bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographical distribution and habitat characterization of Poa schizantha (Poaceae), a narrow endemic of the coastal sand dunes of the southern Pampas, Argentina
Authors: Celsi Cintia E , Giussani Liliana M
Published: August 2019

Poa schizantha is a dioecious, psammophilous grass endemic to Atlantic coastal dunes in Argentina. We quantified the distribution area of this rare endemic species and characterized its habitat in the southern Pampas region. Convex hull and α-hull methods were used to estimate and map its overall geographical range. Ecological characterization was based on location, environmental variables, floristic composition and vegetation cover. In total, 117 quadrats were sampled in spring. The convex hull (7553 ha) was split, after excluding discontinuities, into two polygons: area 1 (968 ha; a novel area for the species) and area 2 (449 ha) separated by 36 km, indicating two geographically distinct population groups. In active coastal dune fields, P. schizantha occurs mainly in interdune slacks, associated with herbaceous, short, grassland-type vegetation and moist sandy soils with low vegetation cover, suggesting high habitat specificity. Based on TWINSPAN classification and ordination analysis, P. schizantha is related to two main vegetation groups with 100% constancy and c. 30% relative importance: subgroups E (dominated by pioneer dune species) and F (associated with hygrophilous and ubiquitous species). Given the extent of occurrence (restricted to <100 km2) and the severely fragmented habitat condition, we propose the species be categorized as Critically Endangered, following IUCN criteria. Actions aimed towards the survival of this species must prioritize population monitoring and conservation of its dune habitat.
Mutations in CREBBP and EP300 genes affect DNA repair of oxidative damage in Rubinstein-Taybi syndrome cells
Authors: Dutto Ilaria , Scalera Claudia , Tillhon Micol , Ticli Giulio , Passaniti Gianluca , Cazzalini Ornella , Savio Monica , Stivala Lucia A , Gervasini Cristina , Larizza Lidia , Prosperi Ennio
Published: August 2019

Rubinstein-Taybi syndrome (RSTS) is an autosomal-dominant disorder characterized by intellectual disability, skeletal abnormalities, growth deficiency and an increased risk of tumors. RSTS is predominantly caused by mutations in CREBBP or EP300 genes encoding for CBP and p300 proteins, two lysine acetyl-transferases (KAT) playing a key role in transcription, cell proliferation and DNA repair. However, the efficiency of these processes in RSTS cells is still largely unknown. Here, we have investigated whether pathways involved in the maintenance of genome stability are affected in lymphoblastoid cell lines (LCLs) obtained from RSTS patients with mutations in CREBBP or in EP300 genes. We report that RSTS LCLs with mutations affecting CBP or p300 protein levels or KAT activity, are more sensitive to oxidative DNA damage and exhibit defective base excision repair (BER). We have found reduced OGG1 DNA glycosylase activity in RSTS compared to control cell extracts, and concomitant lower OGG1 acetylation levels, thereby impairing the initiation of the BER process. In addition, we report reduced acetylation of other BER factors, such as DNA polymerase β and Proliferating Cell Nuclear Antigen (PCNA), together with acetylation of histone H3. We also show that complementation of CBP or p300 partially reversed RSTS cell sensitivity to DNA damage. These results disclose a mechanism of defective DNA repair as a source of genome instability in RSTS cells.
Cellular and Widefield Imaging of Sound Frequency Organization in Primary and Higher Order Fields of the Mouse Auditory Cortex
Authors: Romero Sandra , Hight Ariel E , Clayton Kameron K , Resnik Jennifer , Williamson Ross S , Hancock Kenneth E , Polley Daniel B
Published: August 2019

The mouse auditory cortex (ACtx) contains two core fields—primary auditory cortex (A1) and anterior auditory field (AAF)—arranged in a mirror reversal tonotopic gradient. The best frequency (BF) organization and naming scheme for additional higher order fields remain a matter of debate, as does the correspondence between smoothly varying global tonotopy and heterogeneity in local cellular tuning. Here, we performed chronic widefield and two-photon calcium imaging from the ACtx of awake Thy1-GCaMP6s reporter mice. Data-driven parcellation of widefield maps identified five fields, including a previously unidentified area at the ventral posterior extreme of the ACtx (VPAF) and a tonotopically organized suprarhinal auditory field (SRAF) that extended laterally as far as ectorhinal cortex. Widefield maps were stable over time, where single pixel BFs fluctuated by less than 0.5 octaves throughout a 1-month imaging period. After accounting for neuropil signal and frequency tuning strength, BF organization in neighboring layer 2/3 neurons was intermediate to the heterogeneous salt and pepper organization and the highly precise local organization that have each been described in prior studies. Multiscale imaging data suggest there is no ultrasonic field or secondary auditory cortex in the mouse. Instead, VPAF and a dorsal posterior (DP) field emerged as the strongest candidates for higher order auditory areas.
Using the Principles of Multisensory Integration to Reverse Hemianopia
Authors: Dakos Alexander S , Jiang Huai , Stein Barry E , Rowland Benjamin A
Published: August 2019

Hemianopia can be rehabilitated by an auditory-visual “training” procedure, which restores visual responsiveness in midbrain neurons indirectly compromised by the cortical lesion and reinstates vision in contralesional space. Presumably, these rehabilitative changes are induced via mechanisms of multisensory integration/plasticity. If so, the paradigm should fail if the stimulus configurations violate the spatiotemporal principles that govern these midbrain processes. To test this possibility, hemianopic cats were provided spatially or temporally noncongruent auditory-visual training. Rehabilitation failed in all cases even after approximately twice the number of training trials normally required for recovery, and even after animals learned to approach the location of the undetected visual stimulus. When training was repeated with these stimuli in spatiotemporal concordance, hemianopia was resolved. The results identify the conditions needed to engage changes in remaining neural circuits required to support vision in the absence of visual cortex, and have implications for rehabilitative strategies in human patients.
Maternal Dietary Intake of Omega-3 Fatty Acids Correlates Positively with Regional Brain Volumes in 1-Month-Old Term Infants
Authors: Morton Sarah U , Vyas Rutvi , Gagoski Borjan , Vu Catherine , Litt Jonathan , Larsen Ryan J , Kuchan Matthew J , Lasekan John B , Sutton Brad P , Grant P Ellen , Ou Yangming
Published: August 2019

Maternal nutrition is an important factor for infant neurodevelopment. However, prior magnetic resonance imaging (MRI) studies on maternal nutrients and infant brain have focused mostly on preterm infants or on few specific nutrients and few specific brain regions. We present a first study in term-born infants, comprehensively correlating 73 maternal nutrients with infant brain morphometry at the regional (61 regions) and voxel (over 300 000 voxel) levels. Both maternal nutrition intake diaries and infant MRI were collected at 1 month of life (0.9 ± 0.5 months) for 92 term-born infants (among them, 54 infants were purely breastfed and 19 were breastfed most of the time). Intake of nutrients was assessed via standardized food frequency questionnaire. No nutrient was significantly correlated with any of the volumes of the 61 autosegmented brain regions. However, increased volumes within subregions of the frontal cortex and corpus callosum at the voxel level were positively correlated with maternal intake of omega-3 fatty acids, retinol (vitamin A) and vitamin B12, both with and without correction for postmenstrual age and sex (P < 0.05, q < 0.05 after false discovery rate correction). Omega-3 fatty acids remained significantly correlated with infant brain volumes after subsetting to the 54 infants who were exclusively breastfed, but retinol and vitamin B12 did not. This provides an impetus for future larger studies to better characterize the effect size of dietary variation and correlation with neurodevelopmental outcomes, which can lead to improved nutritional guidance during pregnancy and lactation.
Environmental, Nutritional, and Socioeconomic Determinants of IBD Incidence: A Global Ecological Study
Authors: Piovani Daniele , Danese Silvio , Peyrin-Biroulet Laurent , Bonovas Stefanos
Published: August 2019

Background and Aims

The wide variation in inflammatory bowel disease [IBD] incidence across countries entails an opportunity to recognise global disease determinants and hypothesise preventive policies.

Methods

We fitted multivariable models to identify putative environmental, nutritional, and socioeconomic determinants associated with the incidence of IBD (i.e. ulcerative colitis [UC] and Crohn’s disease [CD]). We used the latest available country-specific incidence rates, and aggregate data for 20 determinants, from over 50 countries accounting for more than half of the global population. We presented the associations with exponentiated beta coefficients (exp[β]) indicating the relative increase of disease incidence per unit increase in the predictor variables.

Results

Country-specific incidence estimates demonstrate wide variability across the world, with a median of 4.8 new UC cases (interquartile range [IQR] 2.4–9.3), and 3.5 new CD cases [IQR 0.8–5.7] per 100 000 population per year. Latitude (exp[β] 1.05, 95% confidence interval [CI] 1.04‒1.06, per degree increase), prevalence of obesity [1.05, 1.02‒1.07, per 1% increase], and of tobacco smoking [0.97, 0.95‒0.99, per 1% increase] explained 71.5% of UC incidence variation across countries in the adjusted analysis. The model for CD included latitude [1.04, 1.02‒1.06], expenditure for health (1.03, 1.01‒1.05, per 100 purchasing power parity [PPP]/year per capita increase), and physical inactivity prevalence [1.03, 1.00‒1.06, per 1% increase], explaining 58.3% of incidence variation across countries. Besides expenditure for health, these associations were consistent in low/middle- and high-income countries.

Conclusions

Our analysis highlights factors able to explain a substantial portion of incidence variation across countries. Further high-quality research is warranted to develop global strategies for IBD prevention.
Deterioration of biventricular strain is an early marker of cardiac involvement in confirmed sarcoidosis
Authors: Kusunose Kenya , Fujiwara Mika , Yamada Hirotsugu , Nishio Susumu , Saijo Yoshihito , Yamada Nao , Hirata Yukina , Torii Yuta , Ise Takayuki , Yamaguchi Koji , Fukuda Daiju , Yagi Shusuke , Soeki Takeshi , Wakatsuki Tetsuzo , Sata Masataka
Published: August 2019

Aims 

Risk assessment of developing cardiac involvement in systemic sarcoidosis can be challenging because of limited data. Recently, attention has been given to left ventricular and right ventricular (LV and RV) involvement in cardiac sarcoidosis (CS) and its prevalence, relevance, and prognostic value. The aim of this study was to assess the role of biventricular strain to predict prognosis in confirmed sarcoidosis patients.

Methods and results 

LV and RV longitudinal strains (LSs) were evaluated by 2D speckle tracking in 139 consecutive confirmed sarcoidosis patients without other pre-existing structural heart diseases, and 52 age- and gender-matched control subjects. The primary endpoint was CS-related events (cardiac death or development of cardiac involvement). Sarcoidosis without cardiac involvement had significantly lower LV and RV free wall LS compared with control subjects. Basal LS had a higher area under the curve for differentiation of sarcoidosis in patients without cardiac involvement compared to control (cut-off value: −18% with 89% sensitivity and 69% specificity). During a median period of 50 months, the occurrence of CS-related events was observed in 20 patients. In a multivariate analysis, basal LV LS and RV free wall LS were associated with the events [hazard ratio (HR) 0.72, P < 0.001 and HR: 0.83, P = 0.006, respectively]. Patients with impaired biventricular function had significantly shorter event-free survival than those with preserved biventricular function (P < 0.001).

Conclusion 

Deterioration of biventricular strain was associated with CS-related events. This information might be useful for clinical evaluation and follow-up in sarcoidosis.
Long-term outcomes of chronic coronary syndrome worldwide: insights from the international CLARIFY registry
Authors: Sorbets Emmanuel , Fox Kim M , Elbez Yedid , Danchin Nicolas , Dorian Paul , Ferrari Roberto , Ford Ian , Greenlaw Nicola , Kalra Paul R , Parma Zofia , Shalnova Svetlana , Tardif Jean-Claude , Tendera Michal , Zamorano José Luis , Vidal-Petiot Emmanuelle , Steg Philippe Gabriel ,   CLARIFY investigators
Published: August 2019

Aims

Over the last decades, the profile of chronic coronary syndrome has changed substantially. We aimed to determine characteristics and management of patients with chronic coronary syndrome in the contemporary era, as well as outcomes and their determinants.

Methods and results

Data from 32 703 patients (45 countries) with chronic coronary syndrome enrolled in the prospective observational CLARIFY registry (November 2009 to June 2010) with a 5-year follow-up, were analysed. The primary outcome [cardiovascular death or non-fatal myocardial infarction (MI)] 5-year rate was 8.0% [95% confidence interval (CI) 7.7–8.3] overall [male 8.1% (7.8–8.5); female 7.6% (7.0–8.3)]. A cox proportional hazards model showed that the main independent predictors of the primary outcome were prior hospitalization for heart failure, current smoking, atrial fibrillation, living in Central/South America, prior MI, prior stroke, diabetes, current angina, and peripheral artery disease. There was an interaction between angina and prior MI (P = 0.0016); among patients with prior MI, angina was associated with a higher primary event rate [11.8% (95% CI 10.9–12.9) vs. 8.2% (95% CI 7.8–8.7) in patients with no angina, P < 0.001], whereas among patients without prior MI, event rates were similar for patients with [6.3% (95% CI 5.4–7.3)] or without angina [6.4% (95% CI 5.9–7.0)], P > 0.99. Prescription rates of evidence-based secondary prevention therapies were high.

Conclusion

This description of the spectrum of chronic coronary syndrome patients shows that, despite high rates of prescription of evidence-based therapies, patients with both angina and prior MI are an easily identifiable high-risk group who may deserve intensive treatment.

Clinical registry

ISRCTN43070564
Catheter ablation of ventricular arrhythmias and in-hospital mortality: insights from the German-wide Helios hospital network of 5052 cases
Authors: König Sebastian , Ueberham Laura , Müller-Röthing René , Wiedemann Michael , Ulbrich Michael , Sause Armin , Tebbenjohanns Jürgen , Schade Anja , Shin Dong-In , Staudt Alexander , Andrié René , Neuser Hans , Kuhlen Ralf , Arya Arash , Hindricks Gerhard , Bollmann Andreas
Published: August 2019

Aims

Catheter ablation (CA) of ventricular arrhythmias is one of the most challenging electrophysiological interventions with an increasing use over the last years. Several benefits must be weighed against the risk of potentially life-threatening complications which necessitates a steady reevaluation of safety endpoints. Therefore, the aims of this study were (i) to investigate overall in-hospital mortality in patients undergoing such procedures and (ii) to identify variables associated with in-hospital mortality in a German-wide hospital network.

Methods and results

Between January 2010 and September 2018, administrative data provided by 85 Helios hospitals were screened for patients with main or secondary discharge diagnosis of ventricular tachycardia (VT) or premature ventricular contractions (PVCs) in combination with an arrhythmia-related CA using ICD- and OPS codes. In 5052 cases (mean age 60.9 ± 14.3 years, 30.1% female) of 30 different hospitals, in-hospital mortality was 1.27% with a higher mortality in patients ablated for VT (1.99%, n = 2, 955) compared to PVC (0.24%, n = 2, 097, P < 0.01). Mortality rates were 2.06% in patients with ischaemic heart disease (IHD, n = 2, 137), 1.47% in patients with non-ischaemic structural heart disease (NIHD, n = 1, 224), and 0.12% in patients without structural heart disease (NSHD, n = 1, 691). Considering different types of hospital admission, mortality rates were 0.35% after elective (n = 2, 825), 1.60% after emergency admission/hospital transfer <24 h (n = 1, 314) and 3.72% following delayed hospital transfer >24 h after initial admission (n = 861, P < 0.01 vs. elective admission and emergency admission/hospital transfer <24 h). In multivariable analysis, a delayed hospital transfer >24 h [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.59–3.28, P < 0.01], the occurrence of procedure-related major adverse events (OR 6.81, 95% CI 2.90–16.0, P < 0.01), Charlson Comorbidity Index (CCI, OR 2.39, 95% CI 1.56–3.66, P < 0.01) and its components congestive heart failure (OR 8.04, 95% CI 1.71–37.8, P < 0.01), and diabetes mellitus (OR 1.59, 95% CI 1.13–2.22, P < 0.01) were significantly associated with in-hospital death.

Conclusions

We reported in-hospital mortality rates after CA of ventricular arrhythmias in the largest multicentre, administrative dataset in Germany which can be implemented in quality management programs. Aside from comorbidities, a delayed hospital transfer to a CA performing centre is associated with an increased in-hospital mortality. This deserves further studies to determine the optimal management strategy.
Who do we discharge from renal clinic and what does it mean for primary care?
Authors: Pyart Rhodri , Lim Sheryl , Hussein Bilal , Riley Steve , Roberts Gareth
Published: August 2019

Background

It is unclear whether discharging patients from renal clinic to primary care is safe.

Aim

To determine the characteristics, primary care monitoring and renal outcomes of patients discharged from renal clinic.

Design and setting

A retrospective study of 2236 adults discharged from a tertiary renal clinic between 2013–2018.

Method

Patient demographics, primary renal disease, laboratory results and timeline dates were collected from the renal IT system. Timing of blood tests, renal progression, needing dialysis and patient survival were analysed. Reasons for discharge and cause of disease progression were reviewed in patients developing new estimated glomerular filtration rate <20 ml/min/1.73 m2.

Results

Patients were older (median age 75; interquartile range 63–84) with non-progressive, seemingly non-proteinuric renal disease. Median time to repeat blood test post-discharge was 75 days with 90% tested within 12 months. Sixty-six percent saw an improvement in kidney function post-discharge and only 13% had a decline of >10 ml/min/1.73 m2. Only 132 patients (6%) developed new advanced chronic kidney disease (estimated glomerular filtration rate < 20 ml/min/1.73 m2) of whom 40% were palliative, 36% had developed acute kidney injury and 23% discharged for failing to attend clinic. One hundred and thirty-four patients (6%) were referred back to nephrology and eight started dialysis of whom six were discharged for failure to attend clinic.

Conclusion

Most discharged patients are low risk of progressive renal disease and need infrequent monitoring. Non-adherent patients discharged for failing to attend appear to be at risk of poor outcomes and new strategies are needed to better support this population.
Deletion of JEN1 and ADY2 reduces lactic acid yield from an engineered Saccharomyces cerevisiae, in xylose medium, expressing a heterologous lactate dehydrogenase
Authors: Turner Timothy L , Lane Stephan , Jayakody Lahiru N , Zhang Guo-Chang , Kim Heejin , Cho Whiyeon , Jin Yong-Su
Published: August 2019

Microorganisms have evolved to produce specific end products for many reasons, including maintaining redox balance between NAD+ and NADH. The yeast Saccharomyces cerevisiae, for example, produces ethanol as a primary end product from glucose for the regeneration of NAD+. Engineered S. cerevisiae strains have been developed to ferment lignocellulosic sugars, such as xylose, to produce lactic acid by expression of a heterologous lactate dehydrogenase (ldhA from Rhizopus oryzae) without genetic perturbation to the native ethanol pathway. Surprisingly, the engineered yeast strains predominantly produce ethanol from glucose, but produce lactic acid as the major product from xylose. Here, we provide initial evidence that the shift in product formation from ethanol to lactic acid during xylose fermentation is at least partially dependent on the presence of functioning monocarboxylate transporter genes/proteins, including JEN1 and ADY2, which are downregulated and unstable in the presence of glucose, but upregulated/stable on xylose. Future yeast metabolic engineering studies may find the feedstock/carbon selection, such as xylose, an important step toward improving the yield of target end products.
Older Adults' Perceptions of Sedentary Behavior: A Systematic Review and Thematic Synthesis of Qualitative Studies
Authors: Compernolle Sofie , De Cocker Katrien , Cardon Greet , De Bourdeaudhuij Ilse , Van Dyck Delfien
Published: August 2019

Background and Objectives

Reducing sedentary behavior contributes to healthy aging. In order to develop sedentary behavior interventions, insight is needed into older adults' perceptions of (reducing) sedentary behavior. Therefore, this systematic review aims to synthesize qualitative evidence of older adults' perceptions towards (a) the concept of sedentary behavior, (b) barriers and facilitators of sedentary behavior, and (c) solutions and strategies to reduce sedentary behavior.

Research Design and Methods

A systematic search was conducted in four electronic databases. Inclusion criteria comprised qualitative and mixed-methods studies investigating the perceptions of older adults (mean age: ≥60 years) towards (reducing) sedentary behavior. Quality of the included studies was rated using the Critical Appraisal Skills Programme (CASP) Qualitative Checklist. Relevant data on older adults' perceptions were extracted and imported into NVivo. Two independent reviewers analyzed the data by means of thematic synthesis (line-by-line coding, constructing descriptive (sub)themes, developing analytical themes).

Results

Fifteen studies were included. Four analytical themes were developed to be considered when aiming to reduce sedentary behavior in older adults: the lack of knowledge on/awareness of sedentary behavior, the habitual nature of sedentary behavior, the importance of enjoyment and convenience, and the key role of aging.

Discussion and Implications

The reduction of older adults' sedentary behavior will likely be challenging as sedentary behavior seems to be firmly incorporated into older adults' daily routines, and strongly linked with positive reinforcement. Both aspects deserve thoughtful attention by intervention developers and health care professionals who aim to promote healthy aging by reducing sedentary behavior.
Aortic root remodelling with external ring annuloplasty in acute type A aortic dissection
Authors: Kato Yasuyuki , Sasaki Kenichi , Yamauchi Hidetaka , Kanno Yasuyuki , Jinno Taiyo , Yamada Muneaki , Kiyama Hiroshi , Koyanagi Toshiya
Published: August 2019

OBJECTIVES

To investigate the early and mid-term results of aortic root remodelling with external ring annuloplasty in acute type A aortic dissection.

METHODS

From January 2015 to April 2019, a total of 194 patients underwent emergency or urgent operation for acute type A aortic dissection in our hospital. Of these, outcomes in 18 patients who underwent valve-sparing aortic root remodelling with external ring annuloplasty were retrospectively evaluated.

RESULTS

The mean age of the 18 patients was 49 ± 14 years. Fourteen patients (78%) were men. Five patients had Marfan syndrome and 2 patients had bicuspid aortic valve. Two patients had coronary malperfusion and 1 patient had cerebral malperfusion. All 18 patients underwent aortic root remodelling with external ring annuloplasty. Cusp repair using central cusp plication was required in 9 patients. Concomitant procedures were hemiarch replacement in 8 patients, total arch replacement in 7 patients, partial arch replacement in 1 patient and coronary artery bypass grafting to the right coronary artery in 3 patients. Thirty-day mortality rate was 5.6% (1 of 18). Postoperative echocardiography showed aortic regurgitation of <1+ in all patients. During follow-up (mean 56 ± 41 months), 1 case of recurrent aortic regurgitation required aortic valve replacement.

CONCLUSIONS

Aortic root remodelling with external ring annuloplasty may be an appropriate treatment in middle-aged or younger patients presenting with acute type A aortic dissection.
(R)-Ketamine Rapidly Ameliorates the Decreased Spine Density in the Medial Prefrontal Cortex and Hippocampus of Susceptible Mice After Chronic Social Defeat Stress
Authors: Zhang Jiancheng , Qu Youge , Chang Lijia , Pu Yaoyu , Hashimoto Kenji
Published: August 2019

Background

A recent study demonstrated that spine formation rates by ketamine in the prefrontal cortex (PFC) were not altered at 3–6 h following a single injection, but were markedly altered at 12–24 h. Here, we investigated the acute (3 h post-treatment) effects of (R)-ketamine in the decreased spine density in the medial PFC (mPFC) and hippocampus in susceptible mice after chronic social defeat stress (CSDS).

Methods

(R)-ketamine (10 mg/kg) or saline was administered intraperitoneally to CSDS-susceptible mice. Dendritic spine density in the mPFC and hippocampus was measured 3 h after a single injection.

Results

(R)-ketamine significantly ameliorated the decreased spine density in the prelimbic area of mPFC, Cornu Ammonis3, and dentate gyrus of the hippocampus of CSDS-susceptible mice

Conclusions

This study suggests that (R)-ketamine rapidly ameliorates the decreased spine density in the mPFC and hippocampus of CSDS-susceptible mice, resulting in its rapid-acting antidepressant effects.
Lessons for test and treat in an antiretroviral programme after decentralisation in Uganda: a retrospective analysis of outcomes in public healthcare facilities within the Lablite project
Authors: Kiwuwa-Muyingo S , Abongomera G , Mambule I , Senjovu D , Katabira E , Kityo C , Gibb D M , Ford D , Seeley J
Published: August 2019

Background

We describe the decentralisation of antiretroviral therapy (ART) alongside Option B+ roll-out in public healthcare facilities in the Lablite project in Uganda. Lessons learned will inform programmes now implementing universal test and treat (UTT).

Methods

Routine data were retrospectively extracted from ART registers between October 2012 and March 2015 for all adults and children initiating ART at two primary care facilities (spokes) and their corresponding district hospitals (hubs) in northern and central Uganda. We describe ART initiation over time and retention and use of Cox models to explore risk factors for attrition due to mortality and loss to follow-up. Results from tracing of patients lost to follow-up were used to correct retention estimates.

Results

Of 2100 ART initiations, 1125 were in the north, including 944 (84%) at the hub and 181 (16%) at the spokes; children comprised 95 (10%) initiations at the hubs and 14 (8%) at the spokes. Corresponding numbers were 642 (66%) at the hub and 333 (34%) at the spokes in the central region (77 [12%] and 22 [7%], respectively, in children). Children <3 y of age comprised the minority of initiations in children at all sites. Twenty-three percent of adult ART initiations at the north hub were Option B+ compared with 45% at the spokes (25% and 65%, respectively, in the central region). Proportions retained in care in the north hub at 6 and 12 mo were 92% (95% CI 90 to 93) and 89% (895% CI 7 to 91), respectively. Corresponding corrected estimates in the north spokes were 87% (95% CI 78 to 93) and 82% (95% CI 72 to 89), respectively. In the central hub, corrected estimates were 84% (95% CI 80 to 87) and 78% (95% CI 74 to 82), and were 89% (95% CI 77.9 to 95.1) and 83% (95% CI 64.1 to 92.9) at the spokes, respectively. Among adults newly initiating ART, being older was independently associated with a lower risk of attrition (adjusted hazard ratio [aHR] 0.93 per 5 y [95% CI 0.88 to 0.97]). Other independent risk factors included initiating with a tenofovir-based regimen vs zidovudine (aHR 0.60 [95% CI 0.46 to 0.77]), year of ART initiation (2013 aHR 1.55 [95% CI 1.21 to 1.97], ≥2014 aHR 1.41 [95% CI 1.06 to 1.87]) vs 2012, hub vs spoke (aHR 0.35 [95% CI 0.29 to 0.43]) and central vs north (aHR 2.28 [95% CI 1.86 to 2.81]). Independently, patient type was associated with retention.

Conclusions

After ART decentralisation, people living with human immunodeficiency virus (HIV) were willing to initiate ART in rural primary care facilities. Retention on ART was variable across facilities and attrition was higher among some groups, including younger adults and women initiating ART during pregnancy/breastfeeding. Interventions to support these groups are required to optimise benefits of expanded access to HIV services under UTT.
A Growing Queer Divide: The Divergence between Transnational Advocacy Networks and Foreign Aid in Diffusing LGBT Policies
Authors: Velasco Kristopher
Published: August 2019

Despite years of success, lesbian, gay, bisexual, and transgender (LGBT) norms are becoming increasingly polarized across the global landscape—with some countries strongly complying with new expectations while others openly defy them. To explain these divergent paths, I investigate the transmission of global LGBT norms via two mechanisms: transnational advocacy networks and foreign aid conditionalities. In examining LGBT policy adoption across 110 non-Organisation for Economic Co-operation and Development (OECD) countries between 1990 and 2016, I find evidence that the process through which states are exposed to LGBT norms can indeed help explain these different approaches. Exposure to LGBT norms through transnational advocacy networks enhances the effect of these norms and is associated with more progressive policy adoption, while greater dependence on foreign aid pushes states to reject LGBT norms. Consequently, this study provides new insights into how the mechanism through which countries are exposed to norms shapes compliance and adds new evidence questioning the effectiveness of foreign aid as a tool to advance LGBT rights.
Cephalosporin nitric oxide-donor prodrug DEA-C3D disperses biofilms formed by clinical cystic fibrosis isolates of Pseudomonas aeruginosa
Authors: Soren Odel , Rineh Ardeshir , Silva Diogo G , Cai Yuming , Howlin Robert P , Allan Raymond N , Feelisch Martin , Davies Jane C , Connett Gary J , Faust Saul N , Kelso Michael J , Webb Jeremy S
Published: August 2019

Objectives

The cephalosporin nitric oxide (NO)-donor prodrug DEA-C3D (‘DiEthylAmin-Cephalosporin-3′-Diazeniumdiolate’) has been shown to initiate the dispersal of biofilms formed by the Pseudomonas aeruginosa laboratory strain PAO1. In this study, we investigated whether DEA-C3D disperses biofilms formed by clinical cystic fibrosis (CF) isolates of P. aeruginosa and its effect in combination with two antipseudomonal antibiotics, tobramycin and colistin, in vitro.

Methods

β-Lactamase-triggered release of NO from DEA-C3D was confirmed using a gas-phase chemiluminescence detector. MICs for P. aeruginosa clinical isolates were determined using the broth microdilution method. A crystal violet staining technique and confocal laser scanning microscopy were used to evaluate the effects of DEA-C3D on P. aeruginosa biofilms alone and in combination with tobramycin and colistin.

Results

DEA-C3D was confirmed to selectively release NO in response to contact with bacterial β-lactamase. Despite lacking direct, cephalosporin/β-lactam-based antibacterial activity, DEA-C3D was able to disperse biofilms formed by three P. aeruginosa clinical isolates. Confocal microscopy revealed that DEA-C3D in combination with tobramycin produces similar reductions in biofilm to DEA-C3D alone, whereas the combination with colistin causes near complete eradication of P. aeruginosa biofilms in vitro.

Conclusions

DEA-C3D is effective in dispersing biofilms formed by multiple clinical isolates of P. aeruginosa and could hold promise as a new adjunctive therapy to patients with CF.
Is the subcutaneous route an alternative for administering ertapenem to older patients? PHACINERTA study
Authors: Roubaud Baudron Claire , Legeron Rachel , Ollivier Julien , Bonnet Fabrice , Greib Carine , Guerville Florent , Cazanave Charles , Kobeh David , Cressot Véronique , Moneger Nicolas , Videau Marie-Neige , Thiel Elise , Foucaud Carine , Lafargue Aurélie , de Thezy Albane , Durrieu Jessica , Bourdel Marchasson Isabelle , Pinganaud Geneviève , Breilh Dominique
Published: August 2019

Background

Antibiotic administration by subcutaneous (SC) injection is common practice in French geriatric wards as an alternative to the intravenous (IV) route, but few pharmacokinetic/pharmacodynamic data are available. Ertapenem is useful for the treatment of infections with ESBL-producing enterobacteria.

Objectives

To report and compare ertapenem pharmacokinetic data between IV and SC routes in older persons.

Methods

Patients >65 years of age receiving ertapenem (1 g once daily) for at least 48 h (IV or SC, steady-state) were prospectively enrolled. Total ertapenem concentrations [residual (C0), IV peak (C0.5) and SC peak (C2.5)] were determined by UV HPLC. Individual-predicted AUC0–24 values were calculated and population pharmacokinetic analyses were performed. Using the final model, a Monte Carlo simulation involving 10 000 patients evaluated the influence of SC or IV administration on the PTA. Tolerance to ertapenem and recovery were also monitored. ClinicalTrials.gov identifier: NCT02505386.

Results

Ten (mean ± SD age=87±7 years) and 16 (age=88±5 years) patients were included in the IV and SC groups, respectively. The mean C0 and C2.5 values were not significantly different between the IV and SC groups (C0=12±5.9 versus 12±7.4 mg/L, P=0.97; C2.5=97±42 versus 67±41 mg/L, P=0.99). The mean C0.5 was higher in the IV group compared with the SC group (C0.5=184±90 versus 51±66 mg/L, P=0.001). The mean individual AUCs (1126.92±334.99 mg·h/L for IV versus 1005.3±266.0 mg·h/L for SC, P=0.38) and PTAs were not significantly different between groups. No severe antibiotic-related adverse effects were noted.

Conclusions

SC administration of ertapenem is an alternative to IV administration in older patients.
Leaf: an open-source, model-agnostic, data-driven web application for cohort discovery and translational biomedical research
Authors: Dobbins Nicholas J , Spital Clifford H , Black Robert A , Morrison Jason M , de Veer Bas , Zampino Elizabeth , Harrington Robert D , Britt Bethene D , Stephens Kari A , Wilcox Adam B , Tarczy-Hornoch Peter , Mooney Sean D
Published: August 2019

Objective

Academic medical centers and health systems are increasingly challenged with supporting appropriate secondary use of clinical data. Enterprise data warehouses have emerged as central resources for these data, but often require an informatician to extract meaningful information, limiting direct access by end users. To overcome this challenge, we have developed Leaf, a lightweight self-service web application for querying clinical data from heterogeneous data models and sources.

Materials and Methods

Leaf utilizes a flexible biomedical concept system to define hierarchical concepts and ontologies. Each Leaf concept contains both textual representations and SQL query building blocks, exposed by a simple drag-and-drop user interface. Leaf generates abstract syntax trees which are compiled into dynamic SQL queries.

Results

Leaf is a successful production-supported tool at the University of Washington, which hosts a central Leaf instance querying an enterprise data warehouse with over 300 active users. Through the support of UW Medicine (https://uwmedicine.org), the Institute of Translational Health Sciences (https://www.iths.org), and the National Center for Data to Health (https://ctsa.ncats.nih.gov/cd2h/), Leaf source code has been released into the public domain at https://github.com/uwrit/leaf.

Discussion

Leaf allows the querying of single or multiple clinical databases simultaneously, even those of different data models. This enables fast installation without costly extraction or duplication.

Conclusions

Leaf differs from existing cohort discovery tools because it does not specify a required data model and is designed to seamlessly leverage existing user authentication systems and clinical databases in situ. We believe Leaf to be useful for health system analytics, clinical research data warehouses, precision medicine biobanks, and clinical studies involving large patient cohorts.
The Epidemiology of Burns in Children in Guatemala: A Single Center Report
Authors: Santiso Lourdes , Tapking Christian , Lee Jong O , Zapata-Sirvent Ramon , Pittelli Christine A , Suman Oscar E
Published: August 2019

Children in low- to middle-income countries are at high risk for sustaining severe burns. This study aimed to analyze the characteristics of pediatric burns in Guatemala that could help identify risk factors and guide prevention efforts. A retrospective review of the characteristics of patients < 18 years of age that were burned in Guatemala between 2015 and 2018 and treated at the Hospital Roosevelt Burn Unit in Guatemala City was performed. The medical records of 949 patients were reviewed (year 2015: 224, year 2016: 238, year 2017: 251, year 2018: 236). Mean age of the patients was 4.0 ± 3.6 years. Majority of the patients were male (54.2%) and suffered from scald burns (68.5%) due to spilling or falling into hot water. Children under the age of 9 years predominantly suffered from scald burns, whereas older children more frequently sustained flame burns. The mortality rate over the 4-year period was 5.2%. As in other low-income countries, pediatric burns in Guatemala are frequent and usually due to scald. Demographic characteristics have to be taken into account when developing strategies for improvements of prevention and treatment or transferring these from high-income countries. Especially education of parents and safety of daily tasks are crucial. Special attention and focusing of efforts in areas of higher incidence should be sought.
Exchange rate effects on cross-border commuting: evidence from the Swiss–Italian border
Authors: Bello Piera
Published: August 2019

Are cross-border workers responsive to changes in the exchange rate between the home and host countries’ currencies? I answer this question by examining the effects of the appreciation of the Swiss franc (CHF) relative to the euro (EUR) on labour supply decisions of Italian cross-border workers. I use hourly data on traffic flows in Ticino, the southernmost canton of Switzerland, together with three additional datasets (the Cross-border Commuter Statistics, the Swiss Earnings Structure Survey, and Google trend data). The results show that a 10% appreciation in the CHF increases the number of cars along the Swiss–Italian border by 1.6–2.7% more than in the rest of the canton. This effect is found only during specific time intervals, which differ according to the direction of traffic flow; specifically, from Italy to Switzerland in early morning, from Switzerland to Italy in the afternoon, and in both directions in late morning. Moreover, when the CHF is stronger, more people from Italy look for jobs in Ticino, and the number of cross-border workers increases in municipalities within a driving distance of up to 10 km from the border. Finally, additional evidence suggests that cross-border workers also react to the appreciation by increasing their number of hours worked.
Roundwood Use by Southern Wood Pellet Mills: Findings from Timber Product Output Mill Surveys
Authors: Brandeis Consuelo , Abt Karen Lee
Published: August 2019

Between 2012 and 2017, southern wood pellet exports grew by approximately 180 percent, whereas the regions’ wood pellet mill capacity increased from 3.8 to 7.7 million tons over the same period. This capacity and production growth generates concerns regarding impacts on resource sustainability and to traditional forest industries that use feedstocks similar to those used by pellet mills. Information on wood pellet producers’ patterns and levels of roundwood consumption can help evaluate the potential impacts of the industry on the forest resource. We use mill-level data collected by the USDA Forest Service Southern Research Station Forest Inventory and Analysis program to help characterize activity by southern wood pellet mills that consume roundwood. Our analysis shows that the volume of roundwood used for pellet production has increased, representing close to 2 percent of all southern timber products output and 27 percent of all industrial fuelwood output (excluding firewood) during 2015.
Magnetized hybrid stars: effects of slow and rapid phase transitions at the quark–hadron interface
Authors: Mariani Mauro , Orsaria Milva G , Ranea-Sandoval Ignacio F , Lugones Germán
Published: August 2019

We study the influence of strong magnetic fields in hybrid stars, composed by hadrons and a pure quark matter core, and analyse their structure and stability as well as some possible evolution channels due to the magnetic field decay. Using an ad hoc parametrization of the magnetic field strength and taking into account Landau-quantization effects in matter, we calculate hybrid magnetized equations of state and some associated quantities, such as particle abundances and matter magnetization, for different sets of parameters and different magnetic field strengths. Moreover, we compute the magnetized stable stellar configurations, the mass versus radius and the gravitational mass versus central energy density relationships, the gravitational mass versus baryon mass diagram, and the tidal deformability. Our results are in agreement with both, the $\sim 2\, \mathrm{M}_\odot$ pulsars and the data obtained from GW170817. In addition, we study the stability of stellar configurations assuming that slow and rapid phase transitions occur at the sharp hadron–quark interface. We find that, unlike in the rapid transition scenario, where ∂M/∂ϵc < 0 is a sufficient condition for instability, in the slow transition scenario there exists a connected extended stable branch beyond the maximum mass star, for which ∂M/∂ϵc < 0. Finally, analysing the gravitational mass versus baryon mass relationship, we have calculated the energy released in transitions between stable stellar configurations. We find that the inclusion of the magnetic field and the existence of new stable branches allows the possibility of new channels of transitions that fulfil the energy requirements to explain gamma-ray bursts.
A magnetic white dwarf with five H α components
Authors: Kilic Mukremin , Rolland B , Bergeron P , Vanderbosch Z , Benni P , Garlitz J
Published: August 2019

G183−35 is an unusual white dwarf that shows an H α line split into five components, instead of the usual three components seen in strongly magnetic white dwarfs. Potential explanations for the unusual set of lines include a double degenerate system containing two magnetic white dwarfs and/or rotational modulation of a complex magnetic field structure. Here, we present time-resolved spectroscopy of G183−35 obtained at the Gemini Observatory. These data reveal two sets of absorption lines that appear and disappear over a period of about 4 h. We also detect low-level (0.2 per cent) variability in optical photometry at the same period. We demonstrate that the spectroscopic and photometric variability can be explained by the presence of spots on the surface of the white dwarf and a change in the average field strength from about 4.6 to 6.2 MG. The observed variability is clearly due to G183−35’s relatively short spin period. However, rotational modulation of a complex magnetic field by itself cannot explain the changes seen in the central H α component. An additional source of variability in the line profiles, most likely due to a chemically inhomogeneous surface composition, is also needed. We propose further observations of similar objects to test this scenario.
Disappearance of Icelandic Walruses Coincided with Norse Settlement
Authors: Keighley Xénia , Pálsson Snæbjörn , Einarsson Bjarni F , Petersen Aevar , Fernández-Coll Meritxell , Jordan Peter , Olsen Morten Tange , Malmquist Hilmar J
Published: August 2019

There is a growing body of evidence demonstrating the impacts of human arrival in new “pristine” environments, including terrestrial habitat alterations and species extinctions. However, the effects of marine resource utilization prior to industrialized whaling, sealing, and fishing have largely remained understudied. The expansion of the Norse across the North Atlantic offers a rare opportunity to study the effects of human arrival and early exploitation of marine resources. Today, there is no local population of walruses on Iceland, however, skeletal remains, place names, and written sources suggest that walruses existed, and were hunted by the Norse during the Settlement and Commonwealth periods (870–1262 AD). This study investigates the timing, geographic distribution, and genetic identity of walruses in Iceland by combining historical information, place names, radiocarbon dating, and genomic analyses. The results support a genetically distinct, local population of walruses that went extinct shortly after Norse settlement. The high value of walrus products such as ivory on international markets likely led to intense hunting pressure, which—potentially exacerbated by a warming climate and volcanism—resulted in the extinction of walrus on Iceland. We show that commercial hunting, economic incentives, and trade networks as early as the Viking Age were of sufficient scale and intensity to result in significant, irreversible ecological impacts on the marine environment. This is to one of the earliest examples of local extinction of a marine species following human arrival, during the very beginning of commercial marine exploitation.
Ancient Mitochondrial Gene Transfer between Fungi and the Orchids
Authors: Sinn Brandon T , Barrett Craig F
Published: August 2019

The mitochondrial genomes (mitogenomes) of plants are known to incorporate and accumulate DNA from intra- and extracellular donors. Despite the intimate relationships formed between flowing plants (angiosperms) and fungi, lengthy fungal-like sequence has not been identified in angiosperm mitogenomes to date. Here, we present multiple lines of evidence documenting horizontal gene transfer (HGT) between the mitogenomes of fungi and the ancestors of the orchids, plants that are obligate parasites of fungi during their early development. We show that the ancestor of the orchids acquired an ∼270-bp fungal mitogenomic region containing three transfer RNA genes. We propose that the short HGT was later replaced by a second HGT event transferring >8 kb and 14 genes from a fungal mitogenome to that of the ancestor of the largest orchid subfamily, Epidendroideae. Our results represent the first evidence of genomic-scale HGT between fungal and angiosperm mitogenomes and demonstrate that the length intergenic spacer regions of angiosperm mitogenomes can effectively fossilize the genomic remains of ancient, nonplant organisms.