Marked Regional Variation Research Articles

Agglomeration Externalities vs. Network Externalities: Impact on Green Technology Innovation in 283 Chinese Cities

The prominence of agglomeration externalities (AEs) and network externalities (NEs) in urban sustainable development has intensified in recent times, with advances in transportation infrastructure and information technology acting as key accelerators. Despite the scholarly attention they receive, the specific spillover effects that these externalities exert on green technology innovation (GTI) remain under-explored. In an effort to bridge this knowledge gap, the present study employs a spatial Durbin model to scrutinize, spanning a decade from 2011 to 2021, the impact and spatial spillover of AEs and NEs on GTI across 283 Chinese cities of prefecture level and above. The findings reveal the following: (1) AEs exert a U-shaped influence on GTI, initially inhibiting it, before ultimately fostering its growth. (2) NEs are found to consistently promote GTI. (3) The spatial spillover effects of AEs on GTI are significantly positive, while those from NEs are not statistically significant. (4) The influences of AEs and NEs on GTI exhibit marked regional variations. This study extends the research scope on the factors influencing GTI by examining the role of AEs and NEs, thereby aiming to offer valuable insights for enhancing the level of GTI.

Variation in antibiotic consumption in very preterm infants-a 10 year population-based study.

Wide variations in antibiotic use in very preterm infants have been reported across centres despite similar rates of infection. We describe 10 year trends in use of antibiotics and regional variations among very preterm infants in Norway. All live-born very preterm infants (<32 weeks gestation) admitted to any neonatal unit in Norway during 2009-18 were included. Main outcomes were antibiotic consumption expressed as days of antibiotic therapy (DOT) per 1000 patient days (PD), regional variations in use across four health regions, rates of sepsis and sepsis-attributable mortality and trends of antibiotic use during the study period. We included 5296 infants: 3646 (69%) were born at 28-31 weeks and 1650 (31%) were born before 28 weeks gestation with similar background characteristics across the four health regions. Overall, 80% of the very preterm infants received antibiotic therapy. The most commonly prescribed antibiotics were the combination of narrow-spectrum β-lactams and aminoglycosides, but between 2009 and 2018 we observed a marked reduction in their use from 100 to 40 DOT per 1000 PD (P < 0.001). In contrast, consumption of broad-spectrum β-lactams remained unchanged (P = 0.308). There were large variations in consumption of vancomycin, broad-spectrum β-lactams and first-generation cephalosporins, but no differences in sepsis-attributable mortality across regions. The overall antibiotic consumption was reduced during the study period. Marked regional variations remained in consumption of broad-spectrum β-lactams and vancomycin, without association to sepsis-attributable mortality. Our results highlight the need for antibiotic stewardship strategies to reduce consumption of antibiotics that may enhance antibiotic resistance development.

Epidemiology of alopecia areata and population-wide comorbidities in Germany: analysis of longitudinal claimsdata.

Alopecia areata (AA) is a chronic, immune-mediated disease characterized by acute-onset hair loss. The hair loss can range from small, circumscribed hairless areas on the scalp to complete loss of hair on the head and body hair. However, data on the epidemiology of AA are limited. Current evaluations are lacking in Germany. The aim of this study was to evaluate the epidemiology and comorbidity of AA in Germany based on claims data. A representative 40% sample of all adults who were insured with a German statutory health insurance company (DAK-Gesundheit) between 2016 and 2020 was evaluated (n = 2.88 million). Based on at least one relevant outpatient or inpatient diagnosis of International Classification of Diseases (ICD)-10 L63, the annual AA prevalence and incidence (ICD-10 L63) were calculated for 2016 to 2020. Different case definitions were used for diagnosis validation. In addition, the occurrence of comorbidities in patients with AA was investigated. In 2020, AA prevalence was 210 cases per 100 000 and incidence 72 cases per 100 000. Compared with persons without AA, those with AA significantly more often had atopic dermatitis [rate ratio (RR) 2.9], pruritus (RR 2.7), lupus erythematosus (RR 2.4), urticaria (RR2.3) and psoriasis (RR 2.2). Women were affected slightly more often than men (0.2% vs. 0.1%). On a regional level, higher prevalence and incidence rates were found in Brandenburg (prevalence 332 cases per 100 000; incidence 116 cases per 100 000), Hesse (prevalence 344cases per 100 000; incidence 124 cases per 100 000) and Mecklenburg-Western Pomerania (prevalence 303 cases per 100 000; incidence 111per100 000). AA is a common immune-mediated skin condition with marked regional variations in Germany. For a complete understanding of epidemiology, complementary population-based studies including clinical characteristics of AA are useful.

Global epidemiological trends and variations in the burden of gallbladder cancer.

Gallbladder cancer (GBC) is a rare but lethal malignancy with a dismal prognosis. The aim of this study is to analyze the burdens and trends of GBC across the world based on geography, socioeconomic development (based on human development index [HDI]), and gender. GLOBOCAN 2020 database was used to extract data (2020-2040) relating to the incidence and mortality of GBC across the world. Asia had the highest burden of GBC with India and China contributing to majority of the absolute burden. The burden of GBC by age standardized rate was highest in Latin America (Bolivia and Chile) and Southeast Asia (Bangladesh and Nepal). Medium HDI countries had a higher mortality rate compared to very high HDI countries. Females had a higher predilection for GBC across different regions and socioeconomic groups. GBC burden is expected to significantly increase across the world by 2040 with variable trends across different regions, age groups, and genders. The global burden of GBC will significantly increase over the next two decades with marked regional and demographic variations. The results of this study will empower national and global health leaders to develop policies to address the increasing burden of this lethal malignancy.

A Spatial Variation Analysis of In-Hospital Stroke Mortality Based on Integrated Pre-Hospital and Hospital Data in Mashhad, Iran.

Despite significant advances in the quality and delivery of specialized stroke care, there still persist remarkable spatial variations in emergency medical services (EMS) transport delays, stroke incidence, and its outcomes. Therefore, it is very important to investigate the possible geographical variations of in-hospital stroke mortality and to identify its associated factors. This historical cohort study included suspected stroke cases transferred to Ghaem Hospital of Mashhad by the EMS from March 2018 to March 2019. Using emergency mission IDs, the pre-hospital emergency data were integrated with the patient medical records in the hospital. We used the Bayesian approach for estimating the model parameters. Out of 301 patients (142 (47.2%) females vs. 159 (52.8%) males) with a final diagnosis of stroke, 61 (20.3%) cases had in-hospital mortality. Results from Bayesian spatial log-logistic proportional odds (PO) model showed that age (PO=1.07), access rate to EMS (PO=0.78), arrival time (evening shift vs. day shift, PO=0.09), and sequelae variables (PO=9.20) had a significant association with the odds of in-hospital stroke mortality (P<0.05). Furthermore, the odds of in-hospital stroke mortality were higher in central urban areas compared to suburban areas. Marked regional variations were found in the odds of in-hospital stroke mortality in Mashhad. There was a direct association between age and odds of in-hospital stroke mortality. Hence, the prognosis of in-hospital stroke mortality could be improved by better control of hypertension, prevention of the occurrence of sequelae, increasing the access rate to EMS, and optimizing shift work schedule.

Analysis of KRAS Mutations in Gastrointestinal Tract Adenocarcinomas Reveals Site-Specific Mutational Signatures

Adenocarcinomas of the luminal gastrointestinal tract and pancreatobiliary system often show histologic and immunohistochemical overlap, making delineation of the primary site in a metastatic setting difficult. Previous studies have shown that site-specific missense mutations in the oncogene KRAS could be used in conjunction with immunohistochemistry to differentiate metastatic pancreatic adenocarcinoma from primary lung adenocarcinoma. In this study, we assessed the patterning of KRAS mutations across sites in the gastrointestinal and pancreatobiliary system. By integrating sequencing data from 44 separate studies, we assessed 2523 KRAS mutations in 7382 distinct cases of adenocarcinoma, including those from the esophagus, stomach, ampulla, biliary system, pancreas, and colon. We found that gastrointestinal adenocarcinomas demonstrate a marked regional variation in the frequency of KRAS mutations, with the most frequent KRAS mutation observed in pancreatic adenocarcinoma (up to 94.9%), whereas the frequency is much lower in adenocarcinomas from the esophagus and stomach (5.4% and 8.7%, respectively). Intriguingly, the pattern of missense mutations showed site specificity as well, with c.35G>T (p.G12V) and c.34G>C (p.G12R) mutations enriched in pancreatic primaries and codon 13 and non–codon 12/13 alterations enriched in gastric primaries (specificity of 98.9% and 93.2%, respectively, with a negative predictive value of 93.6% and 92.93% against pancreatic adenocarcinoma). Furthermore, we found that esophageal and gastric adenocarcinomas show an enrichment in transitional mutations, whereas other sites showed an equal distribution. Importantly, the examination of a validation cohort from our own institution revealed similar trends. These findings indicate that, in addition to providing therapeutic and diagnostic information, KRAS mutational analysis may also prove useful in delineating the site of origin in gastrointestinal adenocarcinomas that share morphologic and immunohistochemical overlap. Moreover, transitional mutations are more frequent in esophageal and gastric adenocarcinomas, reiterating the role of chronic inflammation in the pathogenesis of foregut adenocarcinomas.

Predictors, Patterns, and Impact of Adequate Lymphadenectomy in Intrahepatic Cholangiocarcinoma.

Despite lymph node metastases (LNMs) being associated withworse survival, adequate lymph node evaluation (LNE) has notbeen universally adopted for intrahepatic cholangiocarcinoma (ICC). We sought to evaluate trends in LNE, predictors of LNE and LNM, as well as the role of adequate lymphadenectomy in stratifying patients relative tosurvival. Patients who underwent curative-intent liver resection for ICC (2010-2019) were identified from the National Cancer Database and stratified according to LNE: 0, 1-5 (inadequate lymphadenectomy) and ≥6 (adequate lymphadenectomy). Multivariate logistic regression was utilized to assess predictors of LNE and LNM. Overall survival and receipt of adequate lymphadenectomy were assessed relative to LNM and log-odds of lymph nodes(LODDS). Among 6507 patients, adequate lymphadenectomy was performed in only 1118 (17.2%) patients, although compliance with adequate lymphadenectomy increased over time (2010-2012: 14.2% vs. 2016-2019: 18.9%; p<0.001). After controlling for relevant factors, region (reference: Northeast; Midwest: odds ratio [OR] 1.90, 95% confidence interval [CI] 1.48-2.44; South: OR 1.64, 95% CI 1.28-2.10; West: OR 1.83, 95% CI 1.37-2.44) and preoperative nodal status (reference: cN0; cNx: OR 2.18, 95% CI 1.68-2.95; cN1: OR 3.88, 95% CI 3.02-4.98) strongly predicted adequate lymphadenectomy. Furthermore, adequate lymphadenectomy resulted in higher odds of detecting ≥1 LNMs (OR 2.63, 95% CI 2.25-3.08), regardless of preoperative nodal status. Adequate lymphadenectomy demonstrated animproved ability to stratify patients relative to5-yearsurvival based on LNM (N0: 51.3% vs. N1: 30.6% vs. N2: 13.7%; p<0.001) and LODDS (LODDS1: 50.7% vs. LODDS2: 27.4% vs. LODDS3: 15.7%; p<0.001). Compliance withadequate lymphadenectomyat the time of surgery for ICCremains suboptimal with marked regional variations. Adequate lymphadenectomy was associated with higher odds of detecting LNM and improved survival stratification relative to both LNM and LODDS. Greater emphasis on nodal evaluation is required to ensure optimal management of ICC.

Twenty‐five years of acanthamoeba diagnostics in Austria

AbstractAcanthamoeba spp. are ubiquitous free‐living amoebae and do not need a host. They can, however, cause disease upon accidental contact with a potential host. The most common Acanthamoeba infection in humans is the so‐called Acanthamoeba keratitis (AK), occurring mainly in contact lens wearers.The first case of AK was reported in the early seventies and in the mid‐eighties the association between AK and contact lens wear was discovered. Today, acanthamoebae are among the most important causative agents of keratitis in contact lens wearers. AK often shows a severe progression, which is due to a lack of awareness but also to the lack of specific treatment. The dormant cysts pose a particular problem, often residing within the tissue and leading to reinfection after termination of treatment. In industrialized countries the annual incidence of AK lies between 0.1–1 cases per 100 000 inhabitants, with a marked regional variation depending on contact lens wear habits and mode of water supply.Our institution is the Austrian reference laboratory for Acanthamoeba diagnostics. All samples from patients with suspected AK are screened for Acanthamoeba spp. by culture and PCR in parallel, and all detected amoebae are genotyped. We currently have an annual incidence of AK of around 0.2 cases per 100 000 inhabitants, with &gt;90% of cases occurring in contact lens wearers. In contrast to other countries, we do not see any seasonality and in contrast to the early years, today, males and females are equally represented, the most affected group being the 21–30‐year‐olds. The vast majority of cases are unilateral and many cases have a prolonged progression, in some cases infections remain viable for &gt;1 yr. The predominant genotype is Acanthamoeba T4, other common genotypes are T3, T5, T6, T10 and T11.

Regional variation and rising costs of groin hernia repairs in Australia: is there an urgent need for clinical consensus guidelines?

Regional variation and rising costs of groin hernia repairs in Australia: is there an urgent need for clinical consensus guidelines?

A Rare Case of Haemoglobin J-Toronto in a Child

Introduction: India is an ethnically diverse country with marked regional variation. This diversity is often reflected in the presence of different Hemoglobin variants. Hb variants arise due to mutations in the genes encoding for the α-chain and β-chain. Hb J is an infrequently found α-globin variant. It is a Fast moving hemoglobin. Haemoglobin J (Hb-J) was first described by Thorup et al. in an African-American patient (1956) and since then more than 50 variants of Hb-J are identified. Hb J-Toronto [alpha5(A3) Ala&gt;Asp] is one of the rare variants identified. Case report: Blood sample of one year old child for high-performance liquid chromatography was received. The HPLC showed an abnormally high peak in P3 window on BIO RAD D10 machine. The high-performance liquid chromatography showed normal hemoglobin Hb F and Hb A2, but showed elevated levels of P3 (31.7%) which indicates presence of a Hb J variant. Conclusion: Hb J-Toronto is a rare variant of abnormal hemoglobin. It has little clinical significance in heterozygous state but when combined with other variants, they may give rise to severe disease.Prenatal analysis, especially by HPLC, is a key screening method to avoid hemoglobinopathies in off springs. One important clinical condition which may lead to a wrong diagnosis of FMH’s is uncontrolled diabetes mellitus.

Multispecies study of patterns and drivers of wildlife impacts on human livelihoods in communal conservancies

AbstractFarmers in developing countries often work in challenging environments with poor infrastructure, marginal agricultural potential, and limited economic opportunities. These challenges are exacerbated when wildlife impact human livelihoods. Here, we analyze data quantifying the type and frequency of human‐wildlife impacts within communal conservancies across Namibia and explore possible drivers of temporal and spatial variation of these data. A total of 112,165 human‐wildlife impacts were reported between 2001 and 2019 at the national level, with livestock depredation the most common. Marked regional variation was however evident with crop raiding and attacks on humans more prevalent in the mesic North‐East, and both livestock depredation and infrastructure damage highest in the arid north‐western regions. Elephant, jackal, hyena, cheetah, and leopard (in descending order) were the species most frequently linked to reported damage. Distance to the nearest protected area and river, terrain ruggedness, conservancy size, and annual rainfall (amongst others) all had a significant impact on both the distribution and extent of human‐wildlife impact reports. Reports did not vary significantly with years but were significantly influenced by average monthly rainfall. Understanding spatial and temporal patterns of human‐wildlife impacts at a national scale, in addition to their potential drivers, allows for the identification of conflict hotspots and the allocation of resources and expertise to mitigate them. Ultimately, mitigating negative interactions between people and wildlife will allow for the continued sharing of space and with that the sustainability of a model that has seen a dramatic increase in both the distribution and abundance of wildlife in Namibia.

Availability of active therapeutic hypothermia at birth for neonatal hypoxic ischaemic encephalopathy: a UK population study from 2011 to 2018

ObjectiveTherapeutic hypothermia (TH) commenced soon after birth for neonatal hypoxic ischaemic encephalopathy (HIE) improves survival and reduces neurodisability. Availability of active TH at the place of birth (Immediate-TH) in the...

Regional variations and prevalence of psoriasis in Germany from 2010 to 2017: a cross-sectional, spatio-epidemiological study on ambulatory claims data

ObjectivesGlobal prevalence rates of psoriasis differ significantly, with lowest rates in the equator region and increasing tendencies towards the north but also differences within-country. Information on regional variations in Germany...

Australian surveys on parasite control in sheep between 2003 and 2019 reveal marked regional variation and increasing utilisation of online resources and on-farm biosecurity practices.

Australian Wool Innovation Limited (AWI) commissioned three cross-sectional surveys of sheep producers' sheep parasite control practices over a 15-year period from 2003 to 2018. The aims were to document current sheep parasite incidence and control practices, to measure change in sheep parasite control practices over time and to inform extension messages for sheep industry advisors and sheep farmers. The surveys were conducted in 2004, 2012 and 2019 measuring sheep parasite control practices in the years 2003, 2011 and 2018. The surveys focused on incidence and control of the three major sheep parasite groups; gastrointestinal nematodes, blowflies and lice. The 2003 and 2011 surveys were paper-based and the 2018 survey was accessed via a link to an online survey. This article is the first in a series of four presenting the results of the three surveys and will cover methods, demographics, production systems and general parasite management. Response rates to the surveys declined each year from the peak response rate in 2003 (n = 1365 in 2003; n = 575 in 2011 and n = 354 in 2018). Mean reported rainfall was significantly lower in 2018 (407 mm) than in 2003 (611 mm) and 2011 (650 mm). The demographics of the respondents and their production systems were largely similar between the three surveys for respondent age, median property size, income from wool and sheep meat, proportion of the property area cropped, median sheep dry sheep equivalent (DSEs), ewes as a proportion of the total flock and median cattle DSEs. Month of weaning was more likely to be in summer months for summer dominant rainfall areas and spring for intermediate and winter dominant rainfall areas. There was a marked increase in the proportion of respondents asking for an animal health history when introducing sheep to their flock from 2011 (9%) to 2018 (65%). Similarly, a greater proportion of respondents isolated introduced sheep for at least 2 weeks in 2018 (82%) compared with 2011 (19%). However, there was a decrease in the use of a quarantine lice treatment for introduced sheep from 2011 (50%) to 2018 (21%). Farmers rated themselves, other farmers or member of their staff as most important sources of information on parasite control in both 2011 and 2018. There was a significant increase in the proportion of respondents visiting the ParaBoss suite of websites from 2011 to 2018 confirming their growing importance for information delivery and decision support.

Levels and trends in Chagas disease-related mortality in Brazil, 2000–2019

Chagas disease remains an important public health problem with high morbidity and mortality in several Latin American countries. This nationwide population-based ecological study analyzes the epidemiological characteristics and time trends of Chagas disease-related mortality in Brazil, 2000–2019. We included all deaths reported in Brazil in which Chagas disease was mentioned in the death certificate either as an underlying or associated cause of death (multiple causes of death). Crude and age-adjusted mortality rates (per 100,000 inhabitants) were calculated and time trends analysis was performed using joinpoint regression models. In the study period, a total of 22,663,092 deaths were recorded in Brazil. Chagas disease was identified in 122,291 deaths (0.54%), 94.788 (77.5%) as an underlying cause and 27,503 (22.5%) as an associated cause. Average annual age-adjusted mortality rate was 3.22 deaths/100,000 inhabitants (95% confidence interval [CI]: 3.14-3.30). Chronic Chagas disease with cardiac involvement was the predominant clinical presentation mentioned. The highest mortality rates were observed in males, age group ≥80 years, black race/skin color, schooling 1-3 years of study, and residents in the Central-West region. Age-adjusted mortality rates showed a significant declining trend at the national level in the period (Average Annual Percent Change: -3.1%; 95% CI: -3.3; -3.0), with different local patterns and a more pronounced reduction in important endemic areas in the past. The findings show that, despite a consistent decline in mortality rates in Brazil over the study period, Chagas disease remains an important and neglected cause of death in the country, showing a marked regional variation that has social and health care implications. In addition to the control measures for disease transmission, it is necessary to guarantee access, coverage, and quality of health care to Chagas disease patients, seeking to prevent the occurrence of severe forms and deaths from the disease.

COVID-19 and plastic surgery: lessons from a national speciality review in the United Kingdom

BackgroundRamifications of coronavirus disease 2019 (COVID-19) on the re-structuring of healthcare are widespread, including delivery of surgical services across all specialties, including plastic surgery. Re-deployment of personnel and cessation of elective services are commonplace. However, there is a continued need for both emergency and oncological surgery. A national review of practice was conducted during the COVID-19 pandemic, to assess impact on services, staffing and training.MethodsKey aspects of current plastic surgery practice in the United Kingdom were examined in this cross-sectional study; operating capacity, location of theatre lists (national health service or outsourced private institutions (PIs)), differences across sub-specialties, change in anaesthesia practices, staffing, re-deployment, on-call provision and impact on training.ResultsThree-hundred and forty-four plastic surgeons in the United Kingdom provided practice data across 51 units. Theatre capacity and outpatient services were markedly reduced. Outsourcing of operating lists to PIs was widely utilised. Increased use of local anaesthetic hand procedures, the prioritisation of shorter operations with reduced microsurgery in both head and neck/lower limb and almost complete cessation of breast reconstruction were noted, together with marked regional variations. Re-deployment occurred at all staffing levels, whilst telemedicine played a critical role in both patient management and training.ConclusionsCOVID-19 has enforced unprecedented changes to surgical care delivery and training, as identified by examination of plastic surgery nationally in the United Kingdom. Novel means to support continued elective and emergency services, including oncology have been identified. Lessons learned will allow phased return of services and improved preparation for the future.

Factors associated with difficulty of hospital acceptance of patients suspected to have cerebrovascular diseases: A nationwide population-based observational study.

Although it is essential to shorten the interval to initial treatment in the care of acute ischemic stroke, some hospitals in Japan reject requests for hospital acceptance from on-scene emergency medical service personnel because of limited resources, which can cause delays in care. We aimed to assess the risk factors for difficulty of hospital acceptance of patients suspected to have cerebrovascular diseases. We conducted a retrospective analysis of the national ambulance records of the Fire and Disaster Management Agency in Japan in 2016. Multivariable logistic regression analysis was used to assess the association between difficulty of hospital acceptance of patients suspected to have cerebrovascular diseases and prehospital factors. During the study period, a total of 222,926 patients were included, and 5283 patients (2.4%) experienced difficulties in hospital acceptance. In multivariable analysis, nights (adjusted odds ratio [AOR] 1.54, 95% confidence interval [CI] 1.45-1.64), weekends (AOR 1.32, 95% CI 1.24-1.40), <25 percentile ratio of emergency physicians and neurosurgeons to all physicians (AOR 1.13, 95% CI 1.03-1.23) (AOR 1.36, 95% CI 1.25-1.48), and mean age of physicians (AOR 1.06, 95% CI 1.05-1.07) were significantly associated with difficulties of hospital acceptance of patients suspected to have cerebrovascular disease. There was a marked regional variation in the difficulties of hospital acceptance. Among the national ambulance records of patients suspected to have cerebrovascular diseases, certain prehospital factors such as weekends were positively associated with difficulty of hospital acceptance. A comprehensive strategy for hospital acceptance of patients with cerebrovascular diseases considering regional variation is required.

Sinus rhythm voltage fingerprinting in patients with mitral valve disease using a high-density epicardial mapping approach

AimsUnipolar voltage (UV) mapping is increasingly used for guiding ablative therapy of atrial fibrillation (AF) as unipolar electrograms (U-EGMs) are independent of electrode orientation and atrial wavefront direction. This study was aimed at constructing individual, high-resolution sinus rhythm (SR) UV fingerprints to identify low-voltage areas and study the effect of AF episodes in patients with mitral valve disease (MVD).Methods and resultsIntra-operative epicardial mapping (interelectrode distance 2 mm) of the right and left atrium, Bachmann’s bundle (BB), and pulmonary vein area was performed in 67 patients (27 male, 67 ± 11 years) with or without a history of paroxysmal AF (PAF). In all patients, there were considerable regional variations in voltages. UVs at BB were lower in patients with PAF compared with those without [no AF: 4.94 (3.56–5.98) mV, PAF: 3.30 (2.25–4.57) mV, P = 0.006]. A larger number of low-voltage potentials were recorded at BB in the PAF group [no AF: 2.13 (0.52–7.68) %, PAF: 12.86 (3.18–23.59) %, P = 0.001]. In addition, areas with low-voltage potentials were present in all patients, yet we did not find any predilection sites for low-voltage potentials to occur.ConclusionEven in SR, advanced atrial remodelling in MVD patients shows marked inter-individual and regional variation. Low UVs are even present during SR in patients without a history of AF indicating that low UVs should carefully be used as target sites for ablative therapy.

From initial segment to cauda: a regional characterization of mouse epididymal CD11c+ mononuclear phagocytes based on immune phenotype and function.

Successful sperm maturation and storage rely on a unique immunological balance that protects the male reproductive organs from invading pathogens and spermatozoa from a destructive autoimmune response. We previously characterized one subset of mononuclear phagocytes (MPs) in the murine epididymis, CX3CR1+ cells, emphasizing their different functional properties. This population partially overlaps with another subset of understudied heterogeneous MPs, the CD11c+ cells. In the present study, we analyzed the CD11c+ MPs for their immune phenotype, morphology, and antigen capturing and presenting abilities. Epididymides from CD11c-EYFP mice, which express enhanced yellow fluorescent protein (EYFP) in CD11c+ MPs, were divided into initial segment (IS), caput/corpus, and cauda regions. Flow cytometry analysis showed that CD11c+ MPs with a macrophage phenotype (CD64+ and F4/80+) were the most abundant in the IS, whereas those with a dendritic cell signature [CD64- major histocompatibility complex class II (MHCII)+] were more frequent in the cauda. Immunofluorescence revealed morphological and phenotypic differences between CD11c+ MPs in the regions examined. To assess the ability of CD11c+ cells to take up antigens, CD11c-EYFP mice were injected intravenously with ovalbumin. In the IS, MPs expressing macrophage markers were most active in taking up the antigens. A functional antigen-presenting coculture study was performed, whereby CD4+ T cells were activated after ovalbumin presentation by CD11c+ epididymal MPs. The results demonstrated that CD11c+ MPs in all regions were capable of capturing and presenting antigens. Together, this study defines a marked regional variation in epididymal antigen-presenting cells that could help us understand fertility and contraception but also has larger implications in inflammation and disease pathology.

Clinical presentation, management, and 6-month outcomes in women with peripartum cardiomyopathy: an ESC EORP registry.

We sought to describe the clinical presentation, management, and 6-month outcomes in women with peripartum cardiomyopathy (PPCM) globally. In 2011, >100 national and affiliated member cardiac societies of the European Society of Cardiology (ESC) were contacted to contribute to a global registry on PPCM, under the auspices of the ESC EURObservational Research Programme. These societies were tasked with identifying centres who could participate in this registry. In low-income countries, e.g. Mozambique or Burkina Faso, where there are no national societies due to a shortage of cardiologists, we identified potential participants through abstracts and publications and encouraged participation into the study. Seven hundred and thirty-nine women were enrolled in 49 countries in Europe (33%), Africa (29%), Asia-Pacific (15%), and the Middle East (22%). Mean age was 31 ± 6 years, mean left ventricular ejection fraction (LVEF) was 31 ± 10%, and 10% had a previous pregnancy complicated by PPCM. Symptom-onset occurred most often within 1 month of delivery (44%). At diagnosis, 67% of patients had severe (NYHA III/IV) symptoms and 67% had a LVEF ≤35%. Fifteen percent received bromocriptine with significant regional variation (Europe 15%, Africa 26%, Asia-Pacific 8%, the Middle East 4%, P < 0.001). Follow-up was available for 598 (81%) women. Six-month mortality was 6% overall, lowest in Europe (4%), and highest in the Middle East (10%). Most deaths were due to heart failure (42%) or sudden (30%). Re-admission for any reason occurred in 10% (with just over half of these for heart failure) and thromboembolic events in 7%. Myocardial recovery (LVEF > 50%) occurred only in 46%, most commonly in Asia-Pacific (62%), and least commonly in the Middle East (25%). Neonatal death occurred in 5% with marked regional variation (Europe 2%, the Middle East 9%). Peripartum cardiomyopathy is a global disease, but clinical presentation and outcomes vary by region. Just under half of women experience myocardial recovery. Peripartum cardiomyopathy is a disease with substantial maternal and neonatal morbidity and mortality.