bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting the structure of turtle assemblages along a megatransect in West Africa
Authors: Luiselli Luca , Akani Godfrey C , Ajong Stephanie N , George Adedolapo , Di Vittorio Massimiliano , Eniang Edem A , Dendi Daniele , Hema Emmanuel M , Petrozzi Fabio , Fa John E
Published: March 2020

Understanding large- and small-scale patterns and the determinants of species richness is central for the study of evolutionary mechanisms. The extent to which species richness in local communities is related to larger-scale processes is a pre-eminent topic in ecological and evolutionary research. To investigate how local and regional species richness are related, we sampled freshwater turtle assemblages in seven localities to represent the variation in ecological conditions along a 90 km south–north megatransect in Benin, West Africa. In each locality, all turtles captured were identified and measured, and the microhabitat in which individual turtles were observed was classified. Based on these data, we used community diversity metrics to compare turtle assemblages. Spatial autocorrelation did not affect our data. For all localities pooled, two species (Pelusios castaneus and Pelomedusa olivacea) were the most common and one species (Trionyx triunguis) was the rarest. Analyses of the commonest and more numerous species showed that the abundance of Pelusios castaneus declined with an increase in latitude and longitude, but the opposite was true for Pelomedusa olivacea. We showed that various characteristics of the microhabitat were significantly correlated with the abundance of the two common species. We found significant but variable south–north gradients in microhabitat use for different turtle species. Our results highlight the importance of studying interactions between local environments, the ecological requirements of each species and their synecological relationships.
Effects of Olfactory Stimulation on Past and Future Thinking in Alzheimer’s Disease
Authors: Glachet Ophélie , El Haj Mohamad
Published: March 2020

Several studies have demonstrated that Alzheimer’s disease (AD) is associated not only with difficulty in remembering past events but also with a compromised ability to imagine future ones. Recent empirical research has also demonstrated that odor is an effective cue to alleviate difficulty in remembering past events in AD. We investigated whether odor exposure would help AD patients to imagine future events. To this end, we invited AD patients and control participants to evoke past and future events after odor exposure or without odor. Analysis showed that AD patients and control participants produced more specific and more emotional past and future events after odor exposure than without odor. However, odor exposure did not improve the retrieval time for future thinking in AD participants. This study is the first to demonstrate positive effects of odor exposure on the ability of AD patients to project themselves into the future.
Invasive Aspergillosis Due to Aspergillus Section Usti: A Multicenter Retrospective Study
Authors: Glampedakis Emmanouil , Cassaing Sophie , Fekkar Arnaud , Dannaoui Eric , Bougnoux Marie-Elisabeth , Bretagne Stéphane , Neofytos Dionysios , Schreiber Peter W , Hennequin Christophe , Morio Florent , Shadrivova Olga , Bongomin Felix , Fernández-Ruiz Mario , Bellanger Anne Pauline , Arikan-Akdagli Sevtap , Erard Veronique , Aigner Maria , Paolucci Michela , Khanna Nina , Charpentier Eléna , Bonnal Christine , Brun Sophie , Gabriel Frederic , Riat Arnaud , Zbinden Reinhard , Le Pape Patrice , Klimko Nikolai , Lewis Russel E , Richardson Malcolm , İnkaya Ahmet Cagkan , Coste Alix T , Bochud Pierre-Yves , Lamoth Frederic
Published: March 2020

Background

Aspergillus spp. of section Usti (A. ustus) represent a rare cause of invasive aspergillosis (IA). This multicenter study describes the epidemiology and outcome of A. ustus infections.

Methods

Patients with A. ustus isolated from any clinical specimen were retrospectively identified in 22 hospitals from 8 countries. When available, isolates were sent for species identification (BenA/CaM sequencing) and antifungal susceptibility testing. Additional cases were identified by review of the literature. Cases were classified as proven/probable IA or no infection, according to standard international criteria.

Results

Clinical report forms were obtained for 90 patients, of whom 27 had proven/probable IA. An additional 45 cases were identified from literature review for a total of 72 cases of proven/probable IA. Hematopoietic cell and solid-organ transplant recipients accounted for 47% and 33% cases, respectively. Only 8% patients were neutropenic at time of diagnosis. Ongoing antimold prophylaxis was present in 47% of cases. Pulmonary IA represented 67% of cases. Primary or secondary extrapulmonary sites of infection were observed in 46% of cases, with skin being affected in 28% of cases. Multiple antifungal drugs were used (consecutively or in combination) in 67% of cases. The 24-week mortality rate was 58%. A. calidoustus was the most frequent causal agent. Minimal inhibitory concentrations encompassing 90% isolates (MIC90) were 1, 8, >16, and 4 µg/mL for amphotericin B, voriconazole, posaconazole, and isavuconazole, respectively.

Conclusions

Aspergillus ustus IA mainly occurred in nonneutropenic transplant patients and was frequently associated with extrapulmonary sites of infection. Mortality rate was high and optimal antifungal therapy remains to be defined.
Strongyloides stercoralisInfection in Solid Organ Transplant Patients Is Associated With Eosinophil Activation and Intestinal Inflammation: A Cross-sectional Study
Authors: Clark Eva , Pritchard Haley , Hemmige Vagish , Restrepo Alejandro , Bautista Karla , Damania Ashish , Ricciardi Alessandra , Nutman Thomas B , Mejia Rojelio
Published: March 2020

Background

Strongyloidiasis can cause devastating morbidity and death in immunosuppressed patients. Identification of reliable biomarkers for strongyloidiasis in immunosuppressed patients is critical for the prevention of severe disease.

Methods

In this cross-sectional study of solid organ transplant (SOT) candidates and recipients, we quantified Strongyloides-specific IgG to the recombinant NIE-Strongyloides antigen and/or to a soluble extract of S. stercoralis somatic antigens (“crude antigen”) using enzyme-linked immunosorbent assays (ELISAs). We also measured peripheral eosinophilia, 4 different eosinophil granule proteins, and intestinal fatty acid–binding protein (IFABP).

Results

We evaluated serum biomarkers in 149 individuals; 77 (52%) pre-SOT and 72 (48%) post-SOT. Four percent (6/149) tested positive by NIE ELISA and 9.6% (11/114) by crude antigen ELISA (overall seropositivity of 9.4% [14/149]). Seropositive patients had higher absolute eosinophil counts (AECs) than seronegative patients (P = .004). AEC was positively correlated to the levels of eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) (P < .05), while IFABP was positively related to the 2 other eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]; Spearman’s r = 0.3090 and 0.3778, respectively; P < .05; multivariate analyses slopes = 0.70 and 2.83, respectively).

Conclusions

This study suggests that, in SOT patients, strongyloidiasis triggers both eosinophilia and eosinophil activation, the latter being associated with intestinal inflammation. These data provide insight into the pathogenesis of S. stercoralis infection in the immunocompromised population at high risk of severe strongyloidiasis syndromes.
Global Action for Local Impact: The 11th International Conference on Typhoid and Other Invasive Salmonelloses
Authors: Duff Noah , Steele A Duncan , Garrett Denise
Published: March 2020

Typhoid and other invasive salmonelloses continue to cause an estimated 14.8 million cases and > 200 000 deaths annually, largely affecting children in low- and middle-income countries. However, recent strides in global policy have paved the way for accelerated progress with prevention and control efforts. To translate these recent advancements at the global level into real impact in communities at the local level, the Coalition against Typhoid, based at the Sabin Vaccine Institute, convened the 11th International Conference on Typhoid and Other Invasive Salmonelloses in Hanoi, Vietnam, in March 2019. Here, we review the significant topics and research discussed at the conference, including diagnostics, environmental surveillance, drug resistance, burden of disease, and vaccines, as well as additional prevention and control interventions.
Analysis of Epidemiological and Clinical Features in Older Patients With Coronavirus Disease 2019 (COVID-19) Outside Wuhan
Authors: Lian Jiangshan , Jin Xi , Hao Shaorui , Cai Huan , Zhang Shanyan , Zheng Lin , Jia Hongyu , Hu Jianhua , Gao Jianguo , Zhang Yimin , Zhang Xiaoli , Yu Guodong , Wang Xiaoyan , Gu Jueqing , Ye Chanyuan , Jin Ciliang , Lu Yingfeng , Yu Xia , Yu Xiaopeng , Ren Yue , Qiu Yunqing , Li Lanjuan , Sheng Jifang , Yang Yida
Published: March 2020

Background

The outbreak of coronavirus disease 2019 (COVID-19) has become a large threat to public health in China, with high contagious capacity and varied mortality. This study aimed to investigate the epidemiological and clinical characteristics of older patients with COVID-19 outside Wuhan.

Methods

A retrospective study was performed, with collecting data from medical records of confirmed COVID-19 patients in Zhejiang province from 17 January to 12 February 2020. Epidemiological, clinical, and treatment data were analyzed between older (≥ 60 years) and younger (< 60 years) patients.

Results

A total of 788 patients with confirmed COVID-19 were selected; 136 were older patients with corresponding mean age of 68.28 ± 7.31 years. There was a significantly higher frequency of women in older patient group compared with younger patients (57.35% vs 46.47%, P = .021). The presence of coexisting medical conditions was significantly higher in older patients compared with younger patients (55.15% vs 21.93%, P < .001), including the rate of hypertension, diabetes, heart disease, and chronic obstructive pulmonary disease. Significantly higher rates of severe clinical type (older vs younger groups: 16.18% vs 5.98%, P < .001), critical clinical type (8.82% vs 0.77%, P < .001), shortness of breath (12.50% vs 3.07%, P < .001), and temperature of > 39.0°C (13.97% vs 7.21%, P = .010) were observed in older patients compared with younger patients. Finally, higher rates of intensive care unit admission (9.56% vs 1.38%, P < .001) and methylprednisolone application (28.68% vs 9.36%, P < .001) were also identified in older patients compared with younger ones.

Conclusions

The specific epidemiological and clinical features of older COVID-19 patients included significantly higher female sex, body temperature, comorbidities, and rate of severe and critical type disease.
Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China
Authors: Qin Chuan , Zhou Luoqi , Hu Ziwei , Zhang Shuoqi , Yang Sheng , Tao Yu , Xie Cuihong , Ma Ke , Shang Ke , Wang Wei , Tian Dai-Shi
Published: March 2020

Background

In December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China.

Methods

Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from 10 January to 12 February 2020 were collected and analyzed. The data on laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between patients with severe and nonsevere infection.

Results

Of the 452 patients with COVID-19 recruited, 286 were diagnosed as having severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough, and myalgia. Severe cases tend to have lower lymphocyte counts, higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and were more impaired in severe cases. Both helper T (Th) cells and suppressor T cells in patients with COVID-19 were below normal levels, with lower levels of Th cells in the severe group. The percentage of naive Th cells increased and memory Th cells decreased in severe cases. Patients with COVID-19 also have lower levels of regulatory T cells, which are more obviously decreased in severe cases.

Conclusions

The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19.
Salivary AMY1 Copy Number Variation Modifies Age-Related Type 2 Diabetes Risk
Authors: Liu Yuwei , Smith Caren E , Parnell Laurence D , Lee Yu-Chi , An Ping , Straka Robert J , Tiwari Hemant K , Wood Alexis C , Kabagambe Edmond K , Hidalgo Bertha , Hopkins Paul N , Province Michael A , Arnett Donna K , Tucker Katherine L , Ordovas Jose M , Lai Chao-Qiang
Published: March 2020

Background

Copy number variation (CNV) in the salivary amylase gene (AMY1) modulates salivary α-amylase levels and is associated with postprandial glycemic traits. Whether AMY1-CNV plays a role in age-mediated change in insulin resistance (IR) is uncertain.

Methods

We measured AMY1-CNV using duplex quantitative real-time polymerase chain reaction in two studies, the Boston Puerto Rican Health Study (BPRHS, n = 749) and the Genetics of Lipid-Lowering Drug and Diet Network study (GOLDN, n = 980), and plasma metabolomic profiles in the BPRHS. We examined the interaction between AMY1-CNV and age by assessing the relationship between age with glycemic traits and type 2 diabetes (T2D) according to high or low copy numbers of the AMY1 gene. Furthermore, we investigated associations between metabolites and interacting effects of AMY1-CNV and age on T2D risk.

Results

We found positive associations of IR with age among subjects with low AMY1-copy-numbers in both studies. T2D was marginally correlated with age in participants with low AMY1-copy-numbers but not with high AMY1-copy-numbers in the BPRHS. Metabolic pathway enrichment analysis identified the pentose metabolic pathway based on metabolites that were associated with both IR and the interactions between AMY1-CNV and age. Moreover, in older participants, high AMY1-copy-numbers tended to be associated with lower levels of ribonic acid, erythronic acid, and arabinonic acid, all of which were positively associated with IR.

Conclusions

We found evidence supporting a role of AMY1-CNV in modifying the relationship between age and IR. Individuals with low AMY1-copy-numbers tend to have increased IR with advancing age.
Broad-spectrum light pollution suppresses melatonin and increases West Nile virus–induced mortality in House Sparrows (Passer domesticus)
Authors: Kernbach Meredith E , Cassone Vincent M , Unnasch Thomas R , Martin Lynn B
Published: March 2020

Artificial light at night (ALAN) has become a pervasive anthropogenic stressor for both humans and wildlife. Although many negative impacts of ALAN on human health have been identified, the consequences for infectious disease dynamics are largely unexplored. With the increase in popularity of energy efficient light-emitting diodes (LEDs), the effects of spectral composition of ALAN have also come into question. Previous studies showed that exposure to low levels of incandescent ALAN extended the infectious period of House Sparrows (Passer domesticus) infected with West Nile virus (WNV) without affecting mortality rates, thus increasing the pathogen initial reproductive rate (R0) by ~41%. Here, we asked whether exposure to broad-spectrum (3000 K [Kelvin; unit of color temperature]) ALAN suppressed melatonin, a hormone implicated in ALAN-induced physiological consequences, in House Sparrows. We then asked whether amber-hue bulbs (1800 K) could ameliorate the effects of WNV on individual sparrows, and whether broad-spectrum or blue-rich bulbs (3000 K and 5000 K, respectively) could exacerbate them. We found that exposure to low intensity (~5 lux) broad-spectrum (3000 K) ALAN significantly suppressed melatonin levels throughout the night. Second, we found that exposure to broad-spectrum and blue-rich (3000 + 5000 K) lights did not affect WNV viremia but did increase WNV-induced mortality. Conversely, birds exposed to amber-hue (1800 K) ALAN had lower viremia and mortality rates similar to controls (i.e. natural light conditions). This study demonstrates that ALAN affects melatonin regulation in birds, but this effect, as well as ALAN influences on infectious disease responses, can be ameliorated by particular lighting technologies.
Case report: intravascular ultrasound sonography-guided re-entry technique in crushed stent
Authors: Iannaccone Mario , Barbero Umberto , De Benedictis Michele , D’ascenzo Fabrizio
Published: March 2020

Background

Stent thrombosis (ST) is a rare, but potentially fatal complication. Procedural problems, such as stent under-dimension/under-expansion or dual antiplatelet drug resistance may result into ST. These conditions are more frequent during primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI).

Case summary

A 60-year-old male patient presented to our hospital with an inferior STEMI. In the emergency department, a dual antiplatelet therapy was administered with ticagrelor 180 mg and aspirin 250 mg IV. During the observation, the patient experienced a ventricular fibrillation. Urgent coronary angiography showed an occlusion of the proximal right coronary artery. Thrombus aspiration was performed followed by implantation of one drug-eluting stent. After 45 min early ST occurred and was treated by immediate thrombus aspiration and post-dilatation. Intravascular ultrasound sonography (IVUS) showed severe strut malapposition due to a partial crush after post-dilatation. Since it was not possible to directly insert the first guidewire in the stent lumen, the IVUS probe was placed between the vessel wall and the crushed stent to guide the manoeuvre.

Discussion

Crushed stent is a rare complication, being caused by an incorrect passage of the guidewire between the stent’s struts and the vessel wall in case of severe underexpansion. In this case, an IVUS-guided re-entry could be an option to gain the stent true lumen and avoid a second stent implantation.
Risk prediction models for out-of-hospital cardiac arrest outcomes in England
Authors: Ji Chen , Brown Terry P , Booth Scott J , Hawkes Claire , Nolan Jerry P , Mapstone James , Fothergill Rachael T , Spaight Robert , Black Sarah , Perkins Gavin D ,   OHCAO Collaborators, Foster Theresa , Mersom Frank , Francis Gurkamal , O’Rourke Michelle , Bradley Clare , King Philip , Bucher Patricia , Lynde Jessica , Lumley-Holmes Jenny , Mark Julian
Published: March 2020

Aims

The out-of-hospital cardiac arrest (OHCA) outcomes project is a national research registry. One of its aims is to explore sources of variation in OHCA survival outcomes. This study reports the development and validation of risk prediction models for return of spontaneous circulation (ROSC) at hospital handover and survival to hospital discharge.

Methods and results

The study included OHCA patients who were treated during 2014 and 2015 by emergency medical services (EMS) from seven English National Health Service ambulance services. The 2014 data were used to identify important variables and to develop the risk prediction models, which were validated using the 2015 data. Model prediction was measured by area under the curve (AUC), Hosmer–Lemeshow test, Cox calibration regression, and Brier score. All analyses were conducted using mixed-effects logistic regression models. Important factors included age, gender, witness/bystander cardiopulmonary resuscitation (CPR) combined, aetiology, and initial rhythm. Interaction effects between witness/bystander CPR with gender, aetiology and initial rhythm and between aetiology and initial rhythm were significant in both models. The survival model achieved better discrimination and overall accuracy compared with the ROSC model (AUC = 0.86 vs. 0.67, Brier score = 0.072 vs. 0.194, respectively). Calibration tests showed over- and under-estimation for the ROSC and survival models, respectively. A sensitivity analysis individually assessing Index of Multiple Deprivation scores and location in the final models substantially improved overall accuracy with inconsistent impact on discrimination.

Conclusion

Our risk prediction models identified and quantified important pre-EMS intervention factors determining survival outcomes in England. The survival model had excellent discrimination.
Simple electrocardiographic measures improve sudden arrhythmic death prediction in coronary disease
Authors: Chatterjee Neal A , Tikkanen Jani T , Panicker Gopi K , Narula Dhiraj , Lee Daniel C , Kentta Tuomas , Junttila Juhani M , Cook Nancy R , Kadish Alan , Goldberger Jeffrey J , Huikuri Heikki V , Albert Christine M ,   for the PREDETERMINE Investigators
Published: March 2020

Aims

To determine whether the combination of standard electrocardiographic (ECG) markers reflecting domains of arrhythmic risk improves sudden and/or arrhythmic death (SAD) risk stratification in patients with coronary heart disease (CHD).

Methods and results

The association between ECG markers and SAD was examined in a derivation cohort (PREDETERMINE; N = 5462) with adjustment for clinical risk factors, left ventricular ejection fraction (LVEF), and competing risk. Competing outcome models assessed the differential association of ECG markers with SAD and competing mortality. The predictive value of a derived ECG score was then validated (ARTEMIS; N = 1900). In the derivation cohort, the 5-year cumulative incidence of SAD was 1.5% [95% confidence interval (CI) 1.1–1.9] and 6.2% (95% CI 4.5–8.3) in those with a low- and high-risk ECG score, respectively (P for Δ < 0.001). A high-risk ECG score was more strongly associated with SAD than non-SAD mortality (adjusted hazard ratios = 2.87 vs. 1.38 respectively; P for Δ = 0.003) and the proportion of deaths due to SAD was greater in the high vs. low risk groups (24.9% vs. 16.5%, P for Δ = 0.03). Similar findings were observed in the validation cohort. The addition of ECG markers to a clinical risk factor model inclusive of LVEF improved indices of discrimination and reclassification in both derivation and validation cohorts, including correct reclassification of 28% of patients in the validation cohort [net reclassification improvement 28 (7–49%), P = 0.009].

Conclusion

For patients with CHD, an externally validated ECG score enriched for both absolute and proportional SAD risk and significantly improved risk stratification compared to standard clinical risk factors including LVEF.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT01114269. ClinicalTrials.gov ID NCT01114269.
Hypertensive coronary microvascular dysfunction: a subclinical marker of end organ damage and heart failure
Authors: Zhou Wunan , Brown Jenifer M , Bajaj Navkaranbir S , Chandra Alvin , Divakaran Sanjay , Weber Brittany , Bibbo Courtney F , Hainer Jon , Taqueti Viviany R , Dorbala Sharmila , Blankstein Ron , Adler Dale , O’Gara Patrick , Di Carli Marcelo F
Published: March 2020

Aims

Hypertension is a well-established heart failure (HF) risk factor, especially in the context of adverse left ventricular (LV) remodelling. We aimed to use myocardial flow reserve (MFR) and global longitudinal strain (GLS), markers of subclinical microvascular and myocardial dysfunction, to refine hypertensive HF risk assessment.

Methods and results

Consecutive patients undergoing symptom-prompted stress cardiac positron emission tomography (PET)-computed tomography and transthoracic echocardiogram within 90 days without reduced left ventricular ejection fraction (<40%) or flow-limiting coronary artery disease (summed stress score ≥ 3) were included. Global MFR was quantified by PET, and echocardiograms were retrospectively analysed for cardiac structure and function. Patients were followed over a median 8.75 (Q1–3 4.56–10.04) years for HF hospitalization and a composite of death, HF hospitalization, MI, or stroke. Of 194 patients, 155 had adaptive LV remodelling while 39 had maladaptive remodelling, which was associated with lower MFR and impaired GLS. Across the remodelling spectrum, diastolic parameters, GLS, and N-terminal pro-B-type natriuretic peptide were independently associated with MFR. Maladaptive LV remodelling was associated with increased adjusted incidence of HF hospitalization and death. Importantly, the combination of abnormal MFR and GLS was associated with a higher rate of HF hospitalization compared to normal MFR and GLS [adjusted hazard ratio (HR) 3.21, 95% confidence interval (CI) 1.09–9.45, P = 0.034), including in the adaptive remodelling subset (adjusted HR 3.93, 95% CI 1.14–13.56, P = 0.030).

Conclusion

We have demonstrated important associations between coronary microvascular dysfunction and myocardial mechanics that refine disease characterization and HF risk assessment of patients with hypertension based on subclinical target organ injury.
Functional tricuspid regurgitation of degenerative mitral valve disease: a crucial determinant of survival
Authors: Essayagh Benjamin , Antoine Clémence , Benfari Giovanni , Maalouf Joseph , Michelena Hector I , Crestanello Juan A , Thapa Prabin , Avierinos Jean-François , Enriquez-Sarano Maurice
Published: March 2020

Aims 

To assess functional tricuspid regurgitation (FTR) determinants, consequences, and independent impact on outcome in degenerative mitral regurgitation (DMR).

Methods and results 

All patients diagnosed with isolated DMR 2003–2011, with structurally normal tricuspid leaflets, prospective FTR grading and systolic pulmonary artery pressure (sPAP) estimation by Doppler echocardiography at diagnosis were identified and long-term outcome analysed. The 5083 DMR eligible patients [63 ± 16 years, 47% female, ejection fraction (EF) 63 ± 7%, and sPAP 35 ± 13 mmHg] presented with FTR graded trivial in 45%, mild in 37%, moderate in 15%, and severe in 3%. While pulmonary hypertension (PHTN-sPAP ≥ 50 mmHg) was the most powerful FTR severity determinant, other strong FTR determinants were older age, female sex, lower left ventricle EF, DMR, and particularly atrial fibrillation (AFib) (all P ≤ 0.002). Functional tricuspid regurgitation moderate/severe was independently linked to more severe clinical presentation, more oedema, lower stroke volume, and impaired renal function (P ≤ 0.01). Survival (95% confidence interval) throughout follow-up [70% (69–72%) at 10 years] was strongly associated with FTR severity [82% (80–84%) for trivial, 69% (66–71%) for mild, 51% (47–57%) for moderate, and 26% (19–35%) for severe, P < 0.0001]. Excess mortality persisted after comprehensive adjustment [adjusted hazard ratio 1.40 (1.18–1.67) for moderate FTR and 2.10 (1.63–2.70) for severe FTR, P ≤ 0.01]. Excess mortality persisted adjusting for sPAP/right ventricular function (P < 0.0001), by matching [adjusted hazard ratios 2.08 (1.50–2.89), P < 0.0001] and vs. expected survival [risk ratio 1.79 (1.48–2.16), P < 0.0001]. Within 5-year of diagnosis valve surgery was performed in 73% (70–75%) and 15% (13–17%) of severe and moderate DMR and in only 26% (19–34%) and 6% (4–8%) of severe and moderate FTR. Valvular surgery improved outcome without alleviating completely higher mortality associated with FTR (P < 0.0001).

Conclusion 

In this large DMR cohort, FTR was frequent and causally, not only linked to PHTN but also to other factors, particularly AFib. Higher FTR severity is associated at diagnosis with more severe clinical presentation. Long term, FTR is independently of all confounders, associated with considerably worse mortality. Functional tricuspid regurgitation moderate and even severe is profoundly undertreated. Thus careful assessment, consideration for tricuspid surgery, and testing of new transcatheter therapy is warranted.
Genetic predisposition to smoking in relation to 14 cardiovascular diseases
Authors: Larsson Susanna C , Mason Amy M , Bäck Magnus , Klarin Derek , Damrauer Scott M ,   Million Veteran Program, Michaëlsson Karl , Burgess Stephen
Published: March 2020

Aims

The aim of this study was to use Mendelian randomization (MR) to determine the causality of the association between smoking and 14 different cardiovascular diseases (CVDs).

Methods and results

Our primary genetic instrument comprised 361 single-nucleotide polymorphisms (SNPs) associated with smoking initiation (ever smoked regularly) at genome-wide significance. Data on the associations between the SNPs and 14 CVDs were obtained from the UK Biobank study (N = 367 643 individuals), CARDIoGRAMplusC4D consortium (N = 184 305 individuals), Atrial Fibrillation Consortium (2017 dataset; N = 154 432 individuals), and Million Veteran Program (MVP; N = 190 266 individuals). The main analyses were conducted using the random-effects inverse-variance weighted method and complemented with multivariable MR analyses and the weighted median and MR-Egger approaches. Genetic predisposition to smoking initiation was most strongly and consistently associated with higher odds of coronary artery disease, heart failure, abdominal aortic aneurysm, ischaemic stroke, transient ischaemic attack, peripheral arterial disease, and arterial hypertension. Genetic predisposition to smoking initiation was additionally associated with higher odds of deep vein thrombosis and pulmonary embolism in the UK Biobank but not with venous thromboembolism in the MVP. There was limited evidence of causal associations of smoking initiation with atrial fibrillation, aortic valve stenosis, thoracic aortic aneurysm, and intracerebral and subarachnoid haemorrhage.

Conclusion

This MR study supports a causal association between smoking and a broad range of CVDs, in particular, coronary artery disease, heart failure, abdominal aortic aneurysm, ischaemic stroke, transient ischaemic attack, peripheral arterial disease, and arterial hypertension.
Differences in housing transitions and changes in health and self-determination between formerly homeless individuals
Authors: van der Laan Jorien , Boersma Sandra N , al Shamma Sara , Akkermans Reinier , van Straaten Barbara , Rodenburg Gerda , van de Mheen Dike , Wolf Judith R L M
Published: March 2020

Background

To reduce homelessness, it is important to gain a better understanding of the differences between homeless people who remain in institutions and those who gain and can sustain independent housing. This longitudinal study explores differences in housing transitions and differences in changes in health and self-determination between formerly homeless people still living in institutions 2.5 years later and those now living in independent housing in the Netherlands.

Methods

This study mapped the housing transitions of 263 participants from when they entered the social relief system (SRS) to 2.5 years later when they were in independent housing or institutions. These individuals were compared at the 2.5-year mark in terms of gender, age and retrospectively in terms of duration of homelessness. They were also compared with regard to changes in psychological distress, perceived health, substance use and self-determination.

Results

Two and a half years after entering the SRS, 81% of participants were independently housed and 19% still lived in institutions. People in institutions had a longer lifetime duration of homelessness, were more often men, and their number of days of alcohol use had decreased significantly more, whereas independently housed people had shown a significant increase in their sense of autonomy and relatedness.

Conclusion

Formerly homeless people living in independent housing and in institutions show few health-related differences 2.5 years after entering the SRS, but changes in autonomy and relatedness are distinctly more prevalent, after the same period of time, in those who are independently housed.
New ECCO model documents for Material Deposit and Transfer Agreements in compliance with the Nagoya Protocol
Authors: Verkley Gerard , Perrone Giancarlo , Piña Mery , Scholz Amber Hartman , Overmann Jörg , Zuzuarregui Aurora , Perugini Iolanda , Turchetti Benedetta , Hendrickx Marijke , Stacey Glyn , Law Samantha , Russell Julie , Smith David , Lima Nelson
Published: March 2020

The European Culture Collections’ Organisation presents two new model documents for Material Deposit Agreement (MDA) and Material Transfer Agreement (MTA) designed to enable microbial culture collection leaders to draft appropriate agreement documents for, respectively, deposit and supply of materials from a public collection. These tools provide guidance to collections seeking to draft an MDA and MTA, and are available in open access to be used, modified, and shared. The MDA model consists of a set of core fields typically included in a ‘deposit form’ to collect relevant information to facilitate assessment of the status of the material under access and benefit sharing (ABS) legislation. It also includes a set of exemplary clauses to be included in ‘terms and conditions of use’ for culture collection management and third parties. The MTA model addresses key issues including intellectual property rights, quality, safety, security and traceability. Reference is made to other important tools such as best practices and code of conduct related to ABS issues. Besides public collections, the MDA and MTA model documents can also be useful for individual researchers and microbial laboratories that collect or receive microbial cultures, keep a working collection, and wish to share their material with others.
Gendering South Africa's Foreign Policy: Toward a Feminist Approach?
Authors: Haastrup Toni
Published: March 2020

South Africa's leadership has sought ethical foreign policy since the advent of democracy. This foreign policy outlook focuses on the African continent and includes certain articulations of pro-gender justice norms. In this article, I reflect on the extent to which South Africa's foreign policy embraces these norms as part of its foreign apparatus and practices. It takes at its starting point the nascent literature on feminist foreign policy applied to South Africa, which shares similarities to countries in the Global North that claim a feminist orientation to foreign policy. Moreover, it takes account of gender dynamics at the domestic level and how they are manifested in foreign policy discourses and practices, particularly in the understanding and implementation of the Women, Peace, and Security agenda. Utilizing qualitative content analysis, this article provides context and meaning for how gender concerns have evolved in South Africa's foreign policy, including the role of certain norm entrepreneurs in shaping the gender narrative. The article concludes that the domestic context is important to shaping and limiting how a country can enact feminist foreign policy. Importantly, the South African case provides a Global South dimension to the nascent scholarship.
Intervention Characteristics Associated With a Reduction in Fear of Falling Among Community-Dwelling Older People: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Kruisbrink Marlot , Delbaere Kim , Kempen Gertrudis I J M , Crutzen Rik , Ambergen Ton , Cheung Kei-Long , Kendrick Denise , Iliffe Steve , Zijlstra G A Rixt
Published: March 2020

Background and Objectives

Fear of falling (FoF) is associated with decreased physical functioning and an increased fall risk. Interventions generally demonstrate moderate effects and optimized interventions are needed. Intervention characteristics, such as setting or delivery method may vary. We investigated which overarching intervention characteristics are associated with a reduction in FoF in community-dwelling older people.

Research Design and Methods

A systematic review and meta-analysis of randomized controlled trials (RCTs) in community-dwelling older people without specific diseases was performed. Associations between intervention characteristics and standardized mean differences (SMD) were determined by univariate meta-regression. Sensitivity analyses were performed.

Results

Data on 62 RCTs were extracted, 50 intervention groups were included in the meta-analysis. Most intervention characteristics and intervention types were not associated with the intervention effect. Supervision by a tai chi instructor (SMD: −1.047, 95% confidence interval [CI]: −1.598; −0.496) and delivery in a community setting (SMD: −0.528, 95% CI: −0.894; −0.161) were—compared to interventions without these characteristics—associated with a greater reduction in FoF. Holistic exercise, such as Pilates or yoga (SMD: −0.823, 95% CI: −1.255; −0.392), was also associated with a greater reduction in FoF. Delivery at home (SMD: 0.384, 95% CI: 0.002; 0.766) or with written materials (SMD: 0.452, 95% CI: 0.088; 0.815) and tailoring were less effective in reducing FoF (SMD: 0.687, 95% CI: 0.364; 1.011).

Discussion and Implications

Holistic exercise, delivery with written materials, the setting and tailoring potentially represent characteristics to take into account when designing and improving interventions for FoF in community-dwelling older people. PROSPERO international prospective register of systematic reviews, registration ID CRD42018080483.
Aging in New Zealand: Ka haere ki te ao pakeketanga
Authors: Parr-Brownlie Louise C , Waters Debra L , Neville Stephen , Neha Tia , Muramatsu Naoko
Published: March 2020

Aotearoa-New Zealand is expecting the number of older adults to double in the next 20 years. Despite publicly funded health and welfare support for older citizens, the aging experience differs across ethnic groups. This creates opportunities and challenges for health and social services to deliver culturally safe and equitable care for all older New Zealanders. Longitudinal and large data sets are pivotal for characterizing the aging experience from birth to advanced age. The New Zealand research funding system responded to predicted demographic changes by increasing funding in order to inform and address key health and well-being issues for older people. In addition, government strategies and policies increasingly focus on social aspects of aging and health inequities and require researchers and organizations to be better connected to end-users. New Zealand needs to continue to fund research that identifies unique and courageous service delivery solutions that result in positive social, financial, psychological, and physical aging for older New Zealanders.
Correlates of participation in physical activity among older women in Israel: does ethno-cultural background matter?
Authors: Edelstein Offer E , Vered Iris , Sarid Orly
Published: March 2020

Osteoporosis and its related fractures are major public health concerns. Physical activity (PA) is crucial for bone density preservation and fractures prevention. Yet, gaps in understanding exist regarding how ethno-cultural backgrounds might shape attitudes, intentions and actual PA participation. Based on the theory of planned behaviour (TPB) for predicting PA, the aims of this study were: (i) to compare attitudes, subjective norms, perceived control, intentions and knowledge, across four ethno-cultural groups; (ii) to evaluate the fit of the model we constructed across four ethno-cultural groups of women: Israeli-born Jews and Israeli-born Bedouin-Muslims, immigrants from the Former Soviet Union (FSU) and Ethiopian immigrants. Four hundred women (one hundred from each group), aged >65, completed valid and reliable questionnaires assessing knowledge, TPB components and actual PA. The level of knowledge on osteoporosis was relatively low among all four ethno-cultural groups. Intention to participate in PA was the only variable that directly predicted actual PA. Intention to participate in PA served as a mediator among attitudes, subjective norms, perceived control and actual PA. The structural equation models (SEMs) revealed that among Israeli-born Jews and Ethiopian immigrants, TPB components mediated the link between knowledge and intention to participate in PA. Among FSU immigrants and Israeli Bedouin-Muslims, the knowledge variable was not included in the final model, as its contribution was not significant. It is essential to better understand and augment interventions that enhance PA in the community, and to address the unique needs of each ethno-cultural group.
Demonstration of brain region-specific neuronal vulnerability in human iPSC-based model of familial Parkinson’s disease
Authors: Brazdis Razvan-Marius , Alecu Julian E , Marsch Daniel , Dahms Annika , Simmnacher Katrin , Lörentz Sandra , Brendler Anna , Schneider Yanni , Marxreiter Franz , Roybon Laurent , Winner Beate , Xiang Wei , Prots Iryna
Published: March 2020

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by protein inclusions mostly composed of aggregated forms of α-synuclein (α-Syn) and by the progressive degeneration of midbrain dopaminergic neurons (mDANs), resulting in motor symptoms. While other brain regions also undergo pathologic changes in PD, the relevance of α-Syn aggregation for the preferential loss of mDANs in PD pathology is not completely understood yet. To elucidate the mechanisms of the brain region-specific neuronal vulnerability in PD, we modeled human PD using human-induced pluripotent stem cells (iPSCs) from familial PD cases with a duplication (Dupl) of the α-Syn gene (SNCA) locus. Human iPSCs from PD Dupl patients and a control individual were differentiated into mDANs and cortical projection neurons (CPNs). SNCA dosage increase did not influence the differentiation efficiency of mDANs and CPNs. However, elevated α-Syn pathology, as revealed by enhanced α-Syn insolubility and phosphorylation, was determined in PD-derived mDANs compared with PD CPNs. PD-derived mDANs exhibited higher levels of reactive oxygen species and protein nitration levels compared with CPNs, which might underlie elevated α-Syn pathology observed in mDANs. Finally, increased neuronal death was observed in PD-derived mDANs compared to PD CPNs and to control mDANs and CPNs. Our results reveal, for the first time, a higher α-Syn pathology, oxidative stress level, and neuronal death rate in human PD mDANs compared with PD CPNs from the same patient. The finding implies the contribution of pathogenic α-Syn, probably induced by oxidative stress, to selective vulnerability of substantia nigra dopaminergic neurons in human PD.
Recapitulation of the EEF1A2 D252H neurodevelopmental disorder-causing missense mutation in mice reveals a toxic gain of function
Authors: Davies Faith C J , Hope Jilly E , McLachlan Fiona , Marshall Grant F , Kaminioti-Dumont Laura , Qarkaxhija Vesa , Nunez Francis , Dando Owen , Smith Colin , Wood Emma , MacDonald Josephine , Hardt Oliver , Abbott Catherine M
Published: March 2020

Heterozygous de novo mutations in EEF1A2, encoding the tissue-specific translation elongation factor eEF1A2, have been shown to cause neurodevelopmental disorders including often severe epilepsy and intellectual disability. The mutational profile is unusual; ~50 different missense mutations have been identified but no obvious loss of function mutations, though large heterozygous deletions are known to be compatible with life. A key question is whether the heterozygous missense mutations operate through haploinsufficiency or a gain of function mechanism, an important prerequisite for design of therapeutic strategies. In order both to address this question and to provide a novel model for neurodevelopmental disorders resulting from mutations in EEF1A2, we created a new mouse model of the D252H mutation. This mutation causes the eEF1A2 protein to be expressed at lower levels in brain but higher in muscle in the mice. We compared both heterozygous and homozygous D252H and null mutant mice using behavioural and motor phenotyping alongside molecular modelling and analysis of binding partners. Although the proteomic analysis pointed to a loss of function for the D252H mutant protein, the D252H homozygous mice were more severely affected than null homozygotes on the same genetic background. Mice that are heterozygous for the missense mutation show no behavioural abnormalities but do have sex-specific deficits in body mass and motor function. The phenotyping of our novel mouse lines, together with analysis of molecular modelling and interacting proteins, suggest that the D252H mutation results in a gain of function.
ESHRE PGT Consortium good practice recommendations for the detection of structural and numerical chromosomal aberrations†
Authors:   ESHRE PGT-SR/PGT-A Working Group, Coonen Edith , Rubio Carmen , Christopikou Dimitra , Dimitriadou Eftychia , Gontar Julia , Goossens Veerle , Maurer Maria , Spinella Francesca , Vermeulen Nathalie , De Rycke Martine
Published: March 2020

The field of preimplantation genetic testing (PGT) is evolving fast, and best practice advice is essential for regulation and standardisation of diagnostic testing. The previous ESHRE guidelines on best practice for PGD, published in 2005 and 2011, are considered outdated, and the development of new papers outlining recommendations for good practice in PGT was necessary. The current paper provides recommendations on the technical aspects of PGT for chromosomal structural rearrangements (PGT-SR) and PGT for aneuploidies (PGT-A) and covers recommendations on array-based comparative genomic hybridisation (aCGH) and next-generation sequencing (NGS) for PGT-SR and PGT-A and on fluorescence in situ hybridisation (FISH) and single nucleotide polymorphism (SNP) array for PGT-SR, including laboratory issues, work practice controls, pre-examination validation, preclinical work-up, risk assessment and limitations. Furthermore, some general recommendations on PGT-SR/PGT-A are formulated around training and general risk assessment, and the examination and post-examination process. This paper is one of a series of four papers on good practice recommendations on PGT. The other papers cover the organisation of a PGT centre, embryo biopsy and tubing and the technical aspects of PGT for monogenic/single-gene defects (PGT-M).

Together, these papers should assist everyone interested in PGT in developing the best laboratory and clinical practice possible.
Rankine-type cylinders having zero wave resistance in infinitely deep flows
Authors: Dambrine Julien , Noviani Evi , Pierre Morgan
Published: March 2020

We prove the existence of a family of immersed obstacles that have zero wave resistance in the context of the 2D Neumann–Kelvin problem. We first build a waveless potential by superposing a source and a sink in a uniform flow for an appropriate choice of parameters. The obstacle is obtained by a combination of streamlines of the waveless potential. Numerical simulations show that the construction is valid for a large set of parameters.