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Submarine groundwater discharge (SGD) is an important phenomenon that governs hydrological cycles at the land‐to‐ocean transition zone. SGD manifests as cold and buoyant freshwaters influx from the seafloor to the water column that contains carbon, nutrients, metals, and greenhouse gases, altering coastal areas' oceanographical and biochemical properties. Here, we present electromagnetic imaging of large‐scale freshwater plumes in high‐resolution, offshore west Hawai'i. Electrical resistivity models detect multiple vertical freshwater plumes extending from the seafloor to the ocean surface. Additionally, our models image extensive spatially distributed surface freshwater. The resistivity of these plumes and surface freshwater ranges from ∼1 to 30 Ωm. Resistivity‐to‐salinity calculation indicates a plume‐scale salinity range of ∼0.3–9.9, containing up to 87% of freshwater. Our results imply that substantial volumes of freshwater occupy water column plumes in Hawai'i. This study offers a new and effective method to elucidate hydrogeologic and ocean processes affecting biogeochemical cycles in coastal waters worldwide. Plain Language Summary: Submarine groundwater discharge (SGD) is a flow of cold and buoyant freshwater from the seafloor to the ocean surface. Because SGD contains carbon, nutrients, metals, and greenhouse gases, it changes coastal waters' oceanographical and biochemical properties. Therefore, SGD is an important phenomenon that governs hydrological cycles at the land‐to‐ocean transition zone. Due to the high spatial distribution and variability of SGD at the ocean surface, it is nontrivial to map SGD seep location and fluxes using traditional oceanographic methods. Here, we present electromagnetic imaging of large‐scale freshwater plumes in high‐resolution, offshore west Hawai'i. Our electrical resistivity models detect multiple vertical freshwater plumes (SGD point‐sources) as well as spatially distributed surface freshwater, extending to a distance of ∼3 km offshore Hawai'i. Plume‐scale salinity distribution indicates that these plumes contain up to 87% of freshwater. Thus, a substantial volume of freshwater occupies Hawaiian water column plumes. This is the first study to demonstrate the marine electromagnetic method's capability to image and delineate freshwater plumes from the seafloor to the ocean surface. We offer a new and effective method to elucidate hydrogeologic and ocean processes that affect biogeochemical cycles in coastal waters worldwide. Key Points: Surface‐towed marine‐controlled source electromagnetic technique is capable of imaging freshwater plumes in high‐resolutionMultiple large‐scale freshwater plumes and surface freshwater bodies were detected offshore the island of Hawai'iSubstantial volumes of freshwater occupy seafloor to ocean surface plumes in west Hawai'i [ABSTRACT FROM AUTHOR]

Background: Chronic left bundle branch block (LBBB) can lead to LBBB‐mediated cardiomyopathy from left ventricular dysynchrony. His‐bundle pacing (HBP) results in direct electrical synchrony using the native His‐Purkinje system, providing a novel treatment for this cardiomyopathy. Objective: To assess the feasibility of HBP for cardiac resynchronization therapy (CRT) in LBBB‐mediated cardiomyopathy patients. Methods: Retrospective database review was conducted on patients who underwent CRT by the HBP capable provider at Indiana University Health and Eskenazi Hospital from August 2015 to August 2017. A subset of patients who met the predefined syndrome criteria of LBBB‐mediated cardiomyopathy who underwent HBP were identified. Clinical, echocardiographic, and electrocardiographic variables were extracted at baseline and follow‐up. Results: Nine patients had cardiomyopathy and LBBB. Among those two were lost to follow‐up. Seven patients were included in the analysis. The average time from device implantation to the last follow‐up was 14.5 months. Left ventricular ejection fraction improved on average from 25% to 50% (p =.0001). The left ventricular end‐systolic dimension decreased from 47 to 37 mm (p =.003) and the left ventricular end‐diastolic dimension decreased from 55 to 48 mm (p =.03). QRS duration with HBP‐CRT decreased from 152 to 115 ms. New York Heart Association classification improved from an average of 2.7–2. Conclusion: HBP is a viable technique for pursuing CRT in patients with LBBB‐mediated cardiomyopathy. [ABSTRACT FROM AUTHOR]

Climate change manifestation in the ocean, through warming, oxygen loss, increasing acidification, and changing particulate organic carbon flux (one metric of altered food supply), is projected to affect most deep‐ocean ecosystems concomitantly with increasing direct human disturbance. Climate drivers will alter deep‐sea biodiversity and associated ecosystem services, and may interact with disturbance from resource extraction activities or even climate geoengineering. We suggest that to ensure the effective management of increasing use of the deep ocean (e.g., for bottom fishing, oil and gas extraction, and deep‐seabed mining), environmental management and developing regulations must consider climate change. Strategic planning, impact assessment and monitoring, spatial management, application of the precautionary approach, and full‐cost accounting of extraction activities should embrace climate consciousness. Coupled climate and biological modeling approaches applied in the water and on the seafloor can help accomplish this goal. For example, Earth‐System Model projections of climate‐change parameters at the seafloor reveal heterogeneity in projected climate hazard and time of emergence (beyond natural variability) in regions targeted for deep‐seabed mining. Models that combine climate‐induced changes in ocean circulation with particle tracking predict altered transport of early life stages (larvae) under climate change. Habitat suitability models can help assess the consequences of altered larval dispersal, predict climate refugia, and identify vulnerable regions for multiple species under climate change. Engaging the deep observing community can support the necessary data provisioning to mainstream climate into the development of environmental management plans. To illustrate this approach, we focus on deep‐seabed mining and the International Seabed Authority, whose mandates include regulation of all mineral‐related activities in international waters and protecting the marine environment from the harmful effects of mining. However, achieving deep‐ocean sustainability under the UN Sustainable Development Goals will require integration of climate consideration across all policy sectors. [ABSTRACT FROM AUTHOR]

Abstract: We describe three cases of hair loss in a female pattern hair loss (FPHL) distribution with histologic features of lichen planopilaris (LPP). All patients had a history of diffuse, gradual hair loss in a Christmas tree pattern that clinically presented as FPHL on gross and dermoscopic examination. Notably, there were no characteristic clinical signs of LPP and no histologic features of FPHL. These cases are most consistent with cicatricial pattern hair loss (CPHL). This relatively new entity is similar to fibrosing alopecia in a pattern distribution (FAPD) in that they are both scarring alopecias confined to a FPHL distribution, but CPHL lacks the clinical signs of perifollicular erythema and perifollicular keratosis seen in FAPD. These three cases may present an early, subtle form of CPHL and will be of interest to clinicians and histopathologists alike. [ABSTRACT FROM AUTHOR]

Background and Purpose: Neurons derived from mouse embryonic stem cells (mESCs) are a valuable resource for basic pharmacological research. With the exception of cardiomyocytes, there is relatively little understanding of the pharmacology of stem cell-derived differentiated cells. In this study we investigate P2 receptor agonist effects on GABAergic neurons derived from mESCs.Experimental Approach: mESCs were differentiated into GABAergic neurons in the presence of N2B27 culture medium. At day 24 of differentiation GABAergic neuronal responsiveness to purinergic agonists was investigated using calcium imaging and [3H]-GABA release studies.Key Results: Sub-populations of GABAergic neurons responded to some or all of the adenine and uracil nucleotides ATP, ADP, UTP and UDP (all 100 microM) with elevations of intracellular Ca2+ ([Ca2+]i). The number of neurons responding to ATP was reduced by suramin (100 microM), PPADS (10 microM) and MRS2179 (10 microM), but not by NF023 (10 microM). The response to ATP was modulated by extracellular Zn2+ and pH. Neurons also responded to ATP (100 microM) with the release of [3H]-GABA, an effect completely inhibited by tetrodotoxin (100 nM). Ap4A and 2-methylthioATP both elicited significant [3H]-GABA release. Reverse transcriptase PCR showed the presence of P2X1,2,3,4,5,6 and P2X7, and P2Y1,2 and P2Y6 receptors. mESCs expressed P2X2,5 and P2X7 and P2Y1,2 and P2Y6 receptors.Conclusions and Implications: GABAergic neurons derived from stem cells elevate [Ca2+]i predominantly via the activation of P2X2, P2X4 and P2Y1 receptors. This study shows that mESCs generate good models of neuronal function for in vitro pharmacological investigation. [ABSTRACT FROM AUTHOR]

Background: In the current study, the authors present a comprehensive genomic profile (CGP)-based study of advanced urothelial carcinoma (UC) designed to detect clinically relevant genomic alterations (CRGAs).Methods: DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections from 295 consecutive cases of recurrent/metastatic UC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 688X for all coding exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer, using process-matched normal control samples as a reference. CRGAs were defined as GAs linked to drugs on the market or currently under evaluation in mechanism-driven clinical trials.Results: All 295 patients assessed were classified with high-grade (International Society of Urological Pathology classification) and advanced stage (stage III/IV American Joint Committee on Cancer) disease, and 294 of 295 patients (99.7%) had at least 1 GA on CGP with a mean of 6.4 GAs per UC (61% substitutions/insertions/deletions, 37% copy number alterations, and 2% fusions). Furthermore, 275 patients (93%) had at least 1 CRGA involving 75 individual genes with a mean of 2.6 CRGAs per UC. The most common CRGAs involved cyclin-dependent kinase inhibitor 2A (CDKN2A) (34%), fibroblast growth factor receptor 3 (FGFR3) (21%), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (20%), and ERBB2 (17%). FGFR3 GAs were diverse types and included 10% fusions. ERBB2 GAs were equally divided between amplifications and substitutions. ERBB2 substitutions were predominantly within the extracellular domain and were highly enriched in patients with micropapillary UC (38% of 32 cases vs 5% of 263 nonmicropapillary UC cases; P<.0001).Conclusions: Using a CGP assay capable of detecting all classes of GA simultaneously, an extraordinarily high frequency of CRGA was identified in a large series of patients with advanced UC. Cancer 2016;122:702-711. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article presents a study on the genomic features in adolescent and young adults and clinical outcome for non-Hodgkin lymphoma (NHL). Topics include the difference of the clinical outcome of NHL between younger and older populations, potential therapeutic targets specific for younger population, and age-related genomic profiles of NHL. Alterations in histone modification genes are discussed.

ABSTRACT The problem of arsenic-contaminated groundwater in Cambodia came to light relatively recently as compared with Bangladesh and surrounding areas, but 12 years on, not enough has been done in terms of awareness raising at the national level. Arsenic levels in some Cambodian well waters are comparable with those in some of the world's worst-impacted areas and awareness raising is a matter of urgency. This paper examines the impact of one awareness-raising initiative by a nongovernmental organisation (Resources Development International, RDI) by comparing knowledge levels in 'mitigation' and 'comparison' (control) villages. Socio-economic correlates of arsenic knowledge were analysed, and the effect of knowledge on water consumption behaviour was also explored. A structured questionnaire survey was undertaken in three villages with a total of 407 respondents. Findings suggest that in Cambodia, knowledge of the problem does not appear to be gendered, as has been reported in other countries, but wealth and education levels do impact upon knowledge where there have not been awareness-raising activities. As RDI focused their efforts on the most intensively affected area, it is difficult to separate out the effects of their awareness raising with 'word of mouth' and proximity to a high-risk area. The awareness-raising programme does appear, however, to have ironed out the effect of education and wealth on arsenic knowledge but may have bypassed the more elderly. Knowledge of the problem generates a greater change in water consumption behaviour than has been reported elsewhere. Overall, knowledge of the problem remains very low. Copyright © 2013 John Wiley & Sons, Ltd. Key messages Significant differences exist between socio-economic factors affecting knowledge of the arsenic problem in Cambodia as compared with areas where comparative studies have been undertaken, such as Bangladesh., The awareness-raising efforts of a nongovernmental organisation have significantly improved knowledge and ironed out the effects of socio-economic factors affecting knowledge (education and wealth)., Knowledge of the arsenic problem remains low, but awareness of the issue generates a greater change in water consumption behaviour than has been found elsewhere. [ABSTRACT FROM AUTHOR]

This paper presents a novel design of single-pole four-throw (SP4T) RF-MEMS switch employing both capacitive and ohmic switches. It is designed on high-resistivity silicon substrate and has a compact area of 1.06mm2. The series or ohmic switches have been designed to provide low insertion loss with good ohmic contact. The pull-in voltage for ohmic switches is calculated to be 7.19V. Shunt or capacitive switches have been used in each port to improve the isolation for higher frequencies.The proposed SP4T switch provides excellent RF performances with isolation better than 70.64 dB and insertion loss less than 0.72 dB for X-band between the input port and each output port. [ABSTRACT FROM AUTHOR]

Medical Education 2011: : 712-721 Being a good doctor requires competency in ethics. Accordingly, ethics education during residency training is important. We studied the everyday ethics-related issues (i.e. ordinary ethics issues commonly faced) that internal medical residents encounter in their out-patient clinic and determined whether teaching about these issues occurred during faculty preceptor-resident interactions. This study involved a multi-method qualitative research design combining observation of preceptor-resident discussions with preceptor interviews. The study was conducted in two different internal medicine training programme clinics over a 2-week period in June 2007. Fifty-three residents and 19 preceptors were observed, and 10 preceptors were interviewed. Transcripts of observer field notes and faculty interviews were carefully analysed. The analysis identified several themes of everyday ethics issues and determined whether preceptors identified and taught about these issues. Everyday ethics content was considered present in 109 (81%) of the 135 observed case presentations. Three major thematic domains and associated sub-themes related to everyday ethics issues were identified, concerning: (i) the Doctor-Patient Interaction (relationships; communication; shared decision making); (ii) the Resident as Learner (developmental issues; challenges and conflicts associated with training; relationships with colleagues and mentors; interactions with the preceptor), and; (iii) the Doctor-System Interaction (financial issues; doctor-system issues; external influences; doctor frustration related to system issues). Everyday ethics issues were explicitly identified by preceptors (without teaching) in 18 of 109 cases (17%); explicit identification and teaching occurred in only 13 cases (12%). In this study a variety of everyday ethics issues were frequently encountered as residents cared for patients. Yet, faculty preceptors infrequently explicitly identified or taught these issues during their interactions with residents. Ethics education is important and residents may regard teaching about the ethics-related issues they actually encounter to be highly relevant. A better understanding of the barriers to teaching is needed in order to promote education about everyday ethics in the out-patient setting. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine if, following vasectomy, epididymal obstruction resulted in changes in vasal stump fluid using a rat vasectomy model. One hundred and twenty-two mature male rats underwent bilateral surgical vasectomy and subsequent unilateral epididymal obstruction. Animals were randomly assigned to one of the five cohorts, which determined the time to kill and vasal fluid assessment. Numbers of whole sperm and sperm heads were compared between the obstructed and non-obstructed sides. Parametric analysis of microscopic vasal fluid findings was performed using a paired t-test. Whole sperm and sperm heads were detected bilaterally among the initial five cohorts. On the obstructed epididymis side, percentage of whole sperm dropped from 36.9% to less than 1% and sperm heads increased from 63.2 to 99.7% at 12 weeks post-obstruction ( p < 0.05 at each time interval). On the unobstructed side, percentage of whole sperm rose from 66.3 to 89.5% and sperm heads dropped from 33.7 to 10.5% ( p < 0.05 at each time interval). At 12 weeks, the difference between the obstructed and non-obstructed sides for both percentage and quantity of whole sperm and heads was significant with a p value of <0.001. In this rat model, following vasectomy and subsequent epididymal obstruction, testicular vasal stump fluid will contain progressively diminishing numbers of whole sperm and increases in the percentage and absolute numbers of sperm heads. [ABSTRACT FROM AUTHOR]

Associate Editor Ash Tewari Editorial Board Ralph Clayman, USA Inderbir Gill, USA Roger Kirby, UK Mani Menon, USA OBJECTIVE To determine if obesity is associated with prolonged surgery or more complications during and after surgery in patients undergoing robot-assisted laparoscopic prostatectomy (RALP). PATIENTS AND METHODS Between December 2003 and September 2005 data were collected prospectively for all patients undergoing RALP. Obesity was defined as a body mass index of ≥ 30 kg/m2. The duration of surgery was recorded, determining the duration of steps, including overall, robotic assistance, and vesico-urethral anastomosis. In all, 285 patients had RALP by one of two surgeons; 236 were classified as not obese and 49 as obese. RESULTS The characteristics of the two groups were similar before and after RALP (mean age 60.7 vs 60.3 years, prostate-specific antigen level 7.9 vs 7.9 ng/mL, prostate weight 47.3 vs 45.3 g, length of stay 3.2 vs 3.5 days, and indwelling catheterization 8.3 vs 7.9 days). The mean duration of surgical steps was less for the non-obese than the obese group, with urethral dissection requiring 16 vs 19.3 min ( P < 0.05), anastomotic time 30 vs 36 min ( P < 0.01), and port closure 11 vs 14.5 min ( P < 0.001), but the total duration of surgery, at 190 vs 205 min, was not significantly different ( P = 0.07). In the non-obese group there were seven (3%) prolonged drain tube leaks, vs four (8%) in the obese group ( P = 0.08). CONCLUSIONS Obesity was associated with longer anastomotic times, but the overall duration was similar. Overall complication rates were not significantly different. The continuing follow-up will determine if obesity predisposes patients to greater long-term morbidity after RALP. [ABSTRACT FROM AUTHOR]

Coronary artery disease accounts for significant morbidity and mortality in patients with chronic kidney disease (CKD). Besides the higher prevalence of traditional risk factors, several uremia-related factors may play a role in accelerated atherosclerosis, such as elevated levels of lipoprotein (a) (Lp(a)). The effect of maintenance hemodialysis (MHD) on Lp(a) levels is not well understood. The present work was carried out to study the Lp(a) levels in Stage 4 and Stage 5 CKD patients as well as the effect of MHD on Lp(a) levels in patients with Stage 5 CKD. The study subjects included 15 patients with Stage 4 CKD, 15 patients with Stage 5 CKD, and 15 age- and sex-matched healthy controls. Plasma Lp(a) was measured by ELISA in all the subjects at the time of entry into the study and after 4 weeks of MHD in patients with Stage 5 CKD. Patients on MHD were dialyzed two to three times weekly for 4 hr during each session. Mean Lp(a) levels were significantly higher in patients with CKD than in control patients. In patients with Stage 4 CKD, the Lp(a) level was 34.0 ± 19.5 mg/dL, whereas in Stage 5 CKD the level was 49.0 ± 30.9 and in healthy controls it was 22.2 ± 16.4. In patients with Stage 5 CKD, 4 weeks of MHD led to a significant fall in Lp(a) levels by 23.6% (P < 0.001). The results of this study show that increases in Lp(a) levels start early during the course of CKD and become more pronounced with increased severity of disease. Initiation of MHD lowers Lp(a) levels and may have a long-term beneficial effect on cardiovascular morbidity and mortality. [ABSTRACT FROM AUTHOR]

Summary objective Pituitary tumour transforming gene (PTTG) encodes a multifunctional protein that is implicated in initiating and perpetuating pituitary adenoma growth. PTTG appears to have key regulatory functions in determining control of many fundamental cellular events including mitosis, cell transformation, DNA repair and gene regulation. Several of these events are mediated through interactions with PTTG binding factor (PBF) and fibroblast growth factor-2 (FGF-2). Given this background, we have determined the expression of PTTG, PBF, FGF-2 and its receptor FGF-R-1 in a large cohort of pituitary adenomas and have sought associations between levels of gene expression and clinical markers of tumour behaviour. patients and methods We used real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses to measure PTTG, PBF, FGF-2 and FGF-R-1 expression in ex vivo pituitary tumours (N = 121). Clinical data, including accurate radiological assessment of tumour characteristics, were used to determine any associations between gene expression and tumour behaviour. results PTTG was increased significantly (fivefold, P = 0·005) in adenomas compared with normal pituitaries. We also demonstrated that PBF was similarly raised in adenomas (sixfold, P = 0·0001), and was significantly correlated with PTTG expression. FGF-2 and its receptor FGF-R-1 were also raised in adenomas compared with normal pituitary tissue. Moreover, significantly enhanced expression of FGF-R-1 was observed in invasive adenomas compared with other pituitary tumours. conclusions Our data support a fundamental role for PTTG-mediated upregulation of FGF-2 signalling in pituitary tumorigenesis and growth, and suggest that receptor-mediated mechanisms of growth factor action may be critically important. Further prospective studies are required to determine whether measurement of FGF-R-1 mRNA will be of clinical use as a prognostic marker in patients with pituitary... [ABSTRACT FROM AUTHOR]

SUMMARY A 20-year-old female with cystic fibrosis presented with a white marginal palmar eruption after exposure to water. There was no family history of keratoderma. A biopsy showed hyperkeratosis around dilated eccrine ostia. These features are similar to a recently described condition, transient reactive papulotranslucent acrokeratoderma. This is thought to be a variant of hereditary papulotranslucent acrokeratoderma, one of the punctate keratodermas. Association with cystic fibrosis has not been described previously. [ABSTRACT FROM AUTHOR]

The article reports on the study that examines a patient who underwent living-related renal transplantation. It shows that an interaction between tacrolimus and amlodipine may lead to galactorrhoea and mastalgia. It suggests that an awareness of the potential interaction may avoid expensive and elaborate laboratory investigation in renal transplant recipients.

The article presents a case study of a 52-year old man with asymptomatic lesion on the right foot. The patient underwent an examination, and it found out that he developed a disease called tuberculosis verrucosa cutis (TBCV). It also discusses the transplantation the patient passed through which causes for the development of the disease, and gives a little background about TBVC.

A letter to the editor discussing a case of contralateral adrenal metastasis from renal cell carcinoma is presented.

A. Gupta, A. Khaira. Opportunistic non-BK viral disease after renal transplantation: a game of numbers Transpl Infect Dis 2011: 329-330. All rights reserved [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Pedal Oedema: A Rare Side-Effect of Faropenem" in the previous issue.