Presynchronizing PGF2α and GnRH injections before timed artificial insemination CO-Synch + CIDR program

Fixed-time artificial insemination is an effective management tool that reduces the labor associated with more conventional artificial insemination programs requiring detection of estrus. The 7-day CO-Synch + controlled internal drug release (CIDR) insert protocol has been shown to effectively initiate estrus and ovulation in cycling and non-cycling suckled beef cows, producing pregnancy rates at or greater than 50% in beef cows. The gonadotropin-releasing hormone (GnRH) injection that begins the CO-Synch + CIDR program initiates ovulation in a large proportion of cows, particularly anestrous cows. The CIDR, which releases progesterone intravaginally, prevents short estrous cycles that usually follow the first postpartum ovulation in beef cows. Our hypothesis was that inducing estrus with a prostaglandin injection followed 3 days later with a GnRH injection, 7 days before applying the 7-day CO-Synch + CIDR protocol, might increase the percentage of cycling cows that would exhibit synchronous follicular waves after the onset of the CO-Synch + CIDR protocol. We also hypothesized that the additional GnRH injection would increase the percentage of anestrous cows that would ovulate, thereby increasing pregnancy outcomes

Spatial considerations during cryopreservation of a large volume sample

AbstractThere have been relatively few studies on the implications of the physical conditions experienced by cells during large volume (litres) cryopreservation – most studies have focused on the problem of cryopreservation of smaller volumes, typically up to 2 ml.This study explores the effects of ice growth by progressive solidification, generally seen during larger scale cryopreservation, on encapsulated liver hepatocyte spheroids, and it develops a method to reliably sample different regions across the frozen cores of samples experiencing progressive solidification.These issues are examined in the context of a Bioartificial Liver Device which requires cryopreservation of a 2 L volume in a strict cylindrical geometry for optimal clinical delivery. Progressive solidification cannot be avoided in this arrangement. In such a system optimal cryoprotectant concentrations and cooling rates are known. However, applying these parameters to a large volume is challenging due to the thermal mass and subsequent thermal lag. The specific impact of this to the cryopreservation outcome is required.Under conditions of progressive solidification, the spatial location of Encapsulated Liver Spheroids had a strong impact on post-thaw recovery. Cells in areas first and last to solidify demonstrated significantly impaired post-thaw function, whereas areas solidifying through the majority of the process exhibited higher post-thaw outcome. It was also found that samples where the ice thawed more rapidly had greater post-thaw viability 24 h post-thaw (75.7 ± 3.9% and 62.0 ± 7.2% respectively).These findings have implications for the cryopreservation of large volumes with a rigid shape and for the cryopreservation of a Bioartificial Liver Device

A combination intervention strategy to improve linkage to and retention in HIV care following diagnosis in Mozambique: A cluster-randomized study

Background: Concerning gaps in the HIV care continuum compromise individual and population health. We evaluated a combination intervention strategy (CIS) targeting prevalent barriers to timely linkage and sustained retention in HIV care in Mozambique. Methods and findings: In this cluster-randomized trial, 10 primary health facilities in the city of Maputo and Inhambane Province were randomly assigned to provide the CIS or the standard of care (SOC). The CIS included point-of-care CD4 testing at the time of diagnosis, accelerated ART initiation, and short message service (SMS) health messages and appointment reminders. A pre–post intervention 2-sample design was nested within the CIS arm to assess the effectiveness of CIS+, an enhanced version of the CIS that additionally included conditional non-cash financial incentives for linkage and retention. The primary outcome was a combined outcome of linkage to care within 1 month and retention at 12 months after diagnosis. From April 22, 2013, to June 30, 2015, we enrolled 2,004 out of 5,327 adults ≥18 years of age diagnosed with HIV in the voluntary counseling and testing clinics of participating health facilities: 744 (37%) in the CIS group, 493 (25%) in the CIS+ group, and 767 (38%) in the SOC group. Fifty-seven percent of the CIS group achieved the primary outcome versus 35% in the SOC group (relative risk [RR]CIS vs SOC = 1.58, 95% CI 1.05–2.39). Eighty-nine percent of the CIS group linked to care on the day of diagnosis versus 16% of the SOC group (RRCIS vs SOC = 9.13, 95% CI 1.65–50.40). There was no significant benefit of adding financial incentives to the CIS in terms of the combined outcome (55% of the CIS+ group achieved the primary outcome, RRCIS+ vs CIS = 0.96, 95% CI 0.81–1.16). Key limitations include the use of existing medical records to assess outcomes, the inability to isolate the effect of each component of the CIS, non-concurrent enrollment of the CIS+ group, and exclusion of many patients newly diagnosed with HIV. Conclusions: The CIS showed promise for making much needed gains in the HIV care continuum in our study, particularly in the critical first step of timely linkage to care following diagnosis

Discovery of New Ultracool White Dwarfs in the Sloan Digital Sky Survey

We report the discovery of five very cool white dwarfs in the Sloan Digital Sky Survey (SDSS). Four are ultracool, exhibiting strong collision induced absorption (CIA) from molecular hydrogen and are similar in color to the three previously known coolest white dwarfs, SDSS J1337+00, LHS 3250 and LHS 1402. The fifth, an ultracool white dwarf candidate, shows milder CIA flux suppression and has a color and spectral shape similar to WD 0346+246. All five new white dwarfs are faint (g > 18.9) and have significant proper motions. One of the new ultracool white dwarfs, SDSS J0947, appears to be in a binary system with a slightly warmer (T_{eff} ~ 5000K) white dwarf companion.Comment: 15 pages, 3 figures, submitted to ApJL. Higher resolution versions of finding charts are available at http://astro.uchicago.edu/~gates/findingchart

Implementing exercise in cancer care: study protocol to evaluate a community-based exercise program for people with cancer

Background Clinical research has established the efficacy of exercise in reducing treatment-related side-effects and increasing wellbeing in people with cancer. Major oncology organisations have identified the importance of incorporating exercise in comprehensive cancer care but information regarding effective approaches to translating evidence into practice is lacking. This paper describes the implementation of a community-based exercise program for people with cancer and the protocol for program evaluation. Methods/Design The Life Now Exercise program is a community-based exercise intervention designed to mitigate and rehabilitate the adverse effects of cancer and its treatment and improve physical and psychosocial wellbeing in people with cancer. Involvement in the program is open to people with any diagnosis of cancer who are currently receiving treatment or within 2 years of completing treatment. The 3-month intervention consists of twice weekly group-based exercise sessions administered in community exercise clinics under the supervision of exercise physiologists trained to deliver the program. Evaluation of the program involves measures of uptake, safety, adherence and effectiveness (including cost effectiveness) as assessed at the completion of the program and 6 months follow-up. Discussion To bridge the gap between research and practice, the Life Now Exercise program was designed and implemented to provide people with cancer access to evidence-based exercise medicine. The framework for program implementation and evaluation offers insight into the development of feasible, generalizable and sustainable supportive care services involving exercise. Community-based exercise programs specifically designed for people with cancer are necessary to facilitate adherence to international guidelines advising patients to participate in high-quality exercise

Validation of Envisat MERIS algorithms for chlorophyll retrieval in a large, turbid and optically-complex shallow lake

The 10-year archive of MEdium Resolution Imaging Spectrometer (MERIS) data is an invaluable resource for studies on lake system dynamics at regional and global scales. MERIS data are no longer actively acquired but their capacity for global scale monitoring of lakes from satellites will soon be re-established through the forthcoming Sentinel-3 Ocean and Land Colour Instrument (OLCI). The development and validation of in-water algorithms for the accurate retrieval of biogeochemical parameters is thus of key importance if the potential of MERIS and OLCI data is to be fully exploited for lake monitoring. This study presents the first extensive validation of algorithms for chlorophyll-a (chl-a) retrieval by MERIS in the highly turbid and productive waters of Lake Balaton, Hungary. Six algorithms for chl-a retrieval from MERIS over optically complex Case 2 waters, including band-difference and neural network architectures, were compared using the MERIS archive for 2007-2012. The algorithms were locally-tuned and validated using in situ chl-a data (n = 289) spanning the five year processed image time series and from all four lake basins. In general, both band-difference algorithms tested (Fluorescence Line Height (FLH) and Maximum Chlorophyll Index (MCI)) performed well, whereas the neural network processors were generally found to much less accurately retrieve in situ chl-a concentrations. The Level 1b FLH algorithm performed best overall in terms of chl-a retrieval (R2 = 0.87; RMSE = 4.19 mg m- 3; relative RMSE = 30.75%) and particularly at chl-a concentrations of ≥ 10 mg m- 3 (R2 = 0.85; RMSE = 4.81 mg m- 3; relative RMSE = 20.77%). However, under mesotrophic conditions (i.e., chl-a < 10 mg m- 3) FLH was outperformed by the locally-tuned FUB/WeW processor (relative FLH RMSE < 10 mg m- 3 = 57.57% versus relative FUB/WeW RMSE < 10 mg m- 3 = 46.96%). An ensemble selection of in-water algorithms is demonstrated to improve chl-a retrievals

Safety and feasibility of prostate stereotactic ablative radiotherapy using multi-modality imaging and flattening filter free

OBJECTIVE: To investigate feasibility and safety of stereotactic ablative radiotherapy in the management of prostate cancer while employing MR/CT fusion for delineation, fiducial marker seeds for positioning and Varian RapidArc with flattening filter free (FFF) delivery. METHODS: 41 patients were treated for low-intermediate risk prostate cancer with initial prostate-specific antigen of ≤20 ng ml−1, Gleason score 6–7. Patients had MR/CT fusion for delineation of prostate ±seminal vesicles. CT/MR fusion images were used for delineation and planned using flattening filter free modality. Verification on treatment was cone beam CT imaging with fiducial markers for matching. Patients had Radiation Therapy Oncology Group scoring for genitourinary and gastointestinal symptoms at baseline, week 4, 10 and 18. RESULTS: Clinically acceptable plans were achieved for all patients, all plans achieved the objective clinical target volume D99% ≥ 95%, and for planning target volume D95% ≥ 95%. Rectum dose constraints were met for 95.1% for V18 Gy ≤ 35%, 80% V28 Gy ≤ 10%. A total of 32 (78.0%) plans achieved all rectum dose constraints. Grade 1 acute genitourinary symptoms were 53.7% of patients at baseline, 90.2% [95% CI (76.8–97.3%)] (p = 0.0005) at treatment 5, falling to 78.0% (62.4–89.4%) at week 4, and 75.0% (58.8–87.3%) by week 10 and 52.5% (36.1–68.5%) (p = 1.00) at week 18. Acute gastrointestinal symptoms were 5% at baseline, 46.3% [95% CI (30.7–62.6%)] at treatment 5, week 4 43.9% [95% CI (28.5–60.3%)], week 10 25.0% (11.1–42.3%), and declined slightly by week 18 [–20.095% CI (12.7–41.2)] p = 0.039. Overall 75.6% (31/41) of patients experienced Grade 1–2 toxicity during or after treatment. CONCLUSION: This planning and delivery technique is feasible, safe and efficient. A homogeneous dose can be delivered to prostate with confidence, whilst limiting high dose to nearby structures. The use of this technology can be applied safely within further randomized study protocols

Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Hemoglobinopathies Using a Reduced-Intensity Conditioning Regimen and Third-Party Mesenchymal Stromal Cells

AbstractAllogeneic hematopoietic stem cell transplantation for patients with a hemoglobinopathy can be curative but is limited by donor availability. Although positive results are frequently observed in those with an HLA-matched sibling donor, use of unrelated donors has been complicated by poor engraftment, excessive regimen-related toxicity, and graft-versus-host disease (GVHD). As a potential strategy to address these obstacles, a pilot study was designed that incorporated both a reduced-intensity conditioning and mesenchymal stromal cells (MSCs). Six patients were enrolled, including 4 with high-risk sickle cell disease (SCD) and 2 with transfusion-dependent thalassemia major. Conditioning consisted of fludarabine (150 mg/m2), melphalan (140 mg/m2), and alemtuzumab (60 mg for patients weighing > 30 kg and .9 mg/kg for patients weighing <30 kg). Two patients received HLA 7/8 allele matched bone marrow and 4 received 4-5/6 HLA matched umbilical cord blood as the source of HSCs. MSCs were of bone marrow origin and derived from a parent in 1 patient and from an unrelated third-party donor in the remaining 5 patients. GVHD prophylaxis consisted of cyclosporine A and mycophenolate mofetil. One patient had neutropenic graft failure, 2 had autologous hematopoietic recovery, and 3 had hematopoietic recovery with complete chimerism. The 2 SCD patients with autologous hematopoietic recovery are alive. The remaining 4 died either from opportunistic infection, GVHD, or intracranial hemorrhage. Although no infusion-related toxicity was seen, the cotransplantation of MSCs was not sufficient for reliable engraftment in patients with advanced hemoglobinopathy. Although poor engraftment has been observed in nearly all such trials to date in this patient population, there was no evidence to suggest that MSCs had any positive impact on engraftment. Because of the lack of improved engraftment and unacceptably high transplant-related mortality, the study was prematurely terminated. Further investigations into understanding the mechanisms of graft resistance and development of strategies to overcome this barrier are needed to move this field forward