Early weight gain in infants with Robin sequence after mandibular distraction.

This retrospective cohort study was performed to assess weight gain in infants with Robin sequence (RS) treated by mandibular distraction osteogenesis (MDO). The primary outcome variable was average daily weight gain for the following time periods: (1) birth to MDO (T1), (2) MDO to distractor removal (T2), (3) distractor removal to 6 months later (T3), and (4) 6 months to 12 months following distractor removal (T4). Published growth curves were used for comparison. Differences were assessed using the Wilcoxon matched-pairs signed rank test. Twenty-two infants were included in the study. During T1, the infants had 9.47 ± 12.61 g/day less weight gain than expected (P = 0.001). However, for T2, T3, and T4, the infants demonstrated 3.48 ± 6.17 g/day (P = 0.028), 2.19 ± 4.47 g/day (P = 0.030), and 1.83 ± 3.25 g/day (P = 0.028) more weight gain than expected. Feeding tube use resulted in improved weight gain during T1 (P < 0.001), but was associated with poorer weight gain in T3 (P = 0.003) and T4 (P = 0.001). In conclusion, infants with RS treated by MDO demonstrated poorer weight gain relative to their peers between birth and the MDO operation. However, from the MDO procedure to 12 months post-distractor removal, infants who had MDO showed faster weight gain than their age-matched peers.

Soil Carbon Pools in Dryland Agroecosystems as Affected by Several Years of Drought.

No-till and increased cropping intensity (CI) can increase yield and soil organic C (SOC) in the US Great Plains compared with traditional wheat ( L.)-fallow management. However, gains in SOC and other C pools may not be permanent. Increasing frequency of drought may reduce C inputs and potentially reverse gains accrued during wetter periods. This study examined the effect of drought on the persistence of SOC with two objectives: (i) to determine soil C pools (0-20 cm) after 24 yr in no-till as influenced by potential evapotranspiration (PET), landscape position (slope), and CI; and (ii) to compare the size of the C pools after the first 12 yr (wet) versus the subsequent 12 yr, notable for frequent droughts. Rotations were wheat-corn ( L.)-fallow (WCF), continuous cropping (CC), and a grass Conservation Reserve Program mixture planted across slopes at three sites in Colorado with similar precipitation but increasing PET. After 24 yr, water-soluble organic C increased with CI from WCF to CC to grass with 250, 340, and 440 kg C ha, respectively. Soil microbial biomass C also increased with CI-1500, 1660, and 2135 kg C ha for WCF, CC, and grass, respectively. The particulate organic matter C pool had a three-way interaction with PET, slope, and CI. Overall, between Years 12 and 24, SOC increased in grass by 16.9%, with a rate of 425 kg C ha yr sequestration compared with 10.5 and 1.4% for the WCF and CC systems, respectively.

Time to treatment and survival in triple negative breast cancer patients receiving trimodality treatment in the United States.

BACKGROUND: Time from diagnosis to treatment for breast cancer patients has been linked to outcomes. Our goal was to assess the relationship between survival, time to first treatment (TFT), and time to treatment completion (TTC) in Stage I-III triple negative breast cancer (TNBC) receiving trimodality therapy (surgery, chemotherapy, and radiation). METHODS: National Cancer Database (NCDB) was queried for TNBC patients diagnosed with Stage I-III disease from 2010 to 2011 who received all treatments (surgery, chemotherapy, radiation) within 18 months of diagnosis. Multivariate analysis controlled for age, stage, operation, neoadjuvant chemotherapy (NAC), and comorbidities. RESULTS: 17,717 women were included. Most had early stage disease (34.1% Stage 1; 48.2% Stage 2) treated with lumpectomy (69.2%) and adjuvant chemotherapy (63.3%). During follow-up (2.8 ±â€¯1.1 years), mortality was 11.4%. TFT was 34.8 days for NAC and 35.6 days for surgery. Multivariate analysis demonstrated no mortality difference when considering TFT in 30 day (p = 0.43) or 6 week (p = 0.91) intervals. When separating into NAC or surgery first, there remained no mortality difference when considering TFT in 30 day (NAC p = 0.96, surgery p = 0.26) or 6 week (NAC p = 0.91, surgery p = 0.91) intervals. Overall, TTC was 9.0 ±â€¯1.8 months. When dividing patients into tertiles by TTC, multivariate analysis demonstrated no survival difference between groups (p = 0.9). There was also no mortality difference for each 30 day increased TTC (p = 0.40). CONCLUSIONS: In Stage I-III TNBC patients receiving trimodality therapy, TFT (NAC or surgery) and TTC do not impact short-term survival if TTC is <18 months.

Surotomycin versus vancomycin in adults with Clostridium difficile infection: primary clinical outcomes from the second pivotal, randomized, double-blind, Phase 3 trial.

BACKGROUND: The available treatment options for Clostridium difficile infection (CDI) are limited by high recurrence rates. Surotomycin was a novel bactericidal cyclic lipopeptide in development to treat CDI that demonstrated non-inferiority to vancomycin in a Phase 2 trial. OBJECTIVES: To assess surotomycin safety and clinical response (non-inferiority versus vancomycin) at the end of treatment (EOT) of CDI. Additionally, to assess surotomycin response over time and sustained response at 30-40 days post-EOT (superiority versus vancomycin). PATIENTS AND METHODS: Patients with CDI were randomized (1:1) to receive twice-daily oral surotomycin 250 mg alternating with twice-daily placebo or four-times-daily oral vancomycin 125 mg for 10 days in this Phase 3, double-blind, multicentre, international trial. Clinical response over time and sustained clinical response were monitored until the end of the trial, through a follow-up period of 30-40 days. Clinical Trial Registration: NCT01598311. RESULTS: A total of 285 and 292 patients with confirmed CDI were randomized to receive surotomycin and vancomycin, respectively. Surotomycin-associated clinical response at EOT was non-inferior to vancomycin (surotomycin/vancomycin: 83.4%/82.1%; difference 1.4%, 95% CI - 4.9, 7.6). Following treatment with surotomycin, both clinical response over time (stratified log-rank test, P = 0.277) and sustained clinical response (63.3%/59.0%; difference 4.3%, 95% CI - 3.6, 12.2) did not demonstrate superiority versus vancomycin at end of trial. Both treatments were generally well tolerated. CONCLUSIONS: Surotomycin demonstrated non-inferiority to vancomycin for CDI clinical response at EOT. Surotomycin did not demonstrate superiority to vancomycin for clinical response over time or sustained clinical response rate.

Early genetic restoration of lubricin expression in transgenic mice mitigates chondrocyte peroxynitrite release and caspase-3 activation.

OBJECTIVE: This study investigated the ability of endogenous lubricin secretion to restore joint health following a brief <21 day, postnatal lubricin-null state, in a C57BL/6J Prg4 gene trap (GT) mouse under the control of cre-recombinase. Previously we showed that re-expression of lubricin at 21 days was partly restorative of joint lubrication. DESIGN: The tibio-femoral joints of adult C57BL/6J mice containing lubricin, lacking lubricin, and postnatally lacking lubricin until restoration of lubricin expression at 7 days or 14 days of age were evaluated ex vivo. At 8-weeks of age, whole joint coefficient of friction (COF), and caspase-3 activation were measured and the tibial-femoral joints histologically analyzed for degenerative changes, following progressive cyclic loading. The peroxynitrite content of femoral head cartilage from these mice prior to cyclic loading was measured. RESULTS: Mice that underwent gene recombination at 7 and 14 days of age did not reestablish low COF as joint cycling time increased and were histopathologically indistinguishable from the joints of lubricin-null littermates. However, cartilage from tibio-femoral joints that underwent recombination at 7 and 14 days of age had significantly fewer caspase-3 positive cells and significantly reduced peroxynitrite content compared to lubricin-null littermates. CONCLUSIONS: The biological effects of lubricin, which include limiting inflammation via peroxynitrite production and caspase-3 activation, may be achieved without completely restituting low COF. However, fully recapitulating low COF may require undamaged cartilage surfaces or absence of biofouling, which may interfere with the activity of lubricin.

Local adaptation along an environmental cline in a species with an inversion polymorphism.

Polymorphic inversions are ubiquitous across the animal kingdom and are frequently associated with clines in inversion frequencies across environmental gradients. Such clines are thought to result from selection favouring local adaptation; however, empirical tests are scarce. The seaweed fly Coelopa frigida has an α/ß inversion polymorphism, and previous work demonstrated that the α inversion frequency declines from the North Sea to the Baltic Sea and is correlated with changes in tidal range, salinity, algal composition and wrackbed stability. Here, we explicitly test the hypothesis that populations of C. frigida along this cline are locally adapted by conducting a reciprocal transplant experiment of four populations along this cline to quantify survival. We found that survival varied significantly across treatments and detected a significant Location x Substrate interaction, indicating local adaptation. Survival models showed that flies from locations at both extremes had highest survival on their native substrates, demonstrating that local adaptation is present at the extremes of the cline. Survival at the two intermediate locations was, however, not elevated at the native substrates, suggesting that gene flow in intermediate habitats may override selection. Together, our results support the notion that population extremes of species with polymorphic inversions are often locally adapted, even when spatially close, consistent with the growing view that inversions can have direct and strong effects on the fitness of species.

Variability of upper firn processes in West Antarctica observed with GPS reflectometry, 2007-2017.

Land ice loss from Antarctica is a significant and accelerating contribution to global sea-level rise; however, Antarctic mass-balance estimates are complicated by insufficient knowledge of surface mass-balance processes such as snow accumulation. These variables are challenging to observe on a continental scale and in situ data are sparse, so we largely rely on estimates from atmospheric models. Here, we employ a novel method, GPS interferometric reflectometry (GPS-IR), to measure upper (<2 m) firn-column thickness changes across a 23-station GPS array in West Antarctica. We compare the results with antenna heights measured in situ to establish the method's daily uncertainty (0.06 m) and with output from two atmospheric reanalysis products to categorize spatial and temporal variability of near-surface processes. GPS-IR is an effective method for monitoring surface mass-balance processes that can be applied to both historic GPS datasets and future experiments to provide critical in situ observations of processes driving surface-height evolution.

Helicase-primase as a target of new therapies for herpes simplex virus infections.

The seminal discovery of acyclovir 40 years ago heralded the modern era of truly selective antiviral therapies and this drug remains the therapy of choice for herpes simplex virus infections. Yet by modern standards, its antiviral activity is modest and new drugs against novel molecular targets such as the helicase-primase have the potential to improve clinical outcome, particularly in high-risk patients. A brief synopsis of current therapies for these infections and clinical need is provided to help provide an initial perspective. The function of the helicase-primase complex is then summarized and the development of new inhibitors of the helicase-primase complex, such as pritelivir and amenamevir, is discussed. We review their mechanism of action, propensity for drug resistance, and pharmacokinetic characteristics and discuss their potential to advance current therapeutic options. Strategies that include combinations of these inhibitors with acyclovir are also considered, as they will likely maximize clinical efficacy.

Effect of development system on growth and reproductive performance of beef heifers.

Reproductive performance was evaluated in beef heifers born over a 2-yr period to determine the effects of target breeding weight (TBW) and development system (SYS) on growth and subsequent reproductive efficiency. Spring-born Angus heifers (253 ± 0.7 kg) were randomly allocated over 2 consecutive yr (yr 1, n = 80; yr 2, n = 96) to be developed to either 55% (350 kg) of mature BW (moderate gain, MG) or 62% (395 kg) of mature BW (high gain, HG). Each MG and HG group was further assigned to 1 of 2 replicated systems: (1) bale graze bromegrass-alfalfa round bales in field paddocks (BG) or (2) fed bromegrass-alfalfa round bales in drylot pens (DL). Heifers were fed a diet of bromegrass-alfalfa hay (56.9% TDN; 9.8% CP) and barley grain supplement (85.1% TDN; 12.3% CP). After the 202-d development period, heifers were exposed to bulls for a 63-d breeding season. Target BW × SYS interactions were not detected for any measured parameters. During the winter development period, MG heifers had lower (P = 0.01) ADG than HG heifers and MG heifers had lighter (P = 0.01) BW at breeding. The proportion of heifers attaining puberty by 14.5 mo of age was less (P = 0.05) in MG (20 ± 4%) than HG heifers (52 ± 3%). From the end of the 202-d development period to pregnancy diagnosis, ADG was greater (P = 0.04) in MG heifers than HG heifers (0.83 vs. 0.71 kg/d). First-calf pregnancy rates were 86 and 88% for MG and HG heifers, respectively (P = 0.41). Second- and third-calf pregnancy rates of cows, developed in either a MG or HG system as heifers, were not different (P = 0.74; 94.7 vs. 95.9% and 93.8 vs. 93.9%, respectively). Economic analysis revealed a $58 reduced development cost for heifers developed to 55% compared with 62% of mature BW without a loss in reproductive performance.

Pharmacological comparison of peristaltic effects in rats and mice.

INTRODUCTION: Conscious rodent models are commonly used to assess the effects of new chemical entities on propulsion (transit) time in the gastrointestinal system. This study was designed to compare three compounds clinically known to cause constipative (morphine sulfate and propantheline bromide) and laxative (metoclopramide hydrochloride) effects on transit time in rats and mice and to note if there are differences between the species. METHODS: Compounds were dosed in conscious rats and mice. At 0.5-2.0h post dosing (estimated time to maximal plasma concentration of each compound) animals were gavaged with an appropriate volume (based on weight) of 10% activated powdered carbon suspended in 5% gum arabic. Forty-five minutes following dosing the animals were sacrificed by CO2 asphyxiation and the small intestine was removed. The position of the leading edge of the charcoal was measured relative to the total length of the intestinal segment. RESULTS: The compounds tested produced variable statistical differences in transit time between species. Morphine and propantheline produced dose-dependent increases in transit time, and metoclopramide decreased transit time, statistically significant in both rodent models. DISCUSSION: The present data demonstrate that at similar doses rats and mice can be used interchangeably for transit studies. Mice were more sensitive to transit changes at higher doses of the compounds tested.

MRSA in pork production shower facilities: an intervention to reduce occupational exposure.

Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization has been documented in swine and swine workers. MRSA has also been found in the shower facilities of conventional swine farms. We previously conducted a review of the literature to identify measures used to reduce MRSA prevalence in athletic facilities. In this study, we evaluated those measures for adaptability to the pork production environment. A best practices protocol was developed to reduce MRSA levels in pork production shower facilities and implemented in two conventional swine production systems.

A Case of Agonadism, Skeletal Malformations, Bicuspid Aortic Valve, and Delayed Development with a 16p13.3 Duplication Including GNG13 and SOX8 Upstream Enhancers: Are Either, Both or Neither Involved in the Phenotype?

We report a female patient with delayed growth and development, skeletal and cardiac defects, and a male XY sex chromosome complement with early failure of gonad development. SRY sequencing was normal. Array comparative genome hybridization (CGH) analysis revealed a gain in copy number in the subtelomeric region of the short arm of chromosome 16, encompassing a region of approximately 560 kb in size including GNG13 which may be involved in ovarian development. The proximal breakpoint of the duplication maps about 18 kb upstream of SOX8 and involves evolutionary conserved regulatory elements. SOX8, like SOX9, is a transcription factor expressed in many tissues, including neural crest, nervous system, muscle, cartilage, adrenal gland, kidney, and testis. There was no increase in GNG13 or SOX8 expression in the patient's lymphoblastoid line. It is possible that an alteration of SOX8 or/and GNG13 expression is responsible for the multiple congenital anomalies and sex reversal in our patient.

Retrofitting tractors with rollover protective structures: perspective of equipment dealers.

This study was one of a cluster of studies that originated via requests for proposals from the NIOSH National Agricultural Tractor Safety Initiative. The present study design consisted of several steps: (1) formation of an advisory group, (2) development and testing of a standard paper self-responding survey instrument, (3) sample selection of farm equipment dealers, (4) administration of the survey, (5) assessment and analysis of the survey, and (6) in-person response panel of dealers (n = 80) to review results of the questionnaire for further definition and sharpening of the recommendations from the survey. A key finding is that most dealers do not currently sell or install ROPS retrofit kits. Barriers cited by dealers included (1) actual or perceived lack of farmer demand, (2) injury liability, (3) expensive freight for ordering ROPS, (4) lack of dealer awareness of the magnitude of deaths from tractor overturns and the high life-protective factor of ROPS, and (5) difficulty and incursion of non-recoverable expenses in locating and obtaining specific ROPS. Despite not currently selling or installing ROPS, dealers responded favorably about their future potential role in ROPS promotion and sales. Dealers were willing to further promote, sell, and install ROPS if there was demand from farmers. Recommendations include establishing a ROPS "clearing house" that dealers could contact to facilitate locating and obtaining ROPS orders from customers. Additional recommendations include education and social marketing targeting farm machinery dealers as well farmers, manufacturers, and policy makers.

User-adaptive reminders for home-based medical tasks. A case study.

OBJECTIVES: We present a prototype adaptive reminder system for home-based medical tasks. The system consists of a mobile device for reminder presentation and ambient sensors to determine opportune moments for reminder delivery. Our objective was to study interaction with the prototype under naturalistic living conditions and gain insight into factors affecting the long-term acceptability of context-sensitive reminder systems for the home setting. METHODS: A volunteer participant used the prototype in a residential research facility while adhering to a regimen of simulated medical tasks for ten days. Some reminders were scheduled at fixed times during the day and some were automatically time-shifted based on sensor data. We made a complete video and sensor record of the stay. Finally, the participant commented about his experiences with the system in a debriefing interview. RESULTS: Based on this case study, including direct observation of individual alert-action sequences, we make four recommendations for designers of context-sensitive adaptive reminder systems. Captured metrics suggest that adaptive reminders led to faster reaction times and were perceived by the participant as being more useful. CONCLUSIONS: The evaluation of context-sensitive systems that overlap into domestic lives is challenging. We believe that the ideal experiment is to deploy such systems in real homes and assess performance longitudinally. This case study in an instrumented live-in facility is a step toward that long-term goal.

Expression of CD44, E-cadherin, and antimetastatic protein nm23-H1 in complete hydatidiform moles.

INTRODUCTION: There is scant information about the expression of CD44 and E-cadherin, two cell adhesion molecules, and the antimetastatic protein nm23-H1, in complete hydatidiform moles. We measured the expression of these markers to determine their usefulness in predicting the development of invasive disease. MATERIALS AND METHODS: We performed a retrospective study of 27 patients with complete hydatidiform moles, collecting clinical information including the patient's age, pre-evacuation hCG level, pathology, hCG monitoring, and the development of gestational trophoblastic neoplasia. Immunohistochemical staining for CD44, E-cadherin, and nm23-H1 was performed. CD44 expression was classified as positive or negative. For E-cadherin and nm23-H1, the intensity of expression was graded on a 0 to 3 scale. Chi-square or Fisher's exact testing was used to evaluate the relationship between these markers and the development of invasive disease. RESULTS: CD44 was expressed in 26% of cases. E-cadherin expression was 1+, 2+, and 3+in 8%, 33%, and 59% of cases, respectively. Nm23-H1 expression was 1+, 2+, and 3+in 4%, 11%, and 85% of cases. The risk of developing invasive disease did not correlate with the expression of CD44, E-cadherin, or nm23-H1. CONCLUSION: In this preliminary study, there is no relationship between CD44, E-cadherin, and nm23-H1 expression in complete hydatidiform moles and the risk of invasive disease. Other molecular markers predictive of invasive disease should be sought to limit hCG surveillance to those at risk.

Earthquake nucleation by transient deformations caused by the M = 7.9 Denali, Alaska, earthquake.

The permanent and dynamic (transient) stress changes inferred to trigger earthquakes are usually orders of magnitude smaller than the stresses relaxed by the earthquakes themselves, implying that triggering occurs on critically stressed faults. Triggered seismicity rate increases may therefore be most likely to occur in areas where loading rates are highest and elevated pore pressures, perhaps facilitated by high-temperature fluids, reduce frictional stresses and promote failure. Here we show that the 2002 magnitude M = 7.9 Denali, Alaska, earthquake triggered widespread seismicity rate increases throughout British Columbia and into the western United States. Dynamic triggering by seismic waves should be enhanced in directions where rupture directivity focuses radiated energy, and we verify this using seismic and new high-sample GPS recordings of the Denali mainshock. These observations are comparable in scale only to the triggering caused by the 1992 M = 7.4 Landers, California, earthquake, and demonstrate that Landers triggering did not reflect some peculiarity of the region or the earthquake. However, the rate increases triggered by the Denali earthquake occurred in areas not obviously tectonically active, implying that even in areas of low ambient stressing rates, faults may still be critically stressed and that dynamic triggering may be ubiquitous and unpredictable.

Role of endoscopic retrograde cholangiopancreatography in the management of suspected choledocholithiasis.

BACKGROUND: Indications for endoscopic retrograde cholangiopancreatography (ERCP) are not precisely defined. With the increasing availability of magnetic resonance cholangiopancreatography (MRCP) and several prospective studies proving the accuracy of this modality, it is important to select appropriate criteria for invasive testing when common bile duct (CBD) pathology is suspected. METHODS: We reviewed 200 consecutive ERCPs performed for jaundice, pancreatitis, noninvasive visualization of CBD stones, radiologic evidence of CBD dilatation, elevated liver function tests, or biliary colic. Diagnostic and therapeutic yields are determined for each indication and various combinations thereof. RESULTS: Of the 180 ERCPs performed for suspected choledocholithiasis, 97 (53.8%) were performed for multiple indications, whereas 83 (46.2%) were performed for only one indication. One hundred two patients (56.6%) had CBD pathology, whereas 78 explorations (43.4%) were negative. If multiple indications for ERCP were present, the diagnostic yield was 85.6%. When there was only one indication, the diagnostic yield decreased to 25.3%. CONCLUSIONS: ERCP is an invasive procedure with significant morbidity that should be used selectively. MRCP may be a more appropriate initial evaluation of suspected CBD pathology in many patients.

Present-day crustal deformation in China constrained by global positioning system measurements.

Global Positioning System (GPS) measurements in China indicate that crustal shortening accommodates most of India's penetration into Eurasia. Deformation within the Tibetan Plateau and its margins, the Himalaya, the Altyn Tagh, and the Qilian Shan, absorbs more than 90% of the relative motion between the Indian and Eurasian plates. Internal shortening of the Tibetan plateau itself accounts for more than one-third of the total convergence. However, the Tibetan plateau south of the Kunlun and Ganzi-Mani faults is moving eastward relative to both India and Eurasia. This movement is accommodated through rotation of material around the eastern Syntaxis. The North China and South China blocks, east of the Tibetan Plateau, move coherently east-southeastward at rates of 2 to 8 millimeters per year and 6 to 11 millimeters per year, respectively, with respect to the stable Eurasia.

Soybean genomic survey: BAC-end sequences near RFLP and SSR markers.

We are building a framework physical infrastructure across the soybean genome by using SSR (simple sequence repeat) and RFLP (restriction fragment length polymorphism) markers to identify BACs (bacterial artificial chromosomes) from two soybean BAC libraries. The libraries were prepared from two genotypes, each digested with a different restriction enzyme. The BACs identified by each marker were grouped into contigs. We have obtained BAC- end sequence from BACs within each contig. The sequences were analyzed by the University of Minnesota Center for Computational Genomics and Bioinformatics using BLAST algorithms to search nucleotide and protein databases. The SSR-identified BACs had a higher percentage of significant BLAST hits than did the RFLP-identified BACs. This difference was due to a higher percentage of hits to repetitive-type sequences for the SSR-identified BACs that was offset in part, however, by a somewhat larger proportion of RFLP-identified significant hits with similarity to experimentally defined genes and soybean ESTs (expressed sequence tags). These genes represented a wide range of metabolic functions. In these analyses, only repetitive sequences from SSR-identified contigs appeared to be clustered. The BAC-end sequences also allowed us to identify microsynteny between soybean and the model plants Arabidopsis thaliana and Medicago truncatula. This map-based approach to genome sampling provides a means of assaying soybean genome structure and organization.