Patterns of lymph node sampling and the impact of lymph node density in favorable histology Wilms tumor: An analysis of the national cancer database.

INTRODUCTION: There is controversy about the role of lymph node (LN) sampling or dissection in the management of favorable histology (FH) Wilms tumor (WT), specifically how it performed and how it may impact survival. OBJECTIVE: The objective of this study was to analyze factors affecting LN sampling patterns and the impact of LN yield and density (number of positive LNs/LNs examined) on overall survival (OS) in patients with advanced-stage favorable histology Wilms tumor (FHWT). METHODS: The National Cancer Database (NCDB) was queried for patients with FHWT during 2004-2013. Demographic, clinical and OS data were abstracted for those who underwent surgical resection. Poisson regression was performed to analyze how factors influenced LN yield. Patients with positive LNs had LN density calculated and were further analyzed. RESULTS: A total of 2340 patients met criteria, with a median age at diagnosis of 3 years (range 0-78 years). The median number of LNs examined was three (range 0-87). Lymph node yield was affected by age, race, insurance, tumor size, laterality, advanced stage, LN positivity, and institutional volume. A total of 390 (16.6%) patients had LN-positive disease. Median LN density for these LN-positive patients was 0.38 (range 0.02-1) (Summary Figure). Estimated 5-year OS was significantly improved for those with LN density ≤0.38 vs. >0.38 (94% vs. 84.6%, P = 0.012). In this population, on multivariate analysis, age and LN density were significant predictors of OS. DISCUSSION: It is difficult to compile large numbers of cases in rare diseases like WT, and fortunately a large administrative database such as the NCDB can serve as a great resource. However, administrative data come with inherent limitations such as missing data and inability to account for a variety of factors that may influence LN yield and/or OS (specimen designation, pathologist experience, surgeon experience/volume, institutional Children's Oncology Group (COG) association, etc.). In this specific disease, the American Joint Committee on Cancer staging (captured by the NCDB) is different than the COG WT staging system that is used clinically, and the NCDB does not capture oncologic outcomes beyond OS. CONCLUSIONS: In a review of the NCDB, various factors associated with LN yield and observed LN density were identified to be significantly associated with OS in patients with LN-positive FHWT. This reinforces the need for adequate LN sampling at the time of WT surgery, to maximize surgical disease control. It was proposed that LN density as a metric may allow for improved risk-stratification, and possibly allow for therapeutic reduction in a sub-set of patients with low LN density.

Higgs physics at the CLIC electron-positron linear collider.

The Compact Linear Collider (CLIC) is an option for a future [Formula: see text] collider operating at centre-of-mass energies up to [Formula: see text], providing sensitivity to a wide range of new physics phenomena and precision physics measurements at the energy frontier. This paper is the first comprehensive presentation of the Higgs physics reach of CLIC operating at three energy stages: [Formula: see text], 1.4 and [Formula: see text]. The initial stage of operation allows the study of Higgs boson production in Higgsstrahlung ([Formula: see text]) and [Formula: see text]-fusion ([Formula: see text]), resulting in precise measurements of the production cross sections, the Higgs total decay width [Formula: see text], and model-independent determinations of the Higgs couplings. Operation at [Formula: see text] provides high-statistics samples of Higgs bosons produced through [Formula: see text]-fusion, enabling tight constraints on the Higgs boson couplings. Studies of the rarer processes [Formula: see text] and [Formula: see text] allow measurements of the top Yukawa coupling and the Higgs boson self-coupling. This paper presents detailed studies of the precision achievable with Higgs measurements at CLIC and describes the interpretation of these measurements in a global fit.

DUAL ACTION OF ARECOLINE ON ADRENAL FUNCTION AND GLUCOSE-GLYCOGEN HOMEOSTASIS IN METABOLIC STRESS IN MICE.

BACKGROUND: People chew betel nut (Areca catechu) for physical work and stress reduction, but it contains arecoline, which has both therapeutic value and untoward effects on endocrine and gonadal functions. OBJECTIVE: Aim of the present study is to investigate its role on adrenal with its target in metabolic stress in mice. MATERIALS AND METHODS: Mice were deprived of water / food, each for 5 days / treated with arecoline (10 mg / kg body wt daily for 5 days) / arecoline after water or food deprivation, for 5 days each. RESULTS: Water or food-deprivation caused adrenocortical hyperactivity, evident from abundance of enlarged mitochondria and smooth endoplasmic reticulum (SER) with elevation of corticosterone level (C: 68.31 ± 2.30, WD: 159.31 ± 4.10 / FD: 194.12 ± 3.40 µg/ mL). Arecoline treatment alone or in water deprivation (C: 68.31 ± 2.30, AR: 144.50 ± 4.33, AR+WD: 194.42 ± 3.35 µg/ mL) / food deprivation (AR + FD: 180.89 ± 4.51 µg/ mL) stress also stimulated adrenocortical activity as recorded in metabolic stress. In contrast, adrenomedullary activity was not altered following water/ food deprivation. Arecoline treatment alone or in metabolic stress suppressed adrenomedullary activity by showing depletion of chromaffin granules (E/NE?), epinephrine (E) and norepinephrine (NE) concentrations. Both the stress decreased blood glucose and liver glycogen levels. Arecoline treatment decreased blood glucose level, with a rise in liver glycogen level, but elevated blood glucose level in water deprivation unlike in starvation. CONCLUSION: Arecoline alone or in metabolic stress involves adrenal and probably other endocrine glands (pancreas, posterior pituitary and rennin-angiotensin system) to maintain homeostasis in metabolic stress in mice.

Time-constrained mother and expanding market: emerging model of under-nutrition in India.

BACKGROUND: Persistent high levels of under-nutrition in India despite economic growth continue to challenge political leadership and policy makers at the highest level. The present inductive enquiry was conducted to map the perceptions of mothers and other key stakeholders, to identify emerging drivers of childhood under-nutrition. METHODS: We conducted a multi-centric qualitative investigation in six empowered action group states of India. The study sample included 509 in-depth interviews with mothers of undernourished and normal nourished children, policy makers, district level managers, implementer and facilitators. Sixty six focus group discussions and 72 non-formal interactions were conducted in two rounds with primary caretakers of undernourished children, Anganwadi Workers and Auxiliary Nurse Midwives. RESULTS: Based on the perceptions of the mothers and other key stakeholders, a model evolved inductively showing core themes as drivers of under-nutrition. The most forceful emerging themes were: multitasking, time constrained mother with dwindling family support; fragile food security or seasonal food paucity; child targeted market with wide availability and consumption of ready-to-eat market food items; rising non-food expenditure, in the context of rising food prices; inadequate and inappropriate feeding; delayed recognition of under-nutrition and delayed care seeking; and inadequate responsiveness of health care system and Integrated Child Development Services (ICDS). The study emphasized that the persistence of child malnutrition in India is also tied closely to the high workload and consequent time constraint of mothers who are increasingly pursuing income generating activities and enrolled in paid labour force, without robust institutional support for childcare. CONCLUSION: The emerging framework needs to be further tested through mixed and multiple method research approaches to quantify the contribution of time limitation of the mother on the current burden of child under-nutrition.

Renal injury management in an urban trauma centre and implications for urological training.

INTRODUCTION: The aim of this study was to analyse the treatment and management of renal injury patients presenting to our major trauma unit to determine the likelihood of patients needing immediate nephrectomy. METHODS: The Trauma Audit and Research Network (TARN) database was used to review trauma cases presenting to our department between February 2009 and September 2013. Demographic data, mechanism and severity of injury, grade of renal trauma, management and 30-day outcome were determined from TARN data, electronic patient records and imaging. RESULTS: There were a total of 1,856 trauma cases, of which 36 patients (1.9%) had a renal injury. In this group, the median age was 28 years (range: 16-92 years), with 28 patients (78%) having blunt renal trauma and 8 (22%) penetrating renal trauma. The most common cause for blunt renal trauma was road traffic accidents. Renal trauma cases were stratified into American Association for the Surgery of Trauma (AAST) grades (grade I: 19%, grade II: 22%, grade III: 28%, grade IV: 28%, grade V: 0%). All patients with grade I and II injuries were treated conservatively. There were three patients (1 with grade III and 2 with grade IV renal injuries) who underwent radiological embolisation. One of these patients went on to have a delayed nephrectomy owing to unsuccessful embolisation. CONCLUSIONS: Trauma patients rarely require emergency nephrectomy. Radiological selective embolisation provides a good interventional option in cases of active bleeding from renal injury in haemodynamically stable patients. This has implications for trauma care and how surgical cover is provided for the rare event of nephrectomy.

Ovotesticular disorder of sexual development due to 47,XYY/46,XY/45,X mixed gonadal dysgenesis in a phenotypic male presenting as cyclical haematuria: clinical presentation and assessment of long-term outcomes.

Ovotesticular disorder of sexual differentiation (OTDSD) is a rare cause of disorder of sexual differentiation predominantly having 46,XX karyotype, female phenotype and ambiguous genitalia. We report a 15-year-old having male body habitus, axillary and pubic hair, well-developed penis and right-descended testis with history of penoscrotal hypospadias correction, presenting with three episodes of cyclical haematuria, who biochemically had normal serum testosterone (338 ng dl(-1) ) which increased following hCG stimulation (614 ng dl(-1) ), elevated estradiol (17.35 pg ml(-1) ) along with elevated luteinising hormone (11.3 mIU l(-1) ) and follicle-stimulating hormone (31 mIU l(-1) ). Ultrasonography followed by micturating cystourethrogram and cystoscopy confirmed the presence of prostate, uterus, cervix and vagina draining into the urogenital sinus continuing till the penile urethra and left intra-abdominal gonad. Patient underwent hysterectomy and left gonadectomy. Histopathologic study of resected gonad confirmed presence of ovotestis. Low estradiol (1.2 pg ml(-1) ) following gonadectomy confirmed the ovotestis origin of estradiol. Chromosomal analysis revealed complex karyotype predominant being 47,XYY (50%) followed by 46,XY (26%) and 45,X (24%). This is perhaps the first report of 47,XYY/46,XY/45,X causing OTDSD in a phenotypic male.

Periodic dynamics of fermionic superfluids in the BCS regime.

We study the zero temperature non-equilibrium dynamics of a fermionic superfluid in the BCS limit and in the presence of a drive leading to a time-dependent chemical potential µ(t). We choose a periodic driving protocol characterized by a frequency ω and compute the fermion density, the wavefunction overlap, and the residual energy of the system at the end of N periods of the drive. We demonstrate that the BCS self-consistency condition is crucial in shaping the long time behaviour of the fermions subjected to the drive and provide an analytical understanding of the behaviour of the fermion density nkF (where kF is the Fermi momentum vector) after a drive period and for large ω. We also show that the momentum distribution of the excitations generated due to such a drive bears the signature of the pairing symmetry and can be used, for example, to distinguish between s- and d-wave superfluids. We propose experiments to test our theory.

Interdistrict variations in child health status and health services utilization: lessons for health sector priority setting and planning from a cross-sectional survey in rural India.

BACKGROUND: There are limited data on interdistrict variations in child health status and health services utilization within the states of India. We conducted this study to identify and understand district-wise variations in child morbidity, mortality, healthcare seeking, and the status of health facilities in India. METHODS: A cross-sectional population-based cluster survey was conducted from April to July 2007 in 16 districts of eight states in India. Two districts with similar demographic profile and health criteria were selected from each study state. RESULTS: A total of 216 794 households and 24 812 under-5 children were surveyed. There were wide interdistrict variations in the health status of children within the same state and between different states across India. Interdistrict difference of >5 points/1000 live-births was found for infant mortality rate and under-5 mortality rate in all eight study states, while in six out of eight states this difference was >10 points/1000 live-births. Four states had a difference of >10 points/1000 live-births between respective districts for neonatal mortality rate. The interdistrict differences were also noted in childhood morbidity and health-seeking behaviour. Analysis of proportion of health facilities conforming to Indian public health standards revealed that the difference was m10% for availability of vaccines in five states, emergency services in three, laboratory services and logistics in four each, and referral facility in three of the eight study states. CONCLUSION: This study underscores an important information gap in the country where planners seem to rely heavily on a few selected national-level databases that may not be adequate at the micro level. The current process of sporadic health surveys also appears inadequate and inappropriate. There is a need for district-specific data for planning, improving quality of service and generating demand for health service utilization to improve child survival in India. The findings of this study may prove useful for child health programme planning in India.

Microfluidic sorting with blinking optical traps.

It is shown that by appropriately choosing the periodicity of a blinking optical trap only larger sized colloidal spheres can be selectively trapped out of a mixed population. This happens because smaller sized, more agile, spheres escape out of the trap volume during the off period of the trap beam. Therefore, by scanning an array of blinking traps over a mixed sample, bigger spheres can be forced to move with the traps and eventually could be taken to the output side. Experimental demonstration of sorting between 1 µm and 2 µm diameter silica spheres is presented.

Retrospective study of chikungunya outbreak in urban areas of India.

BACKGROUND & OBJECTIVES: A retrospective study on chikungunya outbreak in India in five States viz. Delhi, Madhya Pradesh, Orissa, Maharashtra and Kerala was conducted in 2007-2008 to know the distribution and determinants of chikungunya fever outbreak in India. METHODS: On the basis of high and low incidence of chikungunya fever, two districts from each State and two wards from the selected district were taken for random selection of 1000 households from 10 districts and 5 States. Semi-structured questionnaires were administered to individuals, patients, qualified health professionals and to stakeholders for collecting information. RESULTS: The educational background and occupation of the respondents showed variations across the study States. Only in high incidence ward of Maharashtra, water storage period for 3-6 days and emptying, drying of water containers on weekly basis was noted. The study through knowledge, attitude, belief, practice (KABP) obtained individual's perception of chikungunya fever, its prevention and control. Patients' expenditure on treatment was mainly recorded less than Rs 500 across study States. Health facility survey obtained an overview of the capacity of local health facilities. Stakeholders' perception regarding chikungunya fever was also noted. INTERPRETATION & CONCLUSIONS: The study revealed differences in awareness of chikungunya, cause of the disease, vector responsible, mode of transmission, biting time and elimination of breeding of mosquitoes statistically significant among high and low incidence wards of all the States. Expenditure on treatment was independent of economically active status and loss of man-days across all the States. Education and occupation did not have any relation with emptying/drying of water containers in high incidence wards. Strengthening of surveillance, information, education and communication (IEC) activities along with case management facilities may be provided by the State health department for prevention of chikungunya outbreaks in future. Stakeholders should be more involved in outbreak management and future planning.

Epidemiological analysis of hospitalized cases of dengue fever/dengue haemorrhagic fever and extent of breeding of Aedes aegypti in major hospitals in the National Capital Territory of Delhi (NCT Delhi), 2005–2009.

Dengue is a notifiable disease in the National Capital Territory of Delhi (NCT Delhi), India. All hospitals, both in the public and private sectors, are under obligation to report serologically confirmed cases of dengue to local health authorities. During the period 2005 to 2009, a total of 7402 serologically confirmed dengue cases were reported from the National Capital Territory of Delhi. Records of 5603 dengue cases (76%) admitted in hospitals were analysed for severity of disease. The trend of dengue has changed from cyclic to annual occurrence. DHF/DSS accounted for 518 (9.2%) of the admitted hospital cases in all age groups. The proportion of males found positive for dengue infection was 68% while females constituted 32%. The transmission season in NCT Delhi is the rainy season (July to October). Container indices monitored in six major hospitals remained persistently high in all the five years (range 1.5 to 23.9) and carried high potential for spatial spread of dengue infection to other parts of the NCT, Delhi region.

Cost-effectiveness of licensed treatment options for restless legs syndrome in the UK and Sweden.

OBJECTIVE: To estimate the cost-effectiveness of pramipexole versus no treatment and ropinirole in moderate to very severe idiopathic restless legs syndrome (RLS) in the UK and Sweden. METHODS: A Markov model was developed using clinical trial data for pramipexole and ropinirole. Model health states were based on the International RLS Study Group Rating Scale (IRLS) scores. Health states were: no (IRLS 0), mild (IRLS 1-14), moderate (IRLS 15-24), severe (IRLS 25-34), very severe RLS (IRLS 35-40) and death. Patients entered the model with an IRLS score > 15 matching the trial inclusion criteria of the pramipexole trials. Resource use and utilities were based on trial data, literature, a patient survey and a panel of physicians from the UK and Sweden in the absence of published information. A healthcare sector perspective was taken for the UK and a societal perspective for Sweden using 2004-2005 unit costs. The base case analysis took a 1-year timeframe. RESULTS: In the UK the incremental cost per quality-adjusted life year (QALY) for pramipexole was 3349 pounds sterling versus no treatment and a cost-saving of 92 pounds sterling against ropinirole. In Sweden, pramipexole produced cost-savings of Swedish Krona (SEK) 2381 (176 pounds sterling) versus no treatment and SEK 3564 (264 pounds sterling) against ropinirole. QALY gains in both countries were 0.095 versus no treatment and 0.007 versus ropinirole. Results compare well with UK cost-effectiveness thresholds of 20,000 pounds sterling/30,000 pounds sterling per QALY and are cost-saving for Sweden. One-way and probabilistic sensitivity analyses showed results to be robust. CONCLUSIONS: Pramipexole is cost-effective compared to no treatment and ropinirole for patients with moderate to very severe RLS.

Use of an optical surface scanner in assessment of outcome following rhinoplasty surgery.

OBJECTIVE: To demonstrate the use of an optical surface scanner, with associated software, in the assessment of rhinoplasty patients, and to discuss the possible clinical applications of this technology in the future. DESIGN: Case study analysis of pre- and post-operative scans of a patient undergoing septorhinoplasty at Whipps Cross University Hospital, London, UK. SUBJECT: A 21-year-old man undergoing septorhinoplasty underwent pre-operative optical surface scanning of his face. The scans were repeated at one week and one year post-operatively. Software developed at University College London was then used to analyse the scans. RESULTS: The scans clearly showed that the man's dorsal hump had been well reduced and the nose straightened, with a resulting 1600 mm3 gain on the right side and a 1000 mm3 loss on the left side of the nose. Tip projection had also been achieved. CONCLUSION: This technique allowed objective quantification of facial features and analysis of change. It may well prove useful in the future in predicting change following surgical intervention.

Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen suitable for allogeneic transplantation that maintains the graft versus malignancy effect.

Reduced intensity conditioning (RIC) for allogeneic stem cell transplantation allows stable donor cell engraftment with the maintenance of a graft versus malignancy effect. Many different regimens exist employing various combinations of chemotherapy, radiotherapy and T-cell depletion. We examined the role of non-T-cell depleted RIC regimens in 56 patients with haematological malignancies. Patients received fludarabine phosphate for 5 days (30 mg/m2 in 35 patients, 25 mg/m2 in 21 patients) and melphalan for 1 day (140 mg/m2 in 36 patients, 100 mg/m2 in 20 patients). Immunosuppression was with CyA alone in 33 patients and CyA/MTX in 23 patients. Twenty-four of the 26 patients with chimerism data showed >95% donor chimerism at 3 months post transplant. aGVHD occurred in 18% of patients receiving CyA/MTX compared to 53% of patients receiving CyA. The 100-day mortality rate was 0.16 (95%CI 0.08-0.28) and 1-year nonrelapse mortality was 0.24 (95%CI 0.13-0.38). Thirty-three patients remained alive and in CR at a median of 19 months post transplant (range 3-38 months). We have shown that patients transplanted with fludarabine phosphate, melphalan 100 mg/m2 and with CyA/MTX as post transplant immunosuppression can achieve good disease control with an acceptable level of toxicity. Further studies are required to confirm these findings.

An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis.

The majority of patients with multiple sclerosis (MS) develop troublesome lower urinary tract symptoms (LUTS). Anecdotal reports suggest that cannabis may alleviate LUTS, and cannabinoid receptors in the bladder and nervous system are potential pharmacological targets. In an open trial we evaluated the safety, tolerability, dose range, and efficacy of two whole-plant extracts of Cannabis sativa in patients with advanced MS and refractory LUTS. Patients took extracts containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD; 2.5 mg of each per spray) for eight weeks followed by THC-only (2.5 mg THC per spray) for a further eight weeks, and then into a long-term extension. Assessments included urinary frequency and volume charts, incontinence pad weights, cystometry and visual analogue scales for secondary troublesome symptoms. Twenty-one patients were recruited and data from 15 were evaluated. Urinary urgency, the number and volume of incontinence episodes, frequency and nocturia all decreased significantly following treatment (P <0.05, Wilcoxon's signed rank test). However, daily total voided, catheterized and urinary incontinence pad weights also decreased significantly on both extracts. Patient self-assessment of pain, spasticity and quality of sleep improved significantly (P <0.05, Wilcoxon's signed rank test) with pain improvement continuing up to median of 35 weeks. There were few troublesome side effects, suggesting that cannabis-based medicinal extracts are a safe and effective treatment for urinary and other problems in patients with advanced MS.