Randomized phase III trial of piroxicam in combination with mitoxantrone or carboplatin for first-line treatment of urogenital tract transitional cell carcinoma in dogs.

BackgroundReported response rates of transitional cell carcinoma (TCC) in dogs to piroxicam in combination with either mitoxantrone or carboplatin are similar; however, it is unknown whether either drug might provide superior duration of response.Hypothesis/objectivesTo determine if the progression-free interval (PFI) of dogs with TCC treated with mitoxantrone and piroxicam was different than that of dogs receiving carboplatin and piroxicam. The hypothesis was that the efficacy of mitoxantrone is no different from carboplatin.AnimalsFifty dogs with TCC without azotemia.MethodsProspective open-label phase III randomized study. Either mitoxantrone or carboplatin was administered every 3 weeks concurrently with piroxicam with restaging at 6-week intervals. Twenty-four dogs received carboplatin and 26 received mitoxantrone.ResultsResponse was not different between groups (P = .56). None of the dogs showed complete response. In the mitoxantrone group, there were 2 (8%) partial responses (PR) and 18 (69%) dogs with stable disease (SD). In the carboplatin group, there were 3 PR (13%) and 13 (54%) dogs with SD. The PFI was not significantly different between groups (mitoxantrone = 106 days; carboplatin = 73.5 days; P = .62; hazard ratio 0.86; 95% confidence interval 0.47-1.56). Dogs with prostatic involvement experienced a shorter survival (median, 109 days) compared to dogs with urethral, trigonal, or apically located tumors; this difference was significant (median 300, 190, and 645 days, respectively; P = .005).Conclusions and clinical importanceThis study did not detect a different in outcome in dogs with TCC treated with either mitoxantrone or carboplatin in combination with piroxicam

Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.

BackgroundCompounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products.Hypothesis/objectivesThe initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies.AnimalsThirty-seven dogs treated with FDA-approved or compounded lomustine.MethodsDogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection.ResultsTwenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration.Conclusions and clinical importanceThese data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products

Seasonal Cycles of Phytoplankton and Net Primary Production from Biogeochemical Argo Float Data in the South-West Pacific Ocean

We present annual cycles of chlorophyll a, phytoplankton carbon, nitrate and oxygen for Subtropical (STW), Subantarctic (SAW), and Subantarctic Mode (SAMW) waters near Aotearoa New Zealand from data collected by two Biogeochemical (BGC) Argo floats. We develop two simple models of depth-integrated net primary production (NPP), tuned against 14C-uptake measurements, to compare with Vertically-Generalised Production Model (VGPM) satellite-based estimates of NPP. One model is the simplest possible, and assumes production is proportional to light multiplied by chlorophyll a concentration. The second model modifies the light response profile to account for photoacclimation. In STW at 30–35°S, enhanced production is initiated in austral autumn when the mixed layer deepens to entrain nutrients into the photic zone. For about half the year, there is substantial production within a deep chlorophyll maximum that sits below the mixed layer. Consequently, depth-integrated NPP is only loosely related to surface biomass as imaged from satellite remote-sensing, and BGC Argo-based model estimates of depth-integrated NPP are about double VGPM estimates. In SAW at 45–55°S, production is initiated when vertical mixing decreases in austral spring. Production is largely within the mixed layer, and depth-integrated phytoplankton biomass and depth-integrated NPP follow surface phytoplankton biomass. Model estimates of depth-integrated NPP based on BGC Argo float profiles are comparable with VGPM estimates for the southern water masses

Impact of Mesoporous Silicon Template Pore Dimension and Surface Chemistry on Methylammonium Lead Trihalide Perovskite Photophysics

© 2020 Wiley-VCH GmbH In influencing fundamental properties—and ultimately device performance—of lead halide perovskites, interfacial interactions play a major role, notably with regard to carrier diffusion and recombination. Here anodized porous Si (pSi) as well as porous silica particles are employed as templates for formation of methylammonium lead trihalide nanostructures. This allows synthesis of relatively small perovskite domains and comparison of associated interfacial chemistry between as-prepared hydrophobic hydrideterminated functionalities and hydrophilic oxide-terminated surfaces. While physical confinement of MAPbBr3 has a uniform effect on carrier lifetime, pore size (7–18 nm) of the silicon-containing template has a sensitive influence on perovskite photoluminescence (PL) wavelength maximum. Furthermore, identity of the surface functionality of the template significantly alters the PL quantum efficiency, with lowest PL intensity associated with the H-terminated pSi and the most intense PL affiliated with the oxideterminated pSi surface. These effects are explored for green-emitting MAPbBr3 as well as infrared-emitting MAPbI3. In addition, the role of silicon surface chemistry on the time-dependent stability of these perovskites packaged within a given mesoporous template is also evaluated, specifically, a lack of miscibility between MAPbI3 and the H-terminated pSi template results in a diffusion of this specific perovskite composition eluting from this porous matrix over time

Tuberculosis Incidence Rates during 8 Years of Follow-Up of an Antiretroviral Treatment Cohort in South Africa: Comparison with Rates in the Community

BACKGROUND: Although antiretroviral therapy (ART) is known to be associated with time-dependent reductions in tuberculosis (TB) incidence, the long-term impact of ART on incidence remains imprecisely defined due to limited duration of follow-up and incomplete CD4 cell count recovery in existing studies. We determined TB incidence in a South African ART cohort with up to 8 years of follow-up and stratified rates according to CD4 cell count recovery. We compared these rates with those of HIV-uninfected individuals living in the same community. METHODOLOGY/PRINCIPAL FINDINGS: Prospectively collected clinical data on patients receiving ART in a community-based cohort in Cape Town were analysed. 1544 patients with a median follow-up of 5.0 years (IQR 2.4-5.8) were included in the analysis. 484 episodes of incident TB (73.6% culture-confirmed) were diagnosed in 424 patients during 6506 person-years (PYs) of follow-up. The TB incidence rate during the first year of ART was 12.4 (95% CI 10.8-14.4) cases/100PYs and decreased to 4.92 (95% CI 3.64-8.62) cases/100PYs between 5 and 8 years of ART. During person-time accrued within CD4 cell strata 0-100, 101-200, 201-300, 301-400, 401-500, 501-700 and ≥700 cells/µL, TB incidence rates (95% CI) were 25.5 (21.6-30.3), 11.2 (9.4-13.5), 7.9 (6.4-9.7), 5.0 (3.9-6.6), 5.1 (3.8-6.8), 4.1 (3.1-5.4) and 2.7 (1.7-4.5) cases/100PYs, respectively. Overall, 75% (95% CI 70.9-78.8) of TB episodes were recurrent cases. Updated CD4 cell count and viral load measurements were independently associated with long-term TB risk. TB rates during person-time accrued in the highest CD4 cell count stratum (>700 cells/µL) were 4.4-fold higher that the rate in HIV uninfected individuals living in the same community (2.7 versus 0.62 cases/100PYs; 95%CI 0.58-0.65). CONCLUSIONS/SIGNIFICANCE: TB rates during long-term ART remained substantially greater than rates in the local HIV uninfected populations regardless of duration of ART or attainment of CD4 cell counts exceeding 700 cells/µL

A longitudinal study of risk factors for the occurrence, duration and severity of menstrual cramps in a cohort of college women

To describe how menstrual cramps vary from cycle to cycle within a woman over time. To examine the influence of weight and lifestyle factors on occurrence, duration, and severity of menstrual pain. Design A one-year prospective menstrual diary study. Participants One hundred and sixty-five women aged 17 to 19 years entering a local university in 1985. Main outcome measures The occurrence, length, and maximum severity of pain during a menstrual period. Results Menstrual pain occurred during 71.6% of observed menstrual bleeds, most commonly beginning the first day of menses. The median duration was two days. Sixty percent of women reported at least one episode of severe pain, while 13% reported severe pain more than half the time. Earlier age at menarche and long menstrual periods increased the occurrence, duration and severity of pain. In smokers, cramps tended to last longer. Being overweight was an important risk factor for menstrual cramps and doubled the odds of having a long pain episode. Frequent alcohol consumption decreased the probability of having menstrual cramps, but in women who had pain it increased duration and severity. Physical activity was not associated with any pain parameter. Conclusions Women who have pain lasting three days are an important target group for prophylactic therapy. The occurrence and severity of menstrual cramps is influenced by potentially modifiable characteristics including weight, smoking, and alcohol consumption. Doctors may wish to counsel women presenting with dysmenorrhoea about the importance of healthy lifestyles and about the inefficacy of alcohol consumption as a treatment for dysmenorrhoea.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73220/1/j.1471-0528.1996.tb09597.x.pd

Comparing ‘Twitter’ polls results with an online survey on surgeons perspectives for the treatment of rectal cancer

INTRODUCTION: Traditional surveys (including phone, mail and online) can be valuable tools to obtain information from specific communities. Social media apps such as Twitter are being increasingly adopted for knowledge dissemination and research purposes. Twitter polls are a unique feature which allows for a rapid response to questions posed. Nonetheless Twitter does not constitute a validated survey technique. The objective was to compare the similarities of Twitter polls in describing practice patterns for the treatment of rectal cancer. METHODS: A survey on the management of rectal cancer was designed using modified Delphi methodology. Surgeons were contacted through major colorectal societies to participate in an online survey. The same set of questions were periodically posted by influencers on Twitter polls and the results were compared. RESULTS: A total of 753 surgeons participated in the online survey. Individual participation in Twitter ranged from 162 to 463 responses. There was good and moderate agreement between the two methods for the most popular choice (9/10) and the least popular choice (5/10), respectively. DISCUSSION: It is possible that in the future polls available via social media can provide a low-cost alternative and an efficient, yet pragmatic method to describe clinical practice patterns. This is the first study comparing Twitter polls with a traditional survey method in medical research. CONCLUSIONS: There is viable opportunity to enhance the performance of research through social media, however, significant refinement is required. These results can potentially be transferable to other areas of medicine

Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction

Traumatic fracture-dislocation of the hip following rugby tackle: a case report

Posterior fracture-dislocation of hip is uncommonly encountered in rugby injuries. We report such a case in an adult while playing rugby. The treating orthopaedician can be caught unaware and injuries in such sports can be potentially misdiagnosed as hip sprains. Immediate reduction of the dislocation was performed in theatres. The fracture was fixed with two lag screws and a neutralization plate. This led to early rehabilitation and speedy recovery with return to sporting activities by 12 months

Surface and Temporal Biosignatures

Recent discoveries of potentially habitable exoplanets have ignited the prospect of spectroscopic investigations of exoplanet surfaces and atmospheres for signs of life. This chapter provides an overview of potential surface and temporal exoplanet biosignatures, reviewing Earth analogues and proposed applications based on observations and models. The vegetation red-edge (VRE) remains the most well-studied surface biosignature. Extensions of the VRE, spectral "edges" produced in part by photosynthetic or nonphotosynthetic pigments, may likewise present potential evidence of life. Polarization signatures have the capacity to discriminate between biotic and abiotic "edge" features in the face of false positives from band-gap generating material. Temporal biosignatures -- modulations in measurable quantities such as gas abundances (e.g., CO2), surface features, or emission of light (e.g., fluorescence, bioluminescence) that can be directly linked to the actions of a biosphere -- are in general less well studied than surface or gaseous biosignatures. However, remote observations of Earth's biosphere nonetheless provide proofs of concept for these techniques and are reviewed here. Surface and temporal biosignatures provide complementary information to gaseous biosignatures, and while likely more challenging to observe, would contribute information inaccessible from study of the time-averaged atmospheric composition alone.Comment: 26 pages, 9 figures, review to appear in Handbook of Exoplanets. Fixed figure conversion error