Evaluating Natural History and Follow Up Strategies for Non-obstructive Urolithiasis in Pediatric Population

Objective: While small non-obstructive stones in the adult population are usually observed with minimal follow-up, the same guidelines for management in the pediatric population have not been well-studied. We evaluate the clinical outcomes of small non-obstructing kidney stones in the pediatric population to better define the natural history of the disease.Methods: In this IRB-approved retrospective study, patients with a diagnosis of kidney stones from January 2011 to March 2017 were identified using ICD9 and ICD10 codes. Patients with ureteral stones, obstruction, or stones >5 mm in size were excluded. Patients with no follow-up after initial imaging were also excluded. Patients with a history of stones or prior stone interventions were included in our population. Frequency of follow-up ultrasounds while on observation were noted and any ER visits, stone passage episodes, infections, and surgical interventions were documented.Results: Over the 6-year study period, 106 patients with non-obstructing kidney stones were identified. The average age at diagnosis was 12.5 years and the average stone size was 3.6 mm. Average follow-up was 17 months. About half of the patients had spontaneous passage of stones (54/106) at an average time of 13 months after diagnosis. Stone location did not correlate with spontaneous passage rates. Only 6/106 (5.7%) patients required stone surgery with ureteroscopy and/or PCNL at an average time of 12 months after initial diagnosis. The indication for surgery in all 6 cases was pain. 17/106 (16%) patients developed febrile UTIs and a total of 43 ER visits for stone-related issues were noted, but no patients required urgent intervention for an infected obstructing stone. Median interval for follow-up was every 6 months with renal ultrasounds, which then was prolonged to annual follow up in most cases.Conclusions: The observation of pediatric patients with small non-obstructing stones is safe with no episodes of acute obstructive pyelonephritis occurring in these patients. The sole indication for intervention in our patient population was pain, which suggests that routine follow-up ultrasounds may not be necessary for the follow-up of pediatric non-obstructive renal stones ≤5 mm in size

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma

Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferation defects that arise from nucleotide depletion. Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to inhibit elongation at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic RNAs to bind to and be stabilized by HEXIM1. HEXIM1 plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals an important role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma

Alcohol, tobacco and illicit drug use amongst same-sex attracted women: results from the Western Australian Lesbian and Bisexual Women's Health and Well-Being Survey

Background: The prevalence of alcohol, tobacco and illicit drug use has been reported to be higheramongst lesbian and bisexual women (LBW) than their heterosexual counterparts. However, few studieshave been conducted with this population in Australia and rates that have been reported vary considerably.Methods: A self-completed questionnaire exploring a range of health issues was administered to 917women aged 15-65 years (median 34 years) living in Western Australia, who identified as lesbian orbisexual, or reported having sex with another woman. Participants were recruited from a range of settings,including Perth Pride Festival events (67.0%, n = 615), online (13.2%, n = 121), at gay bars and nightclubs(12.9%, n = 118), and through community groups (6.9%, n = 63). Results were compared against availablestate and national surveillance data.Results: LBW reported consuming alcohol more frequently and in greater quantities than women in thegeneral population. A quarter of LBW (25.7%, n = 236) exceeded national alcohol guidelines by consumingmore than four standard drinks on a single occasion, once a week or more. However, only 6.8% (n = 62)described themselves as a heavy drinker, suggesting that exceeding national alcohol guidelines may be anormalised behaviour amongst LBW. Of the 876 women who provided data on tobacco use, 28.1% (n =246) were smokers, nearly double the rate in the female population as a whole. One third of the sample(33.6%, n = 308) reported use of an illicit drug in the previous six months. The illicit drugs most commonlyreported were cannabis (26.4%, n = 242), meth/amphetamine (18.6%, n = 171), and ecstasy (17.9%, n =164). Injecting drug use was reported by 3.5% (n = 32) of participants.Conclusion: LBW appear to use alcohol, tobacco and illicit drugs at higher rates than women generally,indicating that mainstream health promotion messages are not reaching this group or are not perceivedas relevant. There is an urgent need for public health practitioners working in the area of substance useto recognise that drug consumption and use patterns of LBW are likely to be different to the widerpopulation and that special considerations and strategies are required to address the unique and complexneeds of this population

Vesicoamniotic Shunting Improves Outcomes in a Subset of Prune Belly Syndrome Patients at a Single Tertiary Center

Objective: Review outcomes of Prune Belly Syndrome (PBS) with the hypothesis that contemporary management improves mortality.Methods: A retrospective chart review of inpatient and outpatient PBS patients referred between 2000 and 2018 was conducted to assess outcomes at our institution. Data collected included age at diagnosis, concomitant medical conditions, imaging, operative management, length of follow-up, and renal function.Results: Forty-five PBS patients presented during these 18 years. Prenatal diagnoses were made in 17 (39%); 65% of these patients underwent prenatal intervention. The remaining patients were diagnosed in the infant period (20, 44%) or after 1 year of age (8, 18%). Twelve patients died from cardiopulmonary complications in the neonatal period; the neonatal mortality rate was 27%. The mean follow-up among patients surviving the neonatal period was 84 months. Forty-two patients had at least one renal ultrasound (RUS); of the 30 patients with NICU RUSs, 26 (89%) had hydronephrosis and/or ureterectasis. Of the 39 patients who underwent voiding cystourethrogram (VCUG), 28 (62%) demonstrated VUR. Fifty-nine percent had respiratory distress. Nine patients (20%) were oxygen-dependent by completion of follow up. Thirty-eight patients (84%) had other congenital malformations including genitourinary (GU) 67%, gastrointestinal (GI) 52%, and cardiac 48%. Sixteen patients (36%) had chronic kidney disease (CKD) of at least stage 3; three patients (7%) had received renal transplants. Eighty-four percent of patients had at least one surgery (mean 3.4, range 0–6). The most common was orchiopexy (71%). The next most common surgeries were vesicostomy (39%), ureteral reimplants (32%), abdominoplasty (29%), nephrectomy (25%), and appendicovesicostomy (21%). After stratifying patients according to Woodard classification, a trend for 12% improvement in mortality after VAS was noted in the Woodard Classification 1 cohort.Conclusions: PBS patients frequently have multiple congenital anomalies. Pulmonary complications are prevalent in the neonate while CKD (36%) is prevalent during late childhood. The risk of CKD increased significantly with the presence of other congenital anomalies in our cohort. Mortality in childhood is most common in infancy and may be as low as 27%. Contemporary management of PBS, including prenatal interventions, reduced the neonatal mortality rate in a subset of our cohort

Changing outcomes following pelvic exenteration for locally advanced and recurrent rectal cancer

Background Pelvic exenteration for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) is technically challenging but increasingly performed in specialist centres. The aim of this study was to compare outcomes of exenteration over time. Methods This was a multicentre retrospective study of patients who underwent exenteration for LARC and LRRC between 2004 and 2015. Surgical outcomes, including rate of bone resection, flap reconstruction, margin status and transfusion rates, were examined. Outcomes between higher- and lower-volume centres were also evaluated. Results Some 2472 patients underwent pelvic exenteration for LARC and LRRC across 26 institutions. For LARC, rates of bone resection or flap reconstruction increased from 2004 to 2015, from 3.5 to 12.8 per cent, and from 12.0 to 29.4 per cent respectively. Fewer units of intraoperative blood were transfused over this interval (median 4 to 2 units; P = 0.040). Subgroup analysis showed that bone resection and flap reconstruction rates increased in lower- and higher-volume centres. R0 resection rates significantly increased in low-volume centres but not in high-volume centres over time (low-volume: from 62.5 to 80.0 per cent, P = 0.001; high-volume: from 83.5 to 88.4 per cent, P = 0.660). For LRRC, no significant trends over time were observed for bone resection or flap reconstruction rates. The median number of units of intraoperative blood transfused decreased from 5 to 2.5 units (P < 0.001). R0 resection rates did not increase in either low-volume (from 51.7 to 60.4 per cent; P = 0.610) or higher-volume (from 48.6 to 65.5 per cent; P = 0.100) centres. No significant differences in length of hospital stay, 30-day complication, reintervention or mortality rates were observed over time. Conclusion Radical resection, bone resection and flap reconstruction rates were performed more frequently over time, while transfusion requirements decreased

Endothelial Dysfunction and Specific Inflammation in Obesity Hypoventilation Syndrome

BACKGROUND: Obesity hypoventilation syndrome (OHS) is associated with increased cardiovascular morbidity. What moderate chronic hypoventilation adds to obesity on systemic inflammation and endothelial dysfunction remains unknown. QUESTION: To compare inflammatory status and endothelial function in OHS versus eucapnic obese patients. METHODOLOGY: 14 OHS and 39 eucapnic obese patients matched for BMI and age were compared. Diurnal blood gazes, overnight polysomnography and endothelial function, measured by reactive hyperemia peripheral arterial tonometry (RH-PAT), were assessed. Inflammatory (Leptin, RANTES, MCP-1, IL-6, IL-8, TNFalpha, Resistin) and anti-inflammatory (adiponectin, IL-1Ra) cytokines were measured by multiplex beads immunoassays. PRINCIPAL FINDINGS: OHS exhibited a higher PaCO(2), a lower forced vital capacity (FVC) and tended to have a lower PaO(2) than eucapnic obese patients. (HS)-CRP, RANTES levels and glycated haemoglobin (HbA1c) were significantly increased in OHS (respectively 11.1+/-10.9 vs. 5.7+/-5.5 mg x l(-1) for (HS)-CRP, 55.9+/-55.3 vs 23.3+/-15.8 ng/ml for RANTES and 7.3+/-4.3 vs 6.1+/-1.7 for HbA1c). Serum adiponectin was reduced in OHS (7606+/-2977 vs 13,660+/-7854 ng/ml). Endothelial function was significantly more impaired in OHS (RH-PAT index: 0.22+/-0.06 vs 0.51+/-0.11). CONCLUSIONS: Compared to eucapnic obesity, OHS is associated with a specific increase in the pro-atherosclerotic RANTES chemokine, a decrease in the anti-inflammatory adipokine adiponectin and impaired endothelial function. These three conditions are known to be strongly associated with an increased cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT00603096

Multi-decadal changes in tundra environments and ecosystems: Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF).

Understanding the responses of tundra systems to global change has global implications. Most tundra regions lack sustained environmental monitoring and one of the only ways to document multi-decadal change is to resample historic research sites. The International Polar Year (IPY) provided a unique opportunity for such research through the Back to the Future (BTF) project (IPY project #512). This article synthesizes the results from 13 papers within this Ambio Special Issue. Abiotic changes include glacial recession in the Altai Mountains, Russia; increased snow depth and hardness, permafrost warming, and increased growing season length in sub-arctic Sweden; drying of ponds in Greenland; increased nutrient availability in Alaskan tundra ponds, and warming at most locations studied. Biotic changes ranged from relatively minor plant community change at two sites in Greenland to moderate change in the Yukon, and to dramatic increases in shrub and tree density on Herschel Island, and in sub-arctic Sweden. The population of geese tripled at one site in northeast Greenland where biomass in non-grazed plots doubled. A model parameterized using results from a BTF study forecasts substantial declines in all snowbeds and increases in shrub tundra on Niwot Ridge, Colorado over the next century. In general, results support and provide improved capacities for validating experimental manipulation, remote sensing, and modeling studies

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Comparative molecular biological analysis of membrane transport genes in organisms

Comparative analyses of membrane transport genes revealed many differences in the features of transport homeostasis in eight diverse organisms, ranging from bacteria to animals and plants. In bacteria, membrane-transport systems depend mainly on single genes encoding proteins involved in an ATP-dependent pump and secondary transport proteins that use H+ as a co-transport molecule. Animals are especially divergent in their channel genes, and plants have larger numbers of P-type ATPase and secondary active transporters than do other organisms. The secondary transporter genes have diverged evolutionarily in both animals and plants for different co-transporter molecules. Animals use Na+ ions for the formation of concentration gradients across plasma membranes, dependent on secondary active transporters and on membrane voltages that in turn are dependent on ion transport regulation systems. Plants use H+ ions pooled in vacuoles and the apoplast to transport various substances; these proton gradients are also dependent on secondary active transporters. We also compared the numbers of membrane transporter genes in Arabidopsis and rice. Although many transporter genes are similar in these plants, Arabidopsis has a more diverse array of genes for multi-efflux transport and for response to stress signals, and rice has more secondary transporter genes for carbohydrate and nutrient transport