarding the employment outcomes and employment sectors of graduate students pursuing public health as an area of study.

Objectives:

Our objectives were to review the literature and analyze data regarding the employment outcomes of public health graduate students and to examine how public health schools and programs might respond to changes in the sectors hiring their graduates.

Design:

We reviewed the literature regarding the employment of public health graduates; analyzed 5 years of graduate outcomes from Columbia University's Mailman School of Public Health using logistic regression; and we examined data collected by the Association of Schools & Programs of Public Health.

Participants:

The study included data from surveys of 2904 graduates of Columbia University's Mailman School of Public Health, across 5 graduating cohort years, for whom there were employment sector data available for 1932.

Results:

Much of the research on the public health workforce has defined it as governmental public health. Across each of 5 graduating classes from Columbia University's Mailman School of Public Health, the odds of for-profit sector employment increased by 23% (2012-2016), while hiring by government agencies declined or remained flat. Publicly available employment data from the Web sites of schools of public health and from surveys by the Association of Schools & Programs of Public Health show that hiring of new graduates by for-profit corporations now either closely matches or exceeds governmental hiring at many schools of public health.

Conclusions:

Public health graduates are increasingly working outside of government, and additional analyses are required to determine whether core competencies of public health curricula reflect the needs of the employers that are hiring public health graduates today. Schools and programs of public health should invest in their career services offices and gather input from employers that are currently hiring their graduates, especially as the sectors hiring them may be changing.
Polygenic risk score for Alzheimer’s disease and trajectories of cardiometabolic risk factors in children
Authors: Korologou-Linden Roxanna S , O’Keeffe Linda , Howe Laura D , Smith George Davey , Jones Hannah , Anderson Emma L , Stergiakouli Evie
Published: March 2019

INTRODUCTION

Cardiometabolic factors are implicated in the aetiology of Alzheimer’s disease and may lie on the pathways linking genetic variants to Alzheimer’s disease across the life course. We examined whether polygenic risk scores (PRS) were associated with cardiometabolic health indicators through childhood and adolescence.

METHODS

In 7,977 participants from the Avon Longitudinal Study of Parents and Children, we tested whether a PRS for Alzheimer’s disease was associated with trajectories of cardiometabolic risk factors. We examined trajectories for height 1-18 years; lean and fat mass 9-18 years; systolic and diastolic blood pressure 7-18 years; glucose and C-reactive protein 9-18 years; insulin 10-18 years; high and low-density lipoproteins and triglycerides birth-18 years. We also examined birthweight, interleukin-6 (IL-6) at age 9 years and physical activity at ages 11, 12, and 15 years.

RESULTS

No consistent associations were observed between the PRS excluding genetic variants in the apolipoprotein E (ApoE) gene region and cardiometabolic factors trajectories across childhood and adolescence.

CONCLUSION

We did not detect evidence to suggest that the PRS for Alzheimer’s disease acts through childhood and adolescent cardiometabolic risk factors. Further studies should examine whether these associations emerge later in adulthood when variation in cardiometabolic risk factors is likely to be greater.
Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD)
Authors: Cole Eleanor J. , Stimpson Katy H. , Bentzley Brandon S. , Gulser Merve , Cherian Kirsten , Tischler Claudia , Nejad Romina , Pankow Heather , Choi Elizabeth , Aaron Haley , Espil Flint M. , Pannu Jaspreet , Xiao Xiaoqian , Duvio Dalton , Solvason Hugh B. , Hawkins Jessica , Guerra Austin , Jo Booil , Raj Kristin S. , Debattista Charles , Keller Jennifer , Schatzberg Alan F. , Sudheimer Keith D. , Williams Nolan R.
Published: March 2019

Background

Current treatments for depression are limited by suboptimal efficacy, delayed response, and frequent side effects. Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation treatment that is FDA-approved for treatment-resistant depression (TRD). Recent methodological advancements suggest iTBS could be improved through 1) treating with multiple sessions per day at optimally-spaced intervals, 2) applying a higher overall pulse-dose of stimulation and 3) precision targeting of the left dorsolateral prefrontal cortex (L-DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. We examined the feasibility, tolerability, and preliminary efficacy of an accelerated, high-dose, resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for TRD termed ‘Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)’.

Methods

Twenty-one participants with TRD received open-label SAINT. FcMRI was used to individually target the region of L-DLPFC most anticorrelated with sgACC. Fifty iTBS sessions (1800 pulses per session, 50-minute inter-session interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT.

Results

Nineteen of 21 participants (90.48%) met criteria for remission (≤10 on the Montgomery-Åsberg Depression Rating Scale) immediately after SAINT. Neuropsychological testing demonstrated no negative cognitive side-effects. There were no seizures or other severe adverse events.

Discussion

Our accelerated, high-dose, iTBS protocol with fcMRI-guided targeting (SAINT) was well tolerated and safe. Efficacy was strikingly high, especially for this treatment-resistant population. Double-blinded sham-controlled trials are required to confirm the high remission rate found in this initial study.

Trial registration

ClinicalTrials.govNCT03240692
Genetic Testing Preferences and Intentions in U.S. Patients with Clinically Diagnosed Familial Hypercholesterolemia
Authors: Wand Hannah , Sturm Amy C. , Erby Lori , Kindt Iris , Klein William M. P.
Published: March 2019

Purpose

Familial Hypercholesterolemia (FH) is a common Mendelian disorder characterized by elevated LDL cholesterol levels, which if untreated can cause premature heart disease. Less than 10% of cases in the US are diagnosed, and uptake of genetic testing is suboptimal. This study investigates decisionmaking factors associated with intentions to have FH genetic testing among patients clinically diagnosed with FH.

Methods

Clinically diagnosed adults with FH and no genetic testing were recruited through the FH Foundation and lipid clinics. Participants completed a survey containing items capturing various reasons to engage in genetic testing.

Results

Exploratory factor analysis of survey items identified three factors: (1) aversion to FH genetic information, (2) curiosity regarding medical/family history, (3) and psychological reassurance. Psychological reassurance was, in turn, the only significant predictor of genetic testing intentions. The effect of reassurance was qualified by aversion such that the inverse association between aversion and genetic testing intentions was greater among those with low perceived reassurance.

Conclusion

Findings suggest that clinically diagnosed patients’ decisions about FH genetic testing are driven principally by psychological reassurance.
Increasing global heterogeneity in the life expectancy of older populations
Authors: Joe William , Liou Lathan , Subramanian S V
Published: March 2019

With overall global improvements in life expectancy, one important concern is whether there is cross-country convergence in life expectancy at various ages. Insights in convergence patterns can help realign research priorities help governments better structure health investments across various age groups. We reveal global patterns in life expectancy improvements and identify convergent clubs in life expectancy at various ages for 201 countries / areas between 1950 and 2015. In the case of life expectancy at younger ages, most countries are moving in the same direction, but we observe significant cross-country variation for older adults and the elderly. Further, we observe increasing variance in life expectancy for older adults and elderly across countries. Increasing global heterogeneity in survival experience of older adults and the elderly population thus has remained a neglected aspect in the discussions on global life expectancy improvements. Data, research and policy focus beyond life-expectancy at birth is therefore critical to accelerate survival gains among older adults and elderly, particularly from the developing world.
Multivariate Genome-wide Association Analyses Reveal the Genetic Basis of Seed Fatty Acid Composition in Oat (Avena sativaL.)
Authors: Carlson Maryn O. , Montilla-Bascon Gracia , Hoekenga Owen A. , Tinker Nicholas A. , Poland Jesse , Baseggio Matheus , Sorrells Mark E. , Jannink Jean-Luc , Gore Michael A. , Yeats Trevor H.
Published: March 2019

Oat (Avena sativaL.) has a high concentration of oils, comprised primarily of healthful unsaturated oleic and linoleic fatty acids. To accelerate oat plant breeding efforts, we sought to identify loci associated with variation in fatty acid composition, defined as the types and quantities of fatty acids. We genotyped a panel of 500 oat cultivars with genotyping-by-sequencing and measured the concentrations of ten fatty acids in these oat cultivars grown in two environments. Measurements of individual fatty acids were highly correlated across samples, consistent with fatty acids participating in shared biosynthetic pathways. We leveraged these phenotypic correlations in two multivariate genome-wide association study (GWAS) approaches. In the first analysis, we fitted a multivariate linear mixed model for all ten fatty acids simultaneously while accounting for population structure and relatedness among cultivars. In the second, we performed a univariate association test for each principal component (PC) derived from a singular value decomposition of the phenotypic data matrix. To aid interpretation of results from the multivariate analyses, we also conducted univariate association tests for each trait. The multivariate mixed model approach yielded 148 genome-wide significant single-nucleotide polymorphisms (SNPs) at a 10% false-discovery rate, compared to 129 and 73 significant SNPs in the PC and univariate analyses, respectively. Thus, explicit modeling of the correlation structure between fatty acids in a multivariate framework enabled identification of loci associated with variation in seed fatty acid concentration that were not detected in the univariate analyses. Ultimately, a detailed characterization of the loci underlying fatty acid variation can be used to enhance the nutritional profile of oats through breeding.
Spatiotemporal dynamics of synthetic microbial consortia in microfluidic devices
Authors: Alnahhas Razan N. , Winkle James J. , Hirning Andrew J. , Karamched Bhargav , Ott William , Josić Krešimir , Bennett Matthew R.
Published: March 2019

Synthetic microbial consortia consist of two or more engineered strains that grow together and share the same resources. When intercellular signaling pathways are included in the engineered strains, close proximity of the microbes can generate complex dynamic behaviors that are difficult to obtain using a single strain. However, when a consortium is not cultured in a well-mixed environment the constituent strains passively compete for space as they grow and divide, complicating cell-cell signaling. Here, we explore the temporal dynamics of the spatial distribution of consortia co-cultured in microfluidic devices. To do this, we grew two different strains ofEscherichia coliin microfluidic devices with cell-trapping regions (traps) of several different designs. We found that the size and shape of the traps are critical determinants of spatiotemporal dynamics. In small traps, cells can easily signal one another but the relative proportion of each strain within the trap can fluctuate wildly. In large traps, the relative ratio of strains is stabilized, but intercellular signaling can be hindered by distances between cells. This presents a trade-off between the trap size and the effectiveness of intercellular signaling, which can be mitigated by controlling the initial seeding of cells in the large trap. These results show how synthetic microbial consortia behave in microfluidic traps and provide a method to help remedy the spatial heterogeneity inherent to different trap geometries.
Phylogeography and Evolutionary analysis of African Rotavirus A genotype G12 reveals district genetic diversification within Lineage III
Authors: Motayo Babatunde Olanrewaju , Oluwasemowo Olukunle , Olusola Babatunde Adebiyi , Opayele Adewale Victor , Faneye Adedayo Omotayo
Published: March 2019

Rotavirus genotype G12 has become one of the most prevalent genotypes of rotavirus in Africa. To understand the drivers for its genetic diversity we investigated the Bayesian phylogeney, evolution and population demography of the genotype G12 Africa. Rotavirus genotype G12, VP7 sequences were downloaded and aligned from twelve African countries (n=96). Phylogenetic analysis, Evolutionary analysis and Bayesian Phylogeography was carried out, using MEGA Vs 6, BEAST, and SPREAD3. Phylogeny showed that all the African sequences fell into lineage III diversifying into two major clades. The evolutionary rate was 1.678×10-3(95%HPD, 1.201×10-3-2.198×10-3) substitutions/ site/ year. The MCC tree topology clustered into three lineages (II, III, IV), African strains diversified into three clusters within lineage III. South Africa was the epicentre of viral dispersal. This study shows the potential for genetic diversification of Rotavirus G12 in Africa, continuous molecular surveillance across Africa is recommended to help control effort.

Highlights

Our study revealed that African G12 rotaviruses have diversified into 3 clades within their parental lineage III based on geographic boundaries.

Nigeria was identified Nigeria as country of origin, while South Africa served as the epicentre of dispersal of the genotype across Africa.

We also discovered that they have a constant demographic profile. Our findings reveal the potential for rapid genetic diversity of Rotavirus G12 and highlight the importance of molecular surveillance in Rotavirus control effort.
Inhibition of the Dead Box RNA Helicase 3 prevents HIV-1 Tat and cocaine-induced neurotoxicity by targeting microglia activation
Authors: Aksenova Marina , Sybrandt Justin , Cui Biyun , Sikirzhytski Vitali , Ji Hao , Odhiambo Diana , Lucius Matthew D. , Turner Jill R. , Broude Eugenia , Peña Edsel , Lizarraga Sofia , Zhu Jun , Safro Ilya , Wyatt Michael D , Shtutman Michael
Published: March 2019

HIV-1 Associated Neurocognitive Disorder (HAND) is commonly seen in HIV-infected patients. Viral proteins including Tat cause neuronal toxicity and is worsened by drugs of abuse. To uncover potential targets for anti-HAND therapy, we employed a literature mining system, MOLIERE. Here, we validated Dead Box RNA Helicase 3 (DDX3) as a target to treat HAND via a selective DDX3 inhibitor, RK-33. The combined neurotoxicity of Tat protein and cocaine was blocked by RK-33 in rat and mouse cortical cultures. Transcriptome analysis showed that Tat-activated transcripts include makers and regulators of microglial activation, and RK-33 blocked Tat-induced activation of these mRNAs. Elevated production of proinflammatory cytokines was also inhibited by RK-33. These findings show that DDX3 contributes to microglial activation triggered by Tat and cocaine, and DDX3 inhibition shows promise as a therapy for HAND. Moreover, DDX3 may contribute to the pathology of other neurodegenerative diseases with pathological activation of microglia.
Structure of human cytomegalovirus UL144, an HVEM orthologue, bound to the B and T cell Lymphocyte Attenuator
Authors: Bitra Aruna , Nemčovičová Ivana , Picarda Gaelle , Doukov Tzanko , Wang Jing , Benedict Chris A. , Zajonc Dirk M.
Published: March 2019

Human cytomegalovirus (HCMV) is a β-herpesvirus that has co-evolved with the host immune system to establish lifelong persistence. HCMV encodes many immune-modulatory molecules, including the glycoprotein UL144. UL144 is a structural mimic of the TNFRSF member HVEM, which binds to various ligands LIGHT, LTα, BTLA, CD160 and gD. However, in contrast to HVEM, UL144 selectively binds to only BTLA, inhibiting T cell activation. Here, we report the crystal structure of the UL144/BTLA complex, providing key insights into the molecular mechanisms underlying this virus-host protein interaction. Our structure reveals that UL144 utilizes residues from its N-terminal CRD1 to interact with BTLA in an orientation similar, but not exactly, to that of HVEM. The structural modifications at the CRD1 region of UL144 compared to HVEM have a significant impact on the fine-tuning of BTLA-binding. In addition, the N-terminal CRD2 loop of UL144 is shorter compared to the corresponding region of HVEM, altering the relative orientation of CRD2 with respect to CRD1. Employing structure-guided mutagenesis we have identified a mutant of BTLA (L123A) that interferes with binding to HVEM while preserving interaction towards UL144. Furthermore, our results illuminate structural differences between UL144 and HVEM that explain the inability of UL144 to bind to either LIGHT or CD160. In summary, the specific molecular differences that UL144 has evolved to exclusively target BTLA highlight it as a suitable scaffold for designing superior BTLA agonists that have high potential for potently inhibiting immune responses.

Importance

The co-evolution of HCMV with its host over millions of years has allowed the virus to develop an efficient and specific immune modulatory protein, UL144, that binds exclusively to an immune inhibitory receptor BTLA. The crystal structure of the UL144/BTLA complex presented in this manuscript provides key insights into the molecular mechanisms underlying the virus-host protein interaction. The structure guided mutagenesis revealed select structural hot spots of the UL144/BTLA interaction. The structural details of this viral protein that has evolved to target only BTLA helps in successful design of BTLA agonists to target various T and B cell mediated autoimmune diseases.