bluuebunny/crossref_metadata_2025 huggingface dataset:
Thomae-Weber Formula: Algebraic Computations of Theta Constants
Authors: Celik Turku Ozlum
Published: October 2019

We give an algebraic method to compute the fourth power of the quotient of any even theta constants associated with a given non-hyperelliptic curve in terms of geometry of the curve. In order to apply the method, we work out non-hyperelliptic curves of genus 4, in particular, such curves lying on a singular quadric, which arise from del Pezzo surfaces of degree 1. Indeed, we obtain a complete level 2 structure of the curves by studying their theta characteristic divisors via exceptional divisors of the del Pezzo surfaces as the structure is required for the method.
Impaired Alanine Transport or Exposure to d-Cycloserine Increases the Susceptibility of MRSA to β-lactam Antibiotics
Authors: Gallagher Laura A , Shears Rebecca K , Fingleton Claire , Alvarez Laura , Waters Elaine M , Clarke Jenny , Bricio-Moreno Laura , Campbell Christopher , Yadav Akhilesh K , Razvi Fareha , O’Neill Eoghan , O’Neill Alex J , Cava Felipe , Fey Paul D , Kadioglu Aras , O’Gara James P
Published: October 2019

Prolonging the clinical effectiveness of β-lactams, which remain first-line antibiotics for many infections, is an important part of efforts to address antimicrobial resistance. We report here that inactivation of the predicted d-cycloserine (DCS) transporter gene cycA resensitized methicillin-resistant Staphylococcus aureus (MRSA) to β-lactam antibiotics. The cycA mutation also resulted in hypersusceptibility to DCS, an alanine analogue antibiotic that inhibits alanine racemase and d-alanine ligase required for d-alanine incorporation into cell wall peptidoglycan. Alanine transport was impaired in the cycA mutant, and this correlated with increased susceptibility to oxacillin and DCS. The cycA mutation or exposure to DCS were both associated with the accumulation of muropeptides with tripeptide stems lacking the terminal d-ala-d-ala and reduced peptidoglycan cross-linking, prompting us to investigate synergism between β-lactams and DCS. DCS resensitized MRSA to β-lactams in vitro and significantly enhanced MRSA eradication by oxacillin in a mouse bacteremia model. These findings reveal alanine transport as a new therapeutic target to enhance the susceptibility of MRSA to β-lactam antibiotics.
AKINβ1, a regulatory subunit of SnRK1, regulates organic acid metabolism and acts as a global regulator of genes involved in carbon, lipid and nitrogen metabolism
Authors: Wang You , Wang Liping , Micallef Barry J , Tetlow Ian J , Mullen Robert T , Feil Regina , Lunn John E , Emes Michael J
Published: October 2019

The Sucrose Non-fermenting-1-Related Protein Kinase 1 (SnRK1) is a highly conserved heterotrimeric protein kinase in plants. It possesses a catalytic subunit (α) and two regulatory subunits (β and γ). The effects of altered expression of AKINβ1 on carbohydrate metabolism and gene expression in leaves were investigated in an Arabidopsis T-DNA insertion mutant. The contents of key intermediates in the tricarboxylic acid (TCA) cycle of the mutant leaves were markedly reduced throughout the diurnal cycle, coupled with a decrease in measurable respiration rate. Compared to wild-type, 2485 genes and 188 genes were expressed differentially in leaves of the akinβ1 mutant in response to light and darkness respectively. Among these, several genes exhibited very substantial decreases in expression. Notably, expression of particular isoforms of multigene families involved in malate and lipid metabolism, and nitrate uptake showed decreases of 40-240 fold during the light period, but not during darkness. The subcellular localization of AKINβ1 and the regulatory function of N-myristoylation on the subcellular localization of AKINβ1 were investigated, showing that AKINβ1 localizes to Golgi. A model is hypothesized to explain the effects of AKINβ1 on metabolism and gene expression in Arabidopsis.
Enhancing trehalose biosynthesis improves yield potential in marker-free transgenic rice under drought, saline, and sodic conditions
Authors: Joshi Rohit , Sahoo Khirod Kumar , Singh Anil Kumar , Anwar Khalid , Pundir Preeti , Gautam Raj Kumar , Krishnamurthy S L , Sopory S K , Pareek Ashwani , Singla-Pareek Sneh Lata
Published: October 2019

Marker-free transgenic lines of rice are developed with enhanced trehalose accumulation that is associated with improved grain yield under salinity, sodicity, and drought stresses.
PolyASite 2.0: a consolidated atlas of polyadenylation sites from 3′ end sequencing
Authors: Herrmann Christina J , Schmidt Ralf , Kanitz Alexander , Artimo Panu , Gruber Andreas J , Zavolan Mihaela
Published: October 2019

Generated by 3′ end cleavage and polyadenylation at alternative polyadenylation (poly(A)) sites, alternative terminal exons account for much of the variation between human transcript isoforms. More than a dozen protocols have been developed so far for capturing and sequencing RNA 3′ ends from a variety of cell types and species. In previous studies, we have used these data to uncover novel regulatory signals and cell type-specific isoforms. Here we present an update of the PolyASite (https://polyasite.unibas.ch) resource of poly(A) sites, constructed from publicly available human, mouse and worm 3′ end sequencing datasets by enforcing uniform quality measures, including the flagging of putative internal priming sites. Through integrated processing of all data, we identified and clustered sites that are closely spaced and share polyadenylation signals, as these are likely the result of stochastic variations in processing. For each cluster, we identified the representative - most frequently processed - site and estimated the relative use in the transcriptome across all samples. We have established a modern web portal for efficient finding, exploration and export of data. Database generation is fully automated, greatly facilitating incorporation of new datasets and the updating of underlying genome resources.
Entangled: Evangelicals and Gangs in El Salvador
Authors: Offutt Stephen
Published: October 2019

ow are the two most ubiquitous community-based organizations in poor Salvadoran neighborhoods—gangs and evangelical churches—connected? Most studies concur with the Brenneman/Wolseth thesis, which states that evangelical churches uniquely provide people with a pathway out of gangs. This article argues that such dynamics are a relatively small subset of a broad range of interactions between evangelicals and gangs. Data from the Religion, Global Poverty, and International Development study, collected in a mid-sized Salvadoran city from 2014 to 2018, show that: (1) family networks link evangelicals and gangs; (2) evangelicals and gangs share community governance; (3) gangs infiltrate congregations; and (4) evangelical ideas and networks penetrate gang life. These findings indicate that the widely accepted “haven” perspective of evangelicals in Latin America is insufficient to explain current empirical complexities. An “entanglement” framework is thus introduced, which may be relevant to evangelicals’ relationships to contemporary Latin American society more broadly.
The Rice Microbiome: A Model Platform for Crop Holobiome
Authors: Kim Hyun , Lee Yong-Hwan
Published: October 2019

The plant microbiome, the consortium of microbes surrounding a plant, has potential for improving crop productivity and sustainability. Despite the necessity of agriculturally applicable microbiomes, plant microbiome studies have been conducted in noncrop plants because of the relative easiness of research. However, in order to make plant microbiomes useful for agriculture, a crop plant-based model is needed. In parallel, overlooked parts of microbiomes other than the bacteria-centered research need to be considered to expand our understandings on microbiomes to the ecosystem level. Beyond the microbial composition, functional properties of microbiomes over time and space will help us to select appropriate microbes that can support crop plants by providing stage-specific functions. Less explored communities such as fungi and protists also can provide novel insights on compositional and functional dynamics of each community, including interkingdom or multitrophic interactions. Finally, identification of host factors on functional microbiomes using genetic information of both the host and the microbiomes will shift host-centered breeding to parallel breeding of host and microbiome. This review will give basic and collective information on the rice microbiome and foster the establishment of a crop plant-based model to meet agricultural needs.
30-Day Postoperative Morbidity and Readmission Following Revision Anterior Cervical Discectomy and Fusion (ACDF)
Authors: Malik Azeem T. , Khan Safdar N. , Kim Jeffery , Yu Elizabeth
Published: October 2019

Study Design:

This was a retrospective cohort study.

Objective:

To analyze risk factors associated with 30-day adverse outcomes and readmissions after revision anterior cervical discectomy and fusion (ACDF).

Summary of Background Data:

No current literature has evaluated the risk factors associated with adverse outcomes after revision ACDF.

Methods:

The 2012–2016 American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database was queried using Current Procedural Terminology codes for ACDF (22551, 22554, and 63075) combined with Current Procedural Terminology codes 22830 (exploration of spinal fusion) or 22855 (removal of anterior instrumentation) to identify revision cases. Patients undergoing concurrent posterior cervical spine surgery and/or corpectomies were excluded from the analysis. A total of 1140 patients were retrieved for analysis.

Results:

Out of a total of 1140 patients, 51 (4.5%) experienced at least 1 any adverse event, with 40 (3.5%) experiencing a severe adverse event, and 17 (1.5%) experiencing a minor adverse event. A 30-day readmission rate was 3.4% (N=39) after a revision ACDF. On multivariate analysis, any adverse events were significantly associated with male sex [odds ratio (OR), 1.98], 2-level versus 1-level fusion (OR, 2.05), and a length of stay (LOS)>1 day (OR, 7.70). Severe adverse events were independently associated with male sex (OR, 2.85), smoking (OR, 0.33), 2-level versus 1-level fusion (OR, 2.03), and LOS>1 day (OR, 7.28). LOS>1 day was the only significant factor associated with an minor adverse event (OR, 14.65) and readmission within 30 days (OR, 2.67).

Conclusions:

Using a national surgical database, the study is the first of its kind to report rates and risk factors associated with adverse outcomes after ACDFs. Providers should understand the need of preoperative risk stratification in these patients to reduce the risk of experiencing adverse outcomes.

Level of Evidence:

Level III—retrospective.
Ruxolitinib as monotherapy in a patient with anaplastic lymphoma kinase positive lung adenocarcinoma
Authors: Koršić Marta , Muršić Davorka , Badovinac Sonja , Roglić Mihovil , Jakopović Marko , Zupančić Šalek Silva , Samaržija Miroslav
Published: October 2019

We present unusual treatment outcome in a 59-year-old male diagnosed with metastatic lung adenocarcinoma with a very good response to ruxolitinib as monotherapy. In June 2017, this patient was diagnosed with myeloproliferative neoplasm – Janus-associated kinases 2 positive – and in December 2017 ruxolitinib therapy was started. At the same time, patient was diagnosed with lung adenocarcinoma in the left lower lobe with positive anaplastic lymphoma kinase mutation and with right lower lobe metastasis. Because of partial regression of tumor size noted on the computed tomography (CT) scans during tumor investigation, we did not apply any therapy for lung adenocarcinoma. A follow-up CT scan done in March 2018 showed further size reduction of tumor lesion in lower left lobe (91%), while follow-up CT scan done in June 2018 showed further size reduction of tumor lesion in lower right lobe (82%).
Lipoteichoic Acid as a Potential Noninvasive Biomarker of Biofilm in Dialysis Access
Authors: Pai Amy Barton , McGuire Matthew D. , Davidge Karen N. , Dean Michael C. , Costello Gabrielle M. , Souza Ernane , Mukherjee Sushovita , Heung Michael , Yevzlin Alexander S. , Yessayan Lenar T.
Published: October 2019

Tunneled central venous catheters (TCVCs) are colonized by Gram-positive organisms and form biofilm. Lipoteichoic acid (LTA) is a Gram-positive cell wall component that can be measured in serum. The purpose of this pilot study was to characterize LTA concentrations in hemodialysis (HD) patients with TCVCs compared to other access types and to evaluate biofilm morphology and microbiology in TCVCs removed by clinical decision. The study enrolled patients with TCVCs (18), grafts (19), and fistulas (18). Blood samples were collected before HD, at 30 minutes, 2 hours, and end of HD. Catheters removed by clinical decision were evaluated by scanning electron microscopy (SEM) for biofilm morphology, and portions of the catheter were cultured. LTA was detectable in all samples and concentrations increased significantly in all access types during HD (p< 0.05 for all comparisons). Patients with TCVCs that had a >30% increase in LTA concentration from baseline also had the greatest rate of increase (slope) compared to grafts and fistulas (p= 0.03 andp= 0.04, respectively). Catheters removed by clinical decision (n = 7) and examined by SEM had deposition of fibrin. Cultures revealed polymicrobial colonization. TCVCs had the highest rate of increase of LTA during HD. Further studies to determine the source of LTA in patients with AVG and AVF are warranted.
Nutrition in surgical patients: how soon is too soon?
Authors: Khan Muhammad , Latifi Rifat
Published: October 2019

Purpose of review

Preoperative nutrition support has been extensively studied; however, data on the timing of postoperative nutrition initiation are scarce. The current review focuses on the importance of early nutritional support in surgical patients and their impact on outcomes.

Recent findings

Early nutrition support during the postoperative course may be the most important step that can be taken toward preventing subsequent malnutrition-related complications. European Society for Parenteral and Enteral Nutrition guidelines recommends early nutrition to improve outcomes after surgery and accelerates the recovery. Moreover, nutritional support should be personalized, and disease process-based.

Existing studies appear to focus mostly on abdominal and gastrointestinal surgery. Further prospective observational and randomized clinical trials across different surgical populations will aid surgeons to better understand how early feeds in either form can reduce morbidity, quality of life, and increase recovery rates.
Sleep–Wake States and Feeding Progression in Preterm Infants
Authors: Park Jinhee , Silva Susan G. , Thoyre Suzanne M. , Brandon Debra H.
Published: October 2019

Background

Previous studies demonstrated a short-term relationship between infant sleep–wake states and oral feeding performance, with state being an indication of infants’ neurobehavioral readiness for feeding. However, the relationship between sleep–wake states and feeding skills has not been evaluated longitudinally during hospitalization.

Objectives

The purpose of this study was to examine preterm infants’ sleep–wake state developmental trajectories and their associations with feeding progression during hospitalization.

Methods

This descriptive and exploratory study was a secondary analysis using data from a longitudinal two-group, randomized controlled trial evaluating the effects of early and late cycled light on health and developmental outcomes among extremely preterm infants who were born ≤28 weeks of gestational age. Sleep–wake states were assessed for two 2-hour interfeeding periods per day (day and night hours), 30 weeks postmenstrual age, and every 3 weeks until discharge. Occurrences of active sleep, quiet sleep, and waking were recorded every 10 seconds. Feeding progression was assessed based on an infant’s postmenstrual age at five milestones: first enteral feeding, full enteral feeding, first oral feeding, half oral feeding, and full oral feeding. Trajectory analyses were used to describe developmental changes in sleep–wake states, feeding progression patterns, and associations between feeding progression and sleep–wake trajectories.

Results

Active sleep decreased while waking, and quiet sleep increased during hospitalization. Two distinct feeding groups were identified: typical and delayed feeding progression. In infants with delayed feeding progression, rates of active and quiet sleep development during the day were delayed compared to those with typical feeding progression. We also found that infants with delayed feeding progression were more likely to be awake more often during the night compared to infants with typical feeding progression.

Discussions

Findings suggest that delays in sleep–wake state development may be associated with delays in feeding progression during hospitalization. Infants with delayed feeding skill development may require more environmental protection to further support their sleep development.
Moderator Effects in Intervention Studies
Authors: Becker Heather , Stuifbergen Alexa K. , Zhang Wenhui , Sales Adam C.
Published: October 2019

Background

Although nursing intervention studies typically focus on testing hypothesized differences between intervention and control groups, moderator variables can reveal for whom or under what circumstances an intervention may be most effective.

Objectives

The aim of the study was to explain and illustrate moderator effects using data from a nursing intervention study to improve cognitive abilities in those with a chronic health condition.

Methods

The sample consisted of 178 individuals with multiple sclerosis participating in an experimental study of a cognitive intervention. General linear models were used for analyses. Interaction terms were created to represent moderator effects on three outcomes: self-reported cognitive abilities, use of memory strategies, and verbal memory performance.

Results

The Charlson comorbidity index significantly moderated the intervention effect on self-perceived cognitive abilities. Years of education significantly moderated the intervention effect on use of memory strategies. Scores on a general self-efficacy measure significantly moderated the intervention effect on the Controlled Verbal Learning Test–Second Edition.

Discussion

These analyses highlight the key role that moderator effects can play in nursing research. Although random assignment to groups can control potentially biasing effects of extraneous differences among individuals in intervention and control groups, those very differences may suggest fruitful avenues for hypothesis generating research about what works best for whom in intervention studies.
Morphologic Patterns and the Correlation With MYD88 L265P, CD79B Mutations in Primary Adrenal Diffuse Large B-Cell Lymphoma
Authors: Chen Zihang , Zou Yan , Liu Weiping , Guan Pujun , Tao Qing , Xiang Chunxiang , Zhang Wenyan , Ye Yunxia , Yan Jiaqi , Zhao Sha
Published: October 2019

Primary adrenal diffuse large B-cell lymphoma (PA-DLBCL) is a rare subtype of extranodal DLBCL. Because of the rarity of this disease, its morphologic and genetic features are not comprehensively studied. Here, we systematically reviewed the clinicopathologic features of 42 cases of PA-DLBCL from our institution and investigated the frequency of MYD88 L265P and CD79B (exon 5) mutation in 29 eligible cases using Sanger sequencing. Clinically, PA-DLBCL was predominant in elderly male patients with advanced clinical stage and poor outcomes. Morphologically, the tumors often showed a sinusoidal and/or cohesive pattern with condensed chromatin and inconspicuous nucleolus which mimicked neuroendocrine carcinoma. Moreover, increased Reed-Sternberg–like cells were observed frequently. These confounding morphologic manifestations may lead to misdiagnosis. Genetically, PA-DLBCL harbored a high prevalence of MYD88 L265P (24%) and CD79B mutations (52%) which may be involved in lymphomagenesis. The CD79B mutation was significantly associated with a worse prognosis. A novel Histo-Molecular Classification system (4 categories) was proposed based on correlation with genetic changes. Generally, the neuroendocrine carcinoma–like type was associated with CD79B mutation, whereas the RS-like cell type indicated MYD88 L265P. The biphasic type was correlated with coexisting mutations of MYD88 and CD79B, whereas the common type implied no mutation. Furthermore, the common type showed significantly better survival. In conclusion, the proposed new category system could indicate the genetic changes as well as facilitate risk stratification to guide treatment and predict prognosis. Although this study augmented our understanding of PA-DLBCL, further analysis is required to validate our results and extend them to extranodal DLBCL at other sites.
The Vital Role of Professionalism in Physical Medicine and Rehabilitation
Authors: Silver Julie K. , Cuccurullo Sara , Weiss Lyn D. , Visco Christopher , Oh-Park Mooyeon , Karimi Danielle Perret , Frontera Walter R. , Fleming Talya K. , Bosques Glendaliz , Bhatnagar Saurabha , Ambrose Anne Felicia , Nguyen Vu Q.C.
Published: October 2019

Professionalism in medicine is universally embraced, and it is the foundation for core competencies in medical education, clinical practice, and research. Physical medicine and rehabilitation physicians must master a complex body of knowledge and use this to responsibly care for patients. Rehabilitation professionals work in various settings; however, each one must establish and maintain ethical standards consistent with the specialty and national standards. For example, the Accreditation Council for Graduate Medical Education lists professionalism as one of its six core competencies, which trainees must master. There is a growing interest in professionalism and some of the ethical issues that it encompasses. This report provides a general overview of professionalism. Future reports are needed, and there is an opportunity to consider many facets of professionalism in greater detail.
The Mediating Effect of Life-style Behaviors on the Association Between Personality Traits and Cardiovascular Disease Mortality Among 29,766 Community-Dwelling Japanese
Authors: Narita Mamoru , Tanji Fumiya , Tomata Yasutake , Mori Kentaro , Tsuji Ichiro
Published: October 2019

Objective

Personality traits have been associated with an increased risk of cardiovascular disease (CVD) mortality as well as life-style–related cardiovascular risk factors. However, the mediating effects of life-style behaviors in the association between personality factors and CVD mortality remain insufficiently understood. The aim of the present study was to examine the mediating effect of life-style behaviors on the association between personality traits and CVD mortality.

Methods

We conducted a prospective cohort study of 29,766 Japanese adults aged 40 to 64 years at the baseline and followed them up for 20.8 years from 1990 to 2011. Personality was measured using the Japanese version of the Eysenck Personality Questionnaire – Revised Short Form in 1990. We estimated the multivariable hazard ratio and 95% confidence interval for CVD mortality using Cox proportional hazards models, and explored the mediating effects of life-style behaviors (smoking, drinking, body mass index, and time spent walking) on the association between personality traits and CVD mortality.

Results

We documented 1033 deaths due to CVD during 562,446 person-years of follow-up. Psychoticism represents tough-mindedness, aggressiveness, coldness, a lack of deliberateness, and egocentricity. After adjusting for confounding variables, higher psychoticism was associated with CVD mortality (base model hazard ratio = 1.36, 95% confidence interval = 1.14–1.61, p trend < .001). All the life-style behaviors together mediated this association by 19.2%, with smoking having the greatest effect at 15.7%. For the other personality traits, no significant associations with CVD mortality were found.

Conclusion

The present study demonstrated that life-style behaviors, especially smoking, partially mediate the association between psychoticism and CVD mortality.
Placebo Effects in the Neuroendocrine System: Conditioning of the Oxytocin Responses
Authors: Skvortsova Aleksandrina , Veldhuijzen Dieuwke S. , Pacheco-Lopez Gustavo , Bakermans-Kranenburg Marian , van IJzendoorn Marinus , Smeets Monique A.M. , Wilderjans Tom F. , Dahan Albert , van den Bergh Omer , Chavannes Niels H. , van der Wee Nic J.A. , Grewen Karen M. , van Middendorp Henriët , Evers Andrea W.M.
Published: October 2019

Objective

There is evidence that placebo effects may influence hormone secretion. However, few studies have examined placebo effects in the endocrine system, including oxytocin placebo effects. We studied whether it is possible to trigger oxytocin placebo effects using a classical conditioning paradigm.

Methods

Ninety-nine women were assigned to a conditioned, control, or drug control group. In the two-phase conditioning paradigm, participants in the conditioned and drug control groups received an oxytocin nasal spray combined with a distinctive smell (conditioned stimulus [CS]) for three acquisition days, whereas the control group received placebo spray. Subsequently, the conditioned and control groups received placebo spray with the CS and the drug control group received oxytocin spray for three evocation days. Salivary oxytocin was measured several times during each day. Pain sensitivity and facial evaluation tests previously used in oxytocin research were also administered.

Results

On evocation day 1, in the conditioned group, oxytocin significantly increased from baseline to 5 minutes after CS (B[slope] = 19.55, SE = 5.88,p< .001) and remained increased from 5 to 20 (B= −10.42, SE = 5.81,p= .071) and 50 minutes (B= −0.70, SE = 3.37,p= .84). On evocation day 2, a trend for increase in oxytocin was found at 5 minutes (B= 15.22, SE = 8.14,p= .062). No placebo effect was found on evocation day 3 (B= 3.57, SE = 3.26,p= .28). Neither exogenous nor conditioned oxytocin affected pain or facial tasks.

Conclusions

Results indicate that oxytocin release can be conditioned and that this response extinguishes over time. Triggering hormonal release by placebo manipulation offers various clinical possibilities, such as enhancing effects of pharmacological treatments or reducing dosages of medications.

Trial Registration:The study was registered as a clinical trial on www.trialregister.nl (number NTR5596).
Decreased growth among antiretroviral drug and HIV-exposed uninfected versus unexposed children in Malawi and Uganda
Authors: Aizire Jim , Sikorskii Alla , Ogwang Lillian Wambuzi , Kawalazira Rachel , Mutebe Alex , Familiar-Lopez Itziar , Mallewa MacPherson , Taha Taha , Boivin Michael J. , Fowler Mary Glenn
Published: October 2019

Objective:

To compare growth among antiretroviral drug and maternal HIV-exposed uninfected (AHEU) versus age-matched and sex-matched HIV-unexposed uninfected (HUU) children.

Design:

Prospective cohort of AHEU children identified from the PROMISE trial (NCT01061151: clinicaltrials.gov registry) and age-matched and sex-matched HUU controls from child-wellness clinics, enrolled (September 2013 to October 2014) in Malawi and Uganda.

Methods:

Weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ), and head-circumference-for-age (HCAZ) z-scores were derived at 12 months and 24 months of age. Wilcoxon Rank-Sum and Fisher's exact tests were used for unadjusted exposure group comparisons. Generalized Estimating Equations models estimated adjusted relative risks (aRR) for poor growth outcomes.

Results:

Overall, 471 (50.5%) AHEU and 462 (49.5%) HUU children were assessed. Ugandan AHEU compared with HUU children had significantly lower mean LAZ (P < 0.001) and WAZ (P < 0.001) at 12 and 24 months of age and HCAZ (P = 0.016) at 24 months, with similar but not significant differences among Malawian AHEU and HUU children. The risk of stunting (more than two standard deviations below the WHO population LAZ median) was increased among AHEU versus HUU children: aRR = 2.13 (95% confidence interval (CI): 1.36–3.33), P = 0.001 at 12 months, and aRR = 1.67 (95% CI 1.16–2.41), P = 0.006 at 24 months of age in Uganda; and aRR = 1.32 (95% CI 1.10–1.66), P = 0.018, at 24 months of age in Malawi. The risk of HCAZ below WHO median was increased among AHEU versus HUU children at 24 months of age, aRR = 1.35 (95% CI 1.02–1.79), P = 0.038 in Uganda; and aRR = 1.35 (95% CI 0.91–2.02), P = 0.139 in Malawi.

Conclusion:

Perinatal exposures to maternal HIV and antiretroviral drugs were associated with lower LAZ (including stunting), WAZ and HCAZ at 24 months of age compared with HUU children.
Effectiveness of Transmitted Drug Resistance Testing Before Initiation of Antiretroviral Therapy in HIV-Positive Individuals
Authors: Lodi Sara , Günthard Huldrych F. , Gill John , Phillips Andrew N. , Dunn David , Vu Quang , Siemieniuk Reed , Garcia Federico , Logan Roger , Jose Sophie , Bucher Heiner C. , Scherrer Alexandra U. , Reiss Peter , van Sighem Ard , Boender T. Sonia , Porter Kholoud , Gilson Richard , Paraskevis Dimitrios , Simeon Metallidis , Vourli Georgia , Moreno Santiago , Jarrin Inmaculada , Sabin Caroline , Hernán Miguel A. ,   on behalf of the HIV-CAUSAL Collaboration
Published: October 2019

Background:

For people living with HIV, major guidelines in high-income countries recommend testing for transmitted drug resistance (TDR) to guide the choice of first-line antiretroviral therapy (ART). However, individuals who fail a first-line regimen can now be switched to one of several effective regimens. Therefore, the virological and clinical benefit of TDR testing needs to be evaluated.

Methods:

We included individuals from the HIV-CAUSAL Collaboration who enrolled <6 months of HIV diagnosis between 2006 and 2015, were ART-naive, and had measured CD4 count and HIV-RNA. Follow-up started at the date when all inclusion criteria were first met (baseline). We compared 2 strategies: (1) TDR testing within 3 months of baseline versus (2) no TDR testing. We used inverse probability weighting to estimate the 5-year proportion and hazard ratios (HRs) of virological suppression (confirmed HIV-RNA <50 copies/mL), and of AIDS or death under both strategies.

Results:

Of 25,672 eligible individuals (82% males, 52% diagnosed in 2010 or later), 17,189 (67%) were tested for TDR within 3 months of baseline. Of these, 6% had intermediate- or high-level TDR to any antiretroviral drug. The estimated 5-year proportion virologically suppressed was 77% under TDR testing and 74% under no TDR testing; HR 1.06 (95% confidence interval: 1.03 to 1.19). The estimated 5-year risk of AIDS or death was 6% under both strategies; HR 1.03 (95% confidence interval: 0.95 to 1.12).

Conclusions:

TDR prevalence was low. Although TDR testing improved virological response, we found no evidence that it reduced the incidence of AIDS or death in first 5 years after diagnosis.
Herpetic Corneal Keratopathy Management Using Ipsilateral Supratrochlear Nerve Transfer for Corneal Neurotization
Authors: Lin Chih-Hung , Lai Li-Ju
Published: October 2019

Background

Neurotrophic keratopathy (NK) is a potentially sight-threatening condition caused by impairment in the trigeminal corneal innervations with decrease or loss of corneal sensitivity. This prospective study aimed to evaluate the outcomes of surgical neurotization of the cornea using ipsilateral supratrochlear nerve transfer in patients with herpes-induced NK.

Methods

An ophthalmologist and a plastic surgeon performed an interdisciplinary corneal neurotization in 13 eyes of 13 patients after preoperative exclusion of forehead sensation impairment. A 3-cm supra-eyebrow incision allowed for microsurgical supratrochlear nerve dissection, and a subconjunctival tunneling was performed for the nerve transfer. Neurotrophic keratopathy was assessed preoperatively and every 3 months postoperatively using slit-lamp microscopy, the corneal sensitivity test, specular microscopy, and in vivo confocal microscopy.

Results

The surgeries had no major complications. The average disease duration from cornea denervation to surgery was 15.2 years. The mean follow-up duration was 18.5 ± 6 months. The symptoms exhibited subjectively improved visual acuity, and objectively improved visual analog scale and NK grading. The subepithelial corneal nerve plexus was found at 9 months postoperatively. The corneal thickness decreased and the corneal endothelial count increased postoperatively.

Conclusions

This is the largest series of corneal neurotization using direct ipsilateral supratrochlear nerve transfer. It is a minimally invasive method to restore corneal sensitivity and treat NK successfully within 1 year without a sural nerve graft. A long-term follow-up is needed for further assessment.
Clinical and Optic Disc Characteristics of Patients Showing Visual Recovery in Leber Hereditary Optic Neuropathy
Authors: Moon Yeji , Kim Ungsoo S. , Han Jinu , Ahn Hyosook , Lim Hyun Taek
Published: October 2019

Background:

The visual prognosis in Leber hereditary optic neuropathy (LHON) is generally poor. However, some individuals can have spontaneous visual recovery (VR) in one or both eyes by a mechanism that is not yet clearly understood. The purpose of this study was to determine whether certain clinical and optic disc features are associated with VR in patients with LHON.

Methods:

We retrospectively examined 80 eyes of 40 patients with LHON using clinical databases, fundus photographs, and high-definition spectral-domain optical coherence tomography (OCT) images. VR was defined as a gain of 3 or more lines of logarithm of the minimum angle of resolution (logMAR)–scaled visual acuity from nadir; this represents a doubling of the visual angle. Patients were divided into VR and nonrecovery (NR) groups. Using fundus photographs, we measured optic disc size and evaluated for the presence of optic disc features, including peripapillary telangiectasia, disc hyperemia, and swelling. We also measured the disc area, cup-to-disc ratio, and rim area of the optic disc using OCT.

Results:

Twenty-one of 80 eyes (26%) had a VR. The VR occurred within 2 years after onset in 81% of cases. The VR group showed younger age at onset (21 vs 29 years, P = 0.017) and better visual acuity at the nadir (1.39 vs 2.16 logMAR, P < 0.001) compared with the NR group. Optic disc features, particularly peripapillary telangiectasia (P = 0.027) and disc hyperemia (P = 0.006), were more prominent in the NR group. The cup-to-disc ratio was significantly smaller (0.64 vs 0.71, P = 0.004) and the rim area was significantly greater (1.17 vs 0.85 mm2, P < 0.001) in the VR group compared with the NR group.

Conclusions:

A younger age at onset and a less severe reduction of visual acuity at the nadir were associated with a higher probability of VR. Presence of peripapillary telangiectasia and optic disc hyperemia may serve as predictive factors for poor visual prognosis in patients with LHON.
Referral Patterns in Neuro-Ophthalmology
Authors: Stunkel Leanne , Mackay Devin D. , Bruce Beau B. , Newman Nancy J. , Biousse Valérie
Published: October 2019

Background:

Neuro-ophthalmologists specialize in complex, urgent, vision- and life-threatening problems, diagnostic dilemmas, and management of complex work-ups. Access is currently limited by the relatively small number of neuro-ophthalmologists, and consequently, patients may be affected by incorrect or delayed diagnosis. The objective of this study is to analyze referral patterns to neuro-ophthalmologists, characterize rates of misdiagnoses and delayed diagnoses in patients ultimately referred, and delineate outcomes after neuro-ophthalmologic evaluation.

Methods:

Retrospective chart review of 300 new patients seen over 45 randomly chosen days between June 2011 and June 2015 in one tertiary care neuro-ophthalmology clinic. Demographics, distance traveled, time between onset and neuro-ophthalmology consultation (NOC), time between appointment request and NOC, number and types of providers seen before referral, unnecessary tests before referral, referral diagnoses, final diagnoses, and impact of the NOC on outcome were collected.

Results:

Patients traveled a median of 36.5 miles (interquartile range [IQR]: 20–85). Median time from symptom onset was 210 days (IQR: 70–1,100). Median time from referral to NOC was 34 days (IQR: 7–86), with peaks at one week (urgent requests) and 13 weeks (routine requests). Median number of previous providers seen was 2 (IQR: 2–4; range:0–10), and 102 patients (34%) had seen multiple providers within the same specialty before referral. Patients were most commonly referred for NOC by ophthalmologists (41% of referrals). Eighty-one percent (242/300) of referrals to neuro-ophthalmology were appropriate referrals. Of the 300 patients referred, 247 (82%) were complex or very complex; 119 (40%) were misdiagnosed; 147 (49%) were at least partially misdiagnosed; and 22 (7%) had unknown diagnoses. Women were more likely to be at least partially misdiagnosed—108 of 188 (57%) vs 39 of 112 (35%) of men (P < 0.001). Mismanagement or delay in care occurred in 85 (28%), unnecessary tests in 56 (19%), unnecessary consultations in 64 (22%), and imaging misinterpretation in 16 (5%). Neuro-ophthalmologists played a major role in directing treatment, such as preserving vision, preventing life-threatening complications, or avoiding harmful treatment in 62 (21%) patients.

Conclusions:

Most referrals to neuro-ophthalmologists are appropriate, but many are delayed. Misdiagnosis before referral is common. Neuro-ophthalmologists often prevent vision- and life-threatening complications.
Protective effects of polygalasaponin F on oxidative stress and apoptosis-induced ischemic myocardial injury in neonatal rats with hypoxic-ischemic brain damage
Authors: Zhou Wen-Li , Zhang Jian-Tao , Xu Wei , Sun Jing-Hui
Published: October 2019

The aim of the present study was to evaluate the role of polygalasaponin F on ischemic myocardial injury in neonatal rats with hypoxic-ischemic brain damage. A primary in-vitro myocardial cell oxygen-glucose deprivation/reperfusion model and an in-vivo middle cerebral artery occlusion model were established. The results demonstrated that polygalasaponin F protects myocardium in hypoxic-ischemic brain injury. The mechanisms of its protective effect involved in (1) reducing oxidant stress injury, (2) reducing the apoptosis rate of myocardial cells through increasing the Bcl-2 protein level and decreasing the Cyt-C and Bax values, and (3) alleviating liver and kidney damage caused by cerebral hypoxia and ischemia via reducing the damage markers. The results of the present study may contribute toward the development of novel strategies for clinical cardioprotection with hypoxic-ischemic brain damage.
Motivational effects on brain activity: need for closure moderates the impact of task uncertainty on engagement-related P3b
Authors: Kossowska Małgorzata , Szwed Paulina , Wyczesany Miroslaw
Published: October 2019

Need for cognitive closure (NFC), that is, individual’s aversion toward uncertainty and the desire to reduce it quickly usually manifests in effort minimizing cognitive strategies. Recent studies, however, demonstrated that it is also linked with laborious processing when the task itself induces uncertainty. Although this pattern was observed when testing behaviors and cardiovascular activity, it has never been tested on a neurocognitive level. To fill this gap, we investigate whether NFC moderates the impact of task uncertainty on engagement-related P3b component of brain activity. In the experiment, we recorded the electroencephalographic activity of the brain while participants performed a sampling task which provides uncertainty manipulation within participants. We also manipulated NFC between participants. As predicted, we did not find any differences between high and low NFC participants in the P3b component at lower levels of uncertainty. However, at the highest level of uncertainty, the P3b component decreases significantly among low but not high NFC participants. That is because gaining certainty and achieving closure is not a critical epistemic goal for low NFC and thus, exerting extra effort to gain certainty is not justified.
Attention shifting and subliminal cueing under high attentional load: an EEG study using emotional faces
Authors: Tipura Eda , Renaud Olivier , Pegna Alan J.
Published: October 2019

Emotional expressions and attentional processes interact such that emotion increases perceptual sensitivity in modality-specific brain areas leading to more efficient processing of the stimulus. In the current study, we asked the question of whether the emotional expressions can be processed subliminally when faces are attended but the emotional expression is irrelevant. We presented angry and neutral male and female faces supraliminally and subliminally to participants in an attention-shifting paradigm. Emotional expression was irrelevant to the task, but the gender of the face was predictive of the location of a subsequent target. Analysis of reaction times revealed that, in the supraliminal condition, targets appearing at validly cued locations produced quicker responses than targets at invalidly cued locations. Target-locked event-related potentials (ERPs) confirmed this result and showed that attention selection elicited higher responses at attended locations, as reflected by the N1 component. However, voluntary attention shifting was not triggered when the cue was not consciously perceived. No effects of emotion were observed following target presentation, suggesting that the high attentional load required by the experiment may have prevented the processing of emotion for undetectable faces, as demonstrated by the fact that, following cue onset, the N170 was modulated by emotion in supraliminal trials only. We therefore show that emotional expressions cannot be processed without awareness when faces are attended, but the emotional expression is irrelevant.
OnabotulinumtoxinA for the treatment of major depressive disorder: a phase 2 randomized, double-blind, placebo-controlled trial in adult females
Authors: Brin Mitchell F. , Durgam Suresh , Lum Arlene , James Lynn , Liu Jeen , Thase Michael E. , Szegedi Armin
Published: October 2019

This 24-week double-blind placebo-controlled multicenter randomized phase 2 trial evaluated efficacy and safety of onabotulinumtoxinA (onabotA; BOTOX) vs. placebo for major depressive disorder (MDD) [NCT02116361]. Primary endpoint was the change in Montgomery-Åsberg Depression Rating Scale (MADRS); secondary endpoints were Clinical Global Impressions-Severity and 17-item Hamilton Depression Rating Scale at week 6. A total of 255 adult females were treated. OnabotA 30 U approached significance compared to placebo on MADRS (mixed-effect model repeated measures least-squares mean difference: −3.7; P = 0.053) and reached significance [least-squares mean differences: −3.6 to −4.2; P < 0.05 (two-sided)] at weeks 3 and 9. Secondary endpoints were also significant at several time points. At week 6, onabotA 50 U did not separate from placebo in any parameters. OnabotA was generally well-tolerated: the only treatment-emergent adverse events reported in ≥5% in either onabotA group, and more than matching placebo were headache, upper respiratory infection, and eyelid ptosis. OnabotA 30 U, administered in a standardized injection pattern in a single session, had a consistent efficacy signal across multiple depression symptom scales for 12 or more weeks. OnabotA 30 U/placebo MADRS differences of (observed ANCOVA) ≥4.0 points (up to week 15) and ≥2.0 points (weeks 18–24) agree with the 2-point change threshold considered clinically relevant in MDD. OnabotA is a local therapy and is not commonly associated with systemic effects of conventional antidepressants and may represent a novel treatment option for MDD.
Anisotropic source modelling for turbulent jet noise prediction
Authors: Xu Xihai , Li Xiaodong
Published: October 2019

An anisotropic component of the jet noise source model for the Reynolds-averaged Navier–Stokes equation-based jet noise prediction method is proposed. The modelling is based on Goldstein's generalized acoustic analogy, and both the fine-scale and large-scale turbulent noise sources are considered. To model the anisotropic characteristics of jet noise source, the Reynolds stress tensor is used in place of the turbulent kinetic energy. The Launder–Reece–Rodi model (LRR), combined with Menter's
ω
-equation for the length scale, with modified coefficients developed by the present authors, is used to calculate the mean flow velocities and Reynolds stresses accurately. Comparison between predicted results and acoustic data has been carried out to verify the accuracy of the new anisotropic source model.

This article is part of the theme issue ‘Frontiers of aeroacoustics research: theory, computation and experiment’.
A phenomenological approach to jet noise: the two-source model
Authors: Tam Christopher K. W.
Published: October 2019

This is a review of the two-source model of jet noise. The model was developed phenomenologically a number of years ago. One of the principal results associated with this model was the identification of two similarity jet noise spectra. This was accomplished through extensive comparisons with a large set of NASA spectrum data. It was found that these two noise spectra when combined appropriately would fit measured noise spectra of jets in any direction regardless of jet temperature and Mach number. Other experimental data in support of the two-source model have since been found. They are discussed in this paper. One of the purposes of this paper is to elaborate on the flow physics of turbulence, noise generation mechanisms and directivity that are the underpinnings of the model. More recent works show the similarity spectra are applicable, well beyond their original database, to noise of military jets, rockets and even volcanoes.

This article is part of the theme issue ‘Frontiers of aeroacoustics research: theory, computation and experiment’.
Simulations of co-axial jet flows on graphics processing units: the flow and noise analysis
Authors: Markesteijn A. P. , Karabasov S. A.
Published: October 2019

Large-eddy simulations (LES) are performed for a range of perfectly expanded co-axial jet cases corresponding to conditions of the computation of coaxial jet noise (CoJeN) experiment by QinetiQ. In all simulations, the high-resolution Compact Accurately Boundary-Adjusting high-REsolution Technique (CABARET) is used for solving the Navier–Stokes equations on unstructured meshes. The Ffowcs Williams–Hawkings method based on the penetrable integral surfaces is applied for far-field noise predictions. To correctly model the turbulent flow downstream of the complex nozzle that includes a central body, a wall modelled LES approach is implemented together with a turbulent inflow condition based on synthetic turbulence. All models are run on graphics processing units to enable a considerable reduction of the flow solution time in comparison with the conventional LES. The flow and noise solutions are validated against the experimental data available with 1–2 dB accuracy being reported for noise spectra predictions on the fine grid. To analyse the structure of effective noise sources of the jets, the covariance of turbulent fluctuating Reynolds stresses is computed and their characteristic scales are analysed in the context of the generalized acoustic analogy jet noise models. Motivated by self-similarity of single-stream axi-symmetric jet flows, a suitable non-dimensionalization of the effective jet noise sources of the CoJeN jets is tested, and its implications for low-order jet noise models are discussed.

This article is part of the theme issue ‘Frontiers of aeroacoustics research: theory, computation and experiment’.