A Case for Data Commons: Toward Data Science as a Service.

Data commons collocate data, storage, and computing infrastructure with core services and commonly used tools and applications for managing, analyzing, and sharing data to create an interoperable resource for the research community. An architecture for data commons is described, as well as some lessons learned from operating several large-scale data commons.

Phase Ib study of HSP90 inhibitor, onalespib (AT13387), in combination with paclitaxel in patients with advanced triple-negative breast cancer.

Background: Heat shock protein 90 (HSP90) is a molecular chaperone required for stabilization of client proteins over-activated in triple-negative breast cancer (TNBC). Over-expression of HSP90 client proteins has been implicated in paclitaxel resistance. Onalespib (AT13387) is a potent inhibitor of HSP90 that could improve paclitaxel efficacy when administered in combination. Design: This phase Ib trial administered onalespib with paclitaxel in patients with advanced TNBC to assess safety and establish a recommended phase II dose (RP2D). Objectives: The primary objectives were determining the dose-limiting toxicities and maximum tolerated dose of combination therapy. Secondary objectives included pharmacokinetic (PK) analysis and determination of overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Methods: Patients with advanced TNBC were treated with standard dose intravenous paclitaxel in combination with intravenous onalespib at doses ranging from 120 to 260 mg/m2 administered on days 1, 8, and 15 of a 28-day cycle using a standard 3 + 3 design. A total of 15 patients were enrolled to dose expansion cohort at RP2D to confirm safety profile. Results: Thirty-one patients were enrolled in the study, of which over 90% had received prior taxane therapy. Paclitaxel was given for metastatic disease in 23% of patients. Adverse events (AEs) included anemia (grade 3: 20%), lymphopenia (grade 3: 17%), and neutropenia (grade 3: 33%, grade 4: 4%). The most frequent grade ⩾3 non-hematologic AE was diarrhea (7%). The established RP2D was 260 mg/m2 onalespib when given with paclitaxel at 80 mg/m2. PK analysis revealed a modest drug interaction profile for onalespib in the combination regimen. ORR was 20%. Three patients achieved complete responses, all of whom had received prior taxane therapy. Median DOR was 5.6 months; median PFS was 2.9 months. Conclusion: Combination treatment with onalespib and paclitaxel had an acceptable toxicity profile and RP2D was determined to be 260 mg/m2 of onalespib. Combination therapy showed antitumor activity in patients with advanced TNBC. Trial registration: Onalespib and paclitaxel in treating patients with advanced TNBC https://clinicaltrials.gov/ct2/show/NCT02474173.

Phase 1b study of HSP90 inhibitor called onalespib in combination with paclitaxel in patients with advanced triple-negative breast cancer This Phase 1b study demonstrated that treatment with a combination of onalespib and paclitaxel was reasonably well tolerated by most patients. Onalespib at 260 mg/m² given intravenously on days 1, 8 and 15 on 28-day cycles in combination with standard dose and schedule of paclitaxel was established as the recommended phase 2 dose for further clinical development. Despite minor drug-drug interactions between these 2 agents, onalespib did not alter paclitaxel exposure and paclitaxel did not affect exposure to onalespib. While onalespib with paclitaxel combination therapy did not yield durable objective responses or prolonged progression-free survival, there were several patients with long-lasting benefit from this combination including patients who previously experienced progression on taxane therapy.

Combat urologic trauma in US military overseas contingency operations.

BACKGROUND: This article reports on the occurrences and patterns of genitourinary (GU) trauma in the contemporary high-intensity conflict of the overseas contingency operations (OCOs). METHODS: The Joint Theater Trauma Registry was queried for all US military members who received treatment for GU wounds and concomitant injuries sustained in OCOs for >75 months between October 2001 and January 2008. RESULTS: Of the 16,323 trauma admissions annotated in the Joint Theater Trauma Registry, 819 (5%) had one or more GU injuries. Of the GU casualties, 90% were sustained in Iraq and 65% were because of explosions. The average casualty age was 26 years (range, 18-58 years) and 98.5% were men. There were 887 unique GU injuries distributed as follows: scrotum, 257 (29.0%); kidney, 203 (22.9%); bladder, 189 (21.3%); penis, 126 (14.2%); testicle, 81 (9.1%); ureter, 24 (2.7%); and urethra, 7 (0.8%). Of the 203 patients with kidney injuries, 22% went to the operating room with 31 patients having nephrectomies. There were 189 bladder injuries with 26 patients (14%) having concomitant pelvic fractures. CONCLUSIONS: This is the largest report of GU injuries during any military conflict. The distribution and percentage of casualties with GU injuries in the OCO are similar to those of previous conflicts. Consideration should be given to personnel protective equipment for the areas associated with GU injuries and predeployment training directed at the care of these injuries.

Respiratory syncytial virus infections in children with acute myeloid leukemia: a report from the Children's Oncology Group.

BACKGROUND: Morbidity and mortality related to respiratory syncytial virus (RSV) in pediatric acute myeloid leukemia (AML) is not known. PROCEDURE: We combined data from three Children's Oncology Group AML studies and determined the prevalence of RSV infection and RSV-related mortality in children treated for de novo AML. RESULTS: We found that the prevalence of RSV infection ranged from 0% to 1% in induction and between 0.3 and 2.2% in consolidation. Four children died from RSV resulting in RSV-specific mortality of 0.2% among all children. However, the risk of RSV-related mortality among RSV infection episodes was high (4/40, 10%). CONCLUSIONS: RSV infections and deaths are rare in pediatric AML.

Detecting Spatial Patterns of Disease in Large Collections of Electronic Medical Records Using Neighbor-Based Bootstrapping.

We introduce a method called neighbor-based bootstrapping (NB2) that can be used to quantify the geospatial variation of a variable. We applied this method to an analysis of the incidence rates of disease from electronic medical record data (International Classification of Diseases, Ninth Revision codes) for ∼100 million individuals in the United States over a period of 8 years. We considered the incidence rate of disease in each county and its geospatially contiguous neighbors and rank ordered diseases in terms of their degree of geospatial variation as quantified by the NB2 method. We show that this method yields results in good agreement with established methods for detecting spatial autocorrelation (Moran's I method and kriging). Moreover, the NB2 method can be tuned to identify both large area and small area geospatial variations. This method also applies more generally in any parameter space that can be partitioned to consist of regions and their neighbors.

Influence of sodium intake on Amphotericin B-induced nephrotoxicity among extremely premature infants.

UNLABELLED: Amphotericin B (AmphoB) remains the preferred therapy for invasive fungal infections despite many side effects, such as nephrotoxicity and electrolyte imbalance. Our previous study suggested that high sodium (Na) intake >4 mEq/kg per day may be associated with lower nephrotoxicity in extremely premature infants treated with AmphoB. Subsequently, it became a standard of care in our unit to administer Na >4 mEq/kg per day to extremely premature infants treated with AmphoB. The purpose of this study was to evaluate the effect of high Na intake > 4 mEq/kg per day on the incidence of AmphoB-induced nephrotoxicity among extremely premature infants with birth weight <1250 gm. All extremely premature infants with birth weight <1250 gm born between 1992 and 2004 and treated with AmphoB for systemic fungal infections were included in the study. The study infants were divided into two groups: a control (CL) group (1/1992-12/1999, n = 21) consisting of extremely premature infants given a maintenance Na intake during AmphoB therapy, and a high sodium intake (High Na) group (1/2000-12/2004, n = 16) consisting of extremely premature infants given a high Na intake >4 mEq/kg per day during AmphoB therapy. Nephrotoxicity was defined as serum creatinine levels >1 mg/dl, urinary output (UOP) < 1 ml/kg per hour or a decrease in UOP of 50%, compared with the previous 2 days, and persisting for at least 2 days. Invasive fungal infection was diagnosed in 5.7% of the infants (44/763 infants). Thirty-seven infants were eligible for the study and seven were excluded. There were no differences between the two groups in gestational age, birth weight, age at fungal infection diagnosis, length of AmphoB therapy, daily fluid intake or hyponatremia. Nephrotoxicity was significantly higher in the CL group than in the High Na group (13/21 vs. 3/16; P = 0.02). In the CL group, nephrotoxicity occurred at (mean +/- SD) 1.9 +/- 3.2 days after the initiation of AmphoB treatment and lasted for 5.5 +/- 4.7 days. In this group, nephrotoxicity occurred in two of the 13 infants before the initiation of AmphoB therapy. In the High Na group, nephrotoxicity occurred before the start of AmphoB therapy in two of the three infants. In the third infant, nephrotoxicity lasted for 1 day. Mean Na intake was not different between the two groups during the 4-day period prior to AmphoB therapy. Mean Na intake during the first 10-day period of AmphoB therapy was significantly lower in the CL group (3.7 vs 6.2; P < 0.001). CONCLUSION: High Na intake was associated with a reduction in the incidence of AmphoB-induced nephrotoxicity in extremely premature infants with birth weight <1250 gm. We recommend the use of a high Na intake of >4 mEq/kg per day for extremely premature infants during Amphotericin B therapy.

Effects of fluid and electrolyte management on amphotericin B-induced nephrotoxicity among extremely low birth weight infants.

OBJECTIVE: Greater use of invasive procedures and aggressive antimicrobial therapy predispose extremely low birth weight (ELBW) infants to systemic fungal sepsis. Despite its adverse effects (including renal and electrolyte disturbances), amphotericin B (amphoB) remains the preferred drug for fungal therapy. Multiple studies have indicated that sodium loading may prevent renal toxicity among animals and human adults. The effects of fluid and electrolyte management on amphoB-induced nephrotoxicity among ELBW infants have not been evaluated extensively. The purpose of this study was to examine the effects of fluid and electrolyte management on amphoB-induced nephrotoxicity among ELBW infants. DESIGN/METHODS: The medical records were reviewed for all ELBW infants (birth weights of < or =1250 g) who developed systemic fungal sepsis, requiring amphoB therapy, between January 1992 and December 2000. Demographic, clinical, and laboratory data were collected from the medical records for each patient. RESULTS: Fungal sepsis requiring amphoB treatment developed for 4.4% of ELBW infants (25 of 573 infants), with a gestational age of 25 +/- 1 weeks and a birth weight of 738 +/- 37 g, at a postnatal age of 16 +/- 2 days. Renal compromise, as manifested by low urine output and high creatinine levels, occurred for 44% of those infants (11 of 25 infants). There was no difference between the infants who developed renal compromise (renal compromise group [RCG], n = 11) and those who did not (no-renal-compromise group [NCG], n = 14) with respect to birth weight, gestational age, and risk factors predisposing the infants to fungal sepsis. The RCG demonstrated a decrease in urine output by 3.4 +/- 2 days and an increase in serum creatinine levels by 3.9 +/- 2 days after the initiation of amphoB therapy. Infants in the RCG had a significantly higher incidence of hyponatremia, compared with infants in the NCG (7 of 11 infants vs 0 of 14 infants), with no significant difference in the incidences of hypokalemia (2 of 11 infants vs 0 of 14 infants). Infants in the RCG, compared with infants in the NCG, had significantly lower mean daily sodium intakes in the 4 days before the initiation of amphoB therapy (2.6-2.9 mEq/kg per day vs 4.2-4.7 mEq/kg per day) and in the first 4 days of amphoB treatment (2.7-3.1 mEq/kg per day vs 4.5-5.6 mEq/kg per day). Mean daily sodium intakes were not statistically significantly different between the 2 groups between day 5 and day 10 of amphoB therapy. Infants in the RCG tended to have lower mean daily potassium intakes in the 4 days before the initiation of amphoB therapy and during the first 4 days of amphoB therapy. Subsequently, the mean daily potassium intakes remained not statistically significantly different between the groups. Mean daily fluid intakes were not different between the groups. CONCLUSIONS: Conventional amphoB combined with adequate hydration and higher sodium intakes of >4 mEq/kg per day may provide effective protection against amphoB-induced nephrotoxicity among ELBW infants. Our data confirm the published results of animal and human adult studies and suggest that higher sodium intakes may prevent renal compromise during amphoB therapy among ELBW infants.

Higiene bucal: su repercusión en pacientes con tratamientos ortodóncicos / Oral higiene: its impacto on patients with orthodontic treatment

El éxito de los tratamientos ortodóncicos aplicados en la adolescencia radica en mantener una higiene bucal buena, la cual favorece un buen funcionamiento y evita la aparición de complicaciones en los pacientes, asociado con un correcto cepillado de los dientes y de los aparatos ortodóncicos, lo que es un elemento esencial e importante para un tratamiento exitoso, unido al mantenimiento saludable de las encías, prevención de las caries y peridontitis. Se realizó un estudio descriptivo en 50 pacientes de uno u otro sexo y raza, con edades comprendidas entre 12-16 años, procedentes de la Consulta de Ortodoncia de la Clínica Estomatológica H y 21, en el período de marzo-agosto del 2006, los cuales reciben tratamiento ortodóncico, con el objetivo de determinar la higiene bucal durante el tratamiento. Predominó el sexo masculino y el grupo de 12-14 años. Se observó que el 92 por ciento de los pacientes estudiados se categorizó con índice de higiene bucal simplificado bueno y solo el 8 por ciento con un índice de higiene bucal simplificado regular. Finalmente el índice de higiene bucal simplificado del colectivo fue bueno. Se recomienda incrementar y fomentar aún más el mantenimiento de la higiene bucal, para obtener un buen éxito durante el tratamiento ortodóncico y por lo tanto, que el paciente pueda disfrutar de una bonita sonrisa sin afectaciones psicológica(AU)

The success of orthodontic treatment applied in adolescence lies in keeping a good oral hygiene, which favors good functioning of teeth and avoids the occurence of complications, associated to good brushing of teeth and of orthodontic appliances that is an eseential and important element for healthy conditon of gingivae, prevention of dental caries and peridontitis. A descriptive study of 50 patients of either sex and any race aged 12-16 years from Orthodontic Service of Dental Clinc H y 21 was conducted from March to August, 2006. They received orthodontic treatment to determine their oral hygiene in the course of treatment. It was observed that males and 12-14 y age group prevailed; 92 per cent and 8 per cent of patients were classified as having good and regular simplified oral hygiene index respectively. Finally, the index of the group was regarded as good. The study recommended to increase and foster oral hygiene to succeed in orthodontic treatment and thus the patient can enjoy a beatiful smile without psychological disorders(AU)