Search

Objective: The relationship between atrial fibrillation (AF) and heart failure with depressed ejection fraction (EF) is complex. AF-related tachycardia-mediated cardiomyopathy (TMC) can lead to worsening EF and clinical heart failure. We sought to determine whether a hybrid team ablation approach (HA) can be performed safely and restore normal sinus rhythm in patients with TMC and heart failure and to delineate the effect on heart failure. Methods: We retrospectively analyzed patients with nonparoxysmal (ie, persistent and long-standing persistent) AF-related TMC with depressed left ventricular EF (LVEF ≤40%) and heart failure (New York Heart Association [NYHA] class ≥2) who underwent HA between 2013 and 2018 and had at least 1 year of follow-up. Pre-HA and post-HA echocardiograms were compared for LVEF and left atrial (LA) size. Rhythm success was defined as 60% of patients during a mean 3.5 ± 1.9 years of follow-up. LVEF improved significantly by 12.0% ± 12.5% (95% CI, 7.85%-16.0%; P

Extracts from Euglena gracilis have been shown to prevent cancer growth in mouse models. However, the molecular mechanism of this anti-cancer activity has not been determined nor has the effect of Euglena extracts on tobacco smoke carcinogen-induced carcinogenesis. Here, we investigate the hypothesis that this anti-cancer activity is a result of changes in the intestinal microbiota induced by oral administration of the extract. We found that a Euglena gracilis water extract prevents lung tumorigenesis induced by a tobacco smoke-specific carcinogen (NNK) in mice treated either 2 weeks before or 10 weeks after NNK injection. Both of these treatment regimens are associated with significant increases in 27 microbiota metabolites found in the mouse feces, including large increases in triethanolamine, salicylate, desaminotyrosine, N-acetylserine, glycolate, and aspartate. Increases in the short-chain fatty acids (SCFAs) including acetate, propionate and butyrate are also observed. We also detected a significant attenuation of lung carcinoma cell growth through the induction of cell cycle arrest and apoptosis caused by low levels of SCFAs. This study provides strong evidence of anti-cancer activity in Euglena gracilis extracts against tobacco smoke carcinogen-induced tumorigenesis and demonstrates that this activity is linked to increased production of specific gut microbiota metabolites and the resultant induction of cell cycle arrest and apoptosis of lung carcinoma cells.

OBJECTIVE:. Prolonged cardiac arrest (CA) causes microvascular thrombosis which is a potential barrier to organ reperfusion during extracorporeal cardiopulmonary resuscitation (ECPR). The aim of this study was to test the hypothesis that early intra-arrest anticoagulation during cardiopulmonary resuscitation (CPR) and thrombolytic therapy during ECPR improve recovery of brain and heart function in a porcine model of prolonged out-of-hospital CA. DESIGN:. Randomized interventional trial. SETTING:. University laboratory. SUBJECTS:. Swine. INTERVENTIONS:. In a blinded study, 48 swine were subjected to 8 minutes of ventricular fibrillation CA followed by 30 minutes of goal-directed CPR and 8 hours of ECPR. Animals were randomized into four groups (n = 12) and given either placebo (P) or argatroban (ARG; 350 mg/kg) at minute 12 of CA and either placebo (P) or streptokinase (STK, 1.5 MU) at the onset of ECPR. MEASUREMENTS AND MAIN RESULTS:. Primary outcomes included recovery of cardiac function measured by cardiac resuscitability score (CRS: range 0–6) and recovery of brain function measured by the recovery of somatosensory-evoked potential (SSEP) cortical response amplitude. There were no significant differences in recovery of cardiac function as measured by CRS between groups (p = 0.16): P + P 2.3 (1.0); ARG + P = 3.4 (2.1); P + STK = 1.6 (2.0); ARG + STK = 2.9 (2.1). There were no significant differences in the maximum recovery of SSEP cortical response relative to baseline between groups (p = 0.73): P + P = 23% (13%); ARG + P = 20% (13%); P + STK = 25% (14%); ARG + STK = 26% (13%). Histologic analysis demonstrated reduced myocardial necrosis and neurodegeneration in the ARG + STK group relative to the P + P group. CONCLUSIONS:. In this swine model of prolonged CA treated with ECPR, early intra-arrest anticoagulation during goal-directed CPR and thrombolytic therapy during ECPR did not improve initial recovery of heart and brain function but did reduce histologic evidence of ischemic injury. The impact of this therapeutic strategy on the long-term recovery of cardiovascular and neurological function requires further investigation.

Background The US Veterans Health Administration (VA) is transforming its healthcare system to create a Whole Health System (WHS) of care. Akin to such reorganization efforts as creating patient-centered medical homes and primary care behavioral health integration, the WHS goes beyond by transforming the entire system to one that takes a proactive approach to support patient and employee health and wellness. The SARS-CoV-2 pandemic disrupted the VA’s healthcare system and added stress for staff and patients, creating an exogenous shock for this transformation towards a WHS. Objective We examined the relationship between VA’s WHS transformation and the pandemic to understand if transformation was sustained during crisis and contributed to VA’s response. Methods Qualitative interviews were conducted as part of a multi-year study of WHS transformation. A single multi-person interview was conducted with 61 WHS leaders at 18 VA Medical Centers, examining WH transformation and use during the pandemic. Data were analyzed using rapid directed content analysis. Results While the pandemic initially slowed transformation efforts, sites intentionally embraced a WH approach to support patients and employees during this crisis. Efforts included conducting patient wellness calls, and, for patients and employees, promoting complementary and integrative health therapies, self-care, and WH concepts to combat stress and support wellbeing. A surge in virtual technology use facilitated innovative delivery of complementary and integrative therapies and promoted continued use of WH activities. Conclusion The pandemic called attention to the need for healthcare systems to address the wellbeing of both patients and providers to sustain high quality care delivery. At a time of crisis, VA sites sustained WH transformation efforts, recognizing WH as one strategy to support patients and employees. This response indicates cultural transformation is taking hold, with WH serving as a promising approach for promoting wellbeing among patients and employees alike.

As new alloys are being developed for additive manufacturing (AM) applications, questions related to the temperature-dependent structural and compositional stability of these alloys remain. In this work, the benefits and limitations of a unique method for testing this stability are presented. This system employs the use of polychromatic synchrotron light to perform energy-dispersive x-ray diffraction (ED-XRD) on an electrostatically levitated sample at high temperatures. In comparison with a traditional angular-dispersive setup, the container-less electrostatic levitation method has unique advantages, including quicker acquisition times, simultaneous compositional information through fluorescence emissions, a reduction in background noise, and, importantly, concurrent/subsequent measurement of thermophysical properties. This combined method is ideal for phase transition studies by holding the levitated sample at a stable position and temperature through controlled heating and temperature management. To illustrate these capabilities, we show ED-XRD data of the well-known martensitic phase transition (hcp to bcc) in Ti-6Al-4V. In addition, results from the novel alloy Ni51Cu44Cr5 are presented. This alloy is shown to maintain an fcc structure upon heating. However, the concentration of Cu is reduced at high temperatures, resulting in a decrease in the lattice constant. As concurrent thermophysical properties are probed, these preliminary structure and composition experiments demonstrate the capabilities of this technique to determine the composition-processing-structure-properties of metal alloys for AM., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

The current standard of care treatment for canine lymphoma is a multi-agent, CHOP-based chemotherapy protocol. Single agent doxorubicin (DOX) is less burdensome; however, multi-agent chemotherapy protocols are often superior. The recently approved drug rabacfosadine (RAB, Tanovea) provides an attractive option for combination therapy with DOX, as both drugs demonstrate efficacy against lymphoma and possess different mechanisms of action. A previous study evaluating alternating RAB/DOX reported an overall response rate (ORR) of 84%, with a median progression-free survival time (PFS) of 194 days. The aim of this prospective trial was to evaluate the same protocol in an additional population of dogs. Fifty-nine dogs with treatment naïve lymphoma were enrolled. RAB (1.0 mg/kg IV) was alternated with DOX (30 mg/m 2 IV) every 21 days for up to six total treatments (3 cycles). Response assessment and adverse event (AE) evaluation were performed every 21 days using VCOG criteria. The ORR was 93% (79% CR, 14% PR). The median time to maximal response was 21.5 days; median PFS was 199 days. T cell immunophenotype and lack of treatment response were predictive of inferior outcomes. AEs were mostly gastrointestinal. Six dogs developed presumed or confirmed pulmonary fibrosis; four were grade 5. One dog experienced grade 3 extravasation injury with RAB that resolved with supportive treatment. These data mirror those of the previously reported RAB/DOX study, and support the finding that alternating RAB/DOX is a reasonable treatment option for canine lymphoma., (© 2024 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Establishing and proving methodological rigor has long been a challenge for qualitative researchers where quantitative methods prevail, but much published literature on qualitative analysis assumes a relatively small number of researchers working in relative proximity. This is particularly true for research conducted with a grounded theory approach. Different versions of grounded theory are commonly used, but this methodology was originally developed for a single researcher collecting and analyzing data in isolation. Although grounded theory has evolved since its development, little has been done to reconcile this approach with the changing nature and composition of international research teams. Advances in technology and an increased emphasis on transnational collaboration have facilitated a shift wherein qualitative datasets have been getting larger and the teams collecting and analyzing them more diverse and diffuse. New processes and systems are therefore required to respond to these conditions. Data for this article are drawn from the experiences of the Innovations for Choice and Autonomy (ICAN) Research Consortium. ICAN aims to understand how self-injectable contraceptives can be implemented in ways that best meet women's needs in Kenya, Uganda, Malawi, and Nigeria. We found that taking a structured approach to analysis was important for maintaining consistency and making the process more manageable across countries. However, it was equally important to allow for flexibility within this structured approach so that teams could adapt more easily to local conditions, making data collection and accompanying analysis more feasible. Meaningfully including all interested researchers in the analysis process and providing support for learning also increased rigor. However, competing priorities in a complex study made it difficult to adhere to planned timelines. We conclude with recommendations for both funders and study teams to design and conduct global health studies that ensure more equitable contributions to analysis while remaining logistically feasible and methodologically sound., (© Suchman et al.)

Objective: To assess the efficacy of oral low-level laser therapy (LLLT) - also known as photobiomodulation - in the reduction of oral mucositis experienced by children and young people with cancer undergoing chemotherapy., Design: A systematic review to evaluate the efficacy of oral LLLT for oral mucositis in children with cancer and the safety of oral LLLT in any age with cancer (International Prospective Register of Systematic Reviews/PROSPERO registration: CRD42018099772). Multiple databases and grey literature were screened. Randomised controlled trials were considered for assessing efficacy, and all studies were considered for assessing safety. Primary outcomes included severity of oral mucositis, oral pain and adverse events. Where results were compatible, meta-analysis was performed using a random-effects model. A narrative synthesis considered other outcome measures., Results: 14 studies (n>416 children) were included in the narrative synthesis of LLLT efficacy. 5 studies (n=380 children and young people) were included in the meta-analyses. Results demonstrate that LLLT may reduce the severity of oral mucositis and the level of oral pain, but further randomised controlled trials are needed to confirm or deny this. There is vast variation in different trial protocols. Insufficient blinding between LLLT or sham therapy/control led to a strong risk of performance bias. 75 studies (encompassing 2712 patients of all ages who had undergone LLLT) demonstrated minor and infrequent adverse reactions, but most studies had significant areas of weakness in quality., Conclusion: LLLT appears to be a safe therapy, but further evidence is needed to assess its efficacy as a prevention or treatment tool for oral mucositis in children with cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Rabacfosadine (RAB, Tanovea-CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs., Hypothesis/objectives: To determine the efficacy and safety of RAB in dogs with lymphoma., Animals: One hundred and fifty-eight client-owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019., Methods: Dogs were randomized to receive RAB or placebo at a 3 : 1 ratio. Treatment was given every 21 days for up to 5 treatments. Study endpoints included progression-free survival (PFS), overall response rate (ORR) at a given visit, best overall response rate (BORR), and percent progression free 1 month after treatment completion. Safety data were also collected., Results: The median PFS was significantly longer in the RAB group compared to placebo (82 vs 21 days; P < .0001, HR 6.265 [95% CI 3.947-9.945]). The BORR for RAB-treated dogs was 73.2% (50.9% complete response [CR], 22.3% partial response [PR]) and 5.6% (0% CR, 5.6% PR) for placebo-treated dogs (P < .0001). One month after the last treatment, 37 RAB-treated dogs (33%) were progression free compared with no placebo-treated dogs (P < .0001). The most common adverse events observed in the RAB group were diarrhea (87.5%), decreased appetite (68.3%), and vomiting (68.3%) and were generally low grade and reversible. Serious adverse events were reported in 24 RAB-treated (20%) and 5 placebo-treated dogs (13%)., Conclusions and Clinical Importance: Rabacfosadine demonstrated statistically significant antitumor efficacy in dogs with lymphoma when administered every 21 days for up to 5 treatments as compared to placebo., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

A 47-year-old woman with an implantable cardiac defibrillator and breast cancer underwent left breast mastectomy with simultaneous reconstruction using a breast tissue expander. She was found to have intermittent disabling of tachyarrhythmia detection and therapy functions of her implantable cardiac defibrillator that were triggered by the breast tissue expander magnetic port.

While it is mandated that reproductive and child health services be provided for free at public facilities in India, qualitative evidence suggests it is common for facilities to request bribes and other informal payments for medicines, medical tests or equipment. This article examines the prevalence of bribe requests, total out-of-pocket expenditures (OOPEs) and associations between bribe requests and total OOPEs on the experience of quality of care and maternal complications during childbirth. Women who delivered in public facilities in Uttar Pradesh, India were administered a survey on sociodemographic characteristics, bribe requests, total OOPEs, types of health checks received and experience of maternal complications. Data were analysed using descriptive, bivariate and multivariate statistics. Among the 2018 women who completed the survey, 43% were asked to pay a bribe and 73% incurred OOPEs. Bribe requests were associated with lower odds of receiving all health checks upon arrival to the facility (aOR = 0.49; 95% CI: 0.24-0.98) and during labour and delivery (aOR = 0.44; 95% CI: 0.25-0.76), lower odds of receiving most or all health checks after delivery (aOR = 0.44; 95% CI: 0.31-0.62) and higher odds of experiencing maternal complications (aOR = 1.45; 95% CI: 1.13-1.87). Although it is mandated that maternity care be provided for free in public facilities in India, these findings suggest that OOPEs are high, and bribes/tips contribute significantly. Interventions centred on improving person-centred care (particularly guidelines around bribes), health system conditions and women's expectations of care are needed., (© The Author(s) 2020. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: For a large trial of the effect of group antenatal care on perinatal outcomes in Rwanda, a Technical Working Group customized the group care model for implementation in this context. This process analysis aimed to understand the degree of fidelity with which the group antenatal care model was implemented during the trial period. Methods: We used two discreet questionnaires to collect data from two groups about the fidelity with which the group antenatal care model was implemented during this trial period. Group care facilitators recorded descriptive data about each visit and self-assessed process fidelity with a series of yes/no checkboxes. Master Trainers assessed process fidelity with an 11-item tool using a 5-point scale of 0 (worst) to 4 (best). Results: We analyzed 2763 questionnaires completed by group care facilitators that documented discreet group visits among pregnant and postnatal women and 140 questionnaires completed by Master Trainers during supervision visits. Data recorded by both groups was available for 84 group care visits, and we compared these assessments by visit. Approximately 80% of all group visits were provided as intended, with respect to both objective measures (e.g. group size) and process fidelity. We did not find reliable correlations between conceptually-related items scored by Master Trainers and self-assessment data reported by group visit facilitators. Conclusions: We recommend both the continued participation of expert observers at new and existing group care sites and ongoing self-assessment by group care facilitators. Finally, we present two abbreviated assessment tools developed by a Rwanda-specific Technical Working Group that reviewed these research results., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Butrick E et al.)

Objectives: To investigate stakeholder perspectives on how patient preference studies (PPS) should be designed and conducted to allow for inclusion of patient preferences in decision-making along the medical product life cycle (MPLC), and how patient preferences can be used in such decision-making. Methods: Two literature reviews and semi-structured interviews (n = 143) with healthcare stakeholders in Europe and the US were conducted; results of these informed the design of focus group guides. Eight focus groups were conducted with European patients, industry representatives and regulators, and with US regulators and European/Canadian health technology assessment (HTA) representatives. Focus groups were analyzed thematically using NVivo. Results: Stakeholder perspectives on how PPS should be designed and conducted were as follows: 1) study design should be informed by the research questions and patient population; 2) preferred treatment attributes and levels, as well as trade-offs among attributes and levels should be investigated; 3) the patient sample and method should match the MPLC phase; 4) different stakeholders should collaborate; and 5) results from PPS should be shared with relevant stakeholders. The value of patient preferences in decision-making was found to increase with the level of patient preference sensitivity of decisions on medical products. Stakeholders mentioned that patient preferences are hardly used in current decision-making. Potential applications for patient preferences across industry, regulatory and HTA processes were identified. Four applications seemed most promising for systematic integration of patient preferences: 1) benefit-risk assessment by industry and regulators at the marketing-authorization phase; 2) assessment of major contribution to patient care by European regulators; 3) cost-effectiveness analysis; and 4) multi criteria decision analysis in HTA. Conclusions: The value of patient preferences for decision-making depends on the level of collaboration across stakeholders; the match between the research question, MPLC phase, sample, and preference method used in PPS; and the sensitivity of the decision regarding a medical product to patient preferences. Promising applications for patient preferences should be further explored with stakeholders to optimize their inclusion in decision-making., (Copyright © 2019 van Overbeeke, Janssens, Whichello, Schölin Bywall, Sharpe, Nikolenko, Phillips, Guiddi, Pravettoni, Vergani, Marton, Cleemput, Simoens, Kübler, Juhaeri, Levitan, de Bekker-Grob, Veldwijk and Huys.)

In India, most women now delivery in hospitals or other facilities, however, maternal and neonatal mortality remains stubbornly high. Studies have shown that mistreatment causes delays in care-seeking, early discharge and poor adherence to post-delivery guidance. This study seeks to understand the variation of women's experiences in different levels of government facilities. This information can help to guide improvement planning. We surveyed 2018 women who gave birth in a representative set of 40 government facilities from across Uttar Pradesh (UP) state in northern India. Women were asked about their experiences of care, using an established scale for person-centred care. We asked questions specific to treatment and clinical care, including whether tests such as blood pressure, contraction timing, newborn heartbeat or vaginal exams were conducted, and whether medical assessments for mothers or newborns were done prior to discharge. Women delivering in hospitals reported less attentive care than women in lower-level facilities, and were less trusting of their providers. After controlling for a range of demographic attributes, we found that better access, higher clinical quality, and lower facility-level, were all significantly predictive of patient-centred care. In UP, lower-level facilities are more accessible, women have greater trust for the providers and women report being better treated than in hospitals. For the vast majority of women who will have a safe and uncomplicated delivery, our findings suggest that the best option would be to invest in improvements mid-level facilities, with access to effective and efficient emergency referral and transportation systems should they be needed., (© The Author(s) 2019. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Background: Recreational noise-induced hearing loss (RNIHL) is a major health issue and presents a huge economic burden on society. Exposure to loud music is not considered hazardous in our society because music is thought to be a source of relaxation and entertainment. However, there is evidence that regardless of the sound source, frequent exposure to loud music, including through personal audio systems (PAS), can lead to hearing loss, tinnitus, difficulty processing speech, and increased susceptibility to age-related hearing loss., Purpose: Several studies have documented temporary threshold shifts (TTS) (a risk indicator of future permanent impairment) in subjects that listen to loud music through their PAS. However, there is not enough information regarding volume settings that may be considered to be safe. As a primary step toward quantifying the risk of RNIHL through PAS, we assessed changes in auditory test measures before and after exposure to music through the popular iPod Touch device set at various volume levels., Research Design: This project design incorporated aspects of both between- and within-subjects and used repeated measures to analyze individual groups., Study Sample: A total of 40 adults, aged 18-31 years with normal hearing were recruited and randomly distributed to four groups. Each group consisted of five males and five females., Data Collection and Analysis: Subjects underwent two rounds of testing (pre- and postmusic exposure), with a 30-min interval, where they listened to a playlist consisting of popular songs through an iPod at 100%, 75%, 50%, or 0% volume (no music). Based on our analysis on the Knowles Electronic Manikin for Acoustic Research, with a standardized 711 coupler, it was determined that listening to the playlist for 30 min through standard earbuds resulted in an average level of 97.0 dBC at 100% volume, 83.3 dBC at 75% volume, and 65.6 dBC at 50% volume. Pure-tone thresholds from 500-8000 Hz, extended high-frequency pure tones between 9-12.5 kHz, and distortion product otoacoustic emissions (DPOAE) were obtained before and after the 30-min music exposure. Analysis of variance (ANOVA) was performed with two between-subjects factors (volume and gender) and one within-subjects factor (frequency). Change (shift) in auditory test measures was used as the outcome for the ANOVA., Results: Results indicated significant worsening of pure-tone thresholds following music exposure only in the group that was exposed to 100% volume at the following frequencies: 2, 3, 4, 6 and 8 kHz. DPOAEs showed significant decrease at 2000 and 2822 Hz, also only for the 100% volume condition. No significant changes were found between pre- and postmusic exposure measures in groups exposed to 75%, 50%, or 0% volume conditions. Follow-up evaluations conducted a week later indicated that pure-tone thresholds had returned to the premusic exposure levels., Conclusions: These results provide quantifiable information regarding safe volume control settings on the iPod Touch with standard earbuds. Listening to music using the iPod Touch at 100% volume setting for as little as 30 min leads to TTS and worsening of otoacoustic emissions, a risk for permanent auditory damage., (American Academy of Audiology.)

Background : Globally, opportunities to validate government reports through external audits are rare, notably in India. A cross-sectional maternal health study in Uttar Pradesh, India's most populous state, compares government administrative data and externally collected data on maternal health service indicators. Objectives : Our study aims to determine the level of concordance between government-reported health facility data compared to externally collected health facility data on the same maternal healthcare quality indicators. Second, our study aims to explore whether the level of agreement between government administrative data versus the externally collected data differs by level of facility or by type of maternal health service. Methods : Facility assessment surveys were administered to key health staff by government-hired enumerators from January 2017 to March 2017 at nearly 750 government health facilities across UP. The same survey was re-conducted by external data collectors from August 2017 to October 2017 at 40 of the same facilities. We conduct comparative analyses of the two datasets for agreement among the same measures of maternal healthcare quality. Results : The findings indicate concordance between most indicators across government administrative data and externally collected health facility data. However, when stratified by facility-level or service type, results suggest significant over-reporting in the government administrative data on indicators that are incentivized. This finding is consistent across all levels of facilities; however, the most significant disparities appear at higher-level facilities, namely District Hospitals. Conclusion : This study has a number of important programmatic and policy implications. Government administrative health data have the potential to be highly critical in informing large-scale quality improvements in maternal healthcare quality, but its credibility must be readily verifiable and accessible to politicians, researchers, funders, and most importantly, the public, to improve the overall health, patient experience, and well-being of women and newborns.

Background: Standard of care treatment for multicentric lymphoma in dogs remains doxorubicin (DOX)-based combination chemotherapy, but owners may hesitate to commit the time and financial resources to complete such a protocol, typically requiring 12-16 visits. Rabacfosadine (RAB), a double prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl) guanine, has substantial single-agent activity in dogs with lymphoma, and a different mechanism of action than DOX., Hypothesis/objectives: Our objective was to evaluate the efficacy and adverse effect (AE) profile of alternating doses of RAB and DOX in dogs with naïve multicentric lymphoma., Animals: Fifty-four dogs with previously untreated lymphoma., Methods: Open-label, multicenter prospective clinical trial. Dogs received alternating RAB (1.0 mg/kg IV weeks 0, 6, 12) and DOX (30 mg/m 2 IV weeks 3, 9, 15). Dogs that achieved complete response (CR) were followed by monthly evaluations. Complete clinicopathological evaluation and assessment of remission and AEs were performed every 21 days., Results: The overall response rate was 84% (68%; CR; 16%; partial response [PR)]. The overall median progression-free interval (PFI) was 194 days (216 for CR and 63 for PR). Most AEs were mild and self-limiting: gastrointestinal and hematologic AEs were most common. Thirteen dogs experienced dermatologic AEs, and 2 dogs developed grade 5 pulmonary fibrosis., Conclusions and Clinical Importance: Alternating RAB/DOX generally was well tolerated and resulted in PFIs comparable to standard DOX-based multi-agent protocols, with fewer treatment visits. Most adverse events were mild or moderate and self-limiting. Further studies are warranted to explore long-term outcome and other RAB chemotherapy combinations., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Obstetric fistula, a preventable maternal morbidity characterised by chronic bladder and/or bowel incontinence, is widespread in Nigeria. This qualitative, multi-site study examined the competing narratives on obstetric fistula causality in Nigeria. Research methods were participant observation and in-depth interviews with 86 fistula patients and 43 healthcare professionals. The study found that both patient and professional narratives identified limited access to medical facilities as a major factor leading to obstetric fistula. Patients and professionals beliefs regarding the access problem, however, differed significantly. The majority of fistula patients reported either delivering or attempting to deliver in medical facilities and most patients attributed fistula to a lack of trained medical staff and mismanagement at medical facilities. Conversely, a majority of health professionals believed that women developed obstetric fistula because they chose to deliver at home due to women's traditional beliefs about womanhood and childbirth. Both groups described financial constraints and inadequate transport to medical facilities during complicated labour as related to obstetric fistula onset. Programmatic insights derived from these findings should inform fistula prevention interventions both with healthcare professionals and with Nigerian women.

We report size-based sorting of micro- and sub-micron particles using optical forces on a planar optofluidic chip. Two different combinations of fluid flow and optical beam directions in liquid-core waveguides are demonstrated. These methods allow for tunability of size selection and sorting with efficiencies as high as 100%. Very good agreement between experimental results and calculated particle trajectories in the presence of flow and optical forces is found.

We present the first integration of fluidically tunable filters with a separate particle detection channel on a single planar, optofluidic chip. Two optically connected, but fluidically isolated liquid-core antiresonant reflecting optical waveguide (ARROW) segments serve as analyte and spectral filter sections, respectively. Ultrasensitive detection of fluorescent nanobeads with high signal-to-noise ratio provided by a fluidically tuned excitation notch filter is demonstrated. In addition, reconfigurable filter response is demonstrated using both core index tuning and bulk liquid tuning. Notch filters with 43 dB rejection ratio and a record 90 nm tuning range are implemented by using different mixtures of ethylene glycol and water in the filter section. Moreover, absorber dyes and liquids with pH-dependent transmission in the filter channel provide additional spectral control independent of the waveguide response. Using both core index and pH control, independent filter tuning at multiple wavelengths is demonstrated for the first time. This extensive on-chip control over spectral filtering as one of the fundamental components of optical particle detection techniques offers significant advantages in terms of compactness, cost, and simplicity, and opens new opportunities for waveguide-based optofluidic analysis systems.

The use of scattered light images is shown to be an attractive method for the characterization of optofluidic waveguides. The method is shown to be capable of measuring waveguide propagation losses and transmissions between solid and liquid-core structures. Measurement uncertainties are considered and characterized and were typically less than 15%.

Spectral filtering is an essential component of biophotonic methods such as fluorescence and Raman spectroscopy. Predominantly utilized in bulk microscopy, filters require efficient and selective transmission or removal of signals at one or more wavelength bands. However, towards highly sensitive and fully self-contained lab-on-chip systems, the integration of spectral filters is an essential step. In this work, a novel optofluidic solution is presented in which a liquid-core optical waveguide both transports sample analytes and acts as an efficient filter for advanced spectroscopy. To this end, the wavelength dependent nature of interference-based antiresonant reflecting optical waveguide technology is exploited. An extinction of 37 dB, a narrow rejection band of only 2.5 nm and a free spectral range of 76 nm using three specifically designed dielectric layers are demonstrated. These parameters result in an 18.4-fold increase in the signal-to-noise ratio for on-chip fluorescence detection. In addition, liquid-core waveguide filters with three operating wavelengths were designed for Förster resonance energy transfer detection and demonstrated using doubly labeled oligonucleotides. Incorporation of high-performance spectral processing illustrates the power of the optofluidic concept where fluidic channels also perform optical functions to create innovative and highly integrated lab-on-chip devices.

Objective: To evaluate factors associated with second remission in dogs with lymphoma retreated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) protocol after relapse following initial treatment with a first-line 6-month CHOP protocol., Design: Retrospective case series., Animals: 95 dogs with lymphoma., Procedures: Medical records were reviewed. Remission duration was estimated by use of the Kaplan-Meier method. Factors potentially associated with prognosis were examined., Results: Median remission duration after the first-line CHOP protocol was 289 days (range, 150 to 1,457 days). Overall, 78% (95% confidence interval [CI], 69% to 86%) of dogs achieved a complete remission following retreatment, with a median second remission duration of 159 days (95% CI, 126 to 212 days). Duration of time off chemotherapy was associated with likelihood of response to retreatment; median time off chemotherapy was 140 days for dogs that achieved a complete remission after retreatment and 84 days for dogs that failed to respond to retreatment. Second remission duration was associated with remission duration after initial chemotherapy; median second remission duration for dogs with initial remission duration ≥ 289 days was 214 days (95% CI, 168 to 491 days), compared with 98 days (95% CI, 70 to 144 days) for dogs with initial remission duration < 289 days., Conclusions and Clinical Relevance: Findings suggested that retreatment with the CHOP protocol can be effective in dogs with lymphoma that successfully complete an initial 6-month CHOP protocol.

Optofluidic platforms used for biomolecular detection require spectral filtering for distinguishing analyte signals from unwanted background. Towards a fully integrated platform, an on-chip filter is required. Selective deposition of dielectric thin films on an optofluidic sensor based on antiresonant reflecting optical waveguide (ARROW) technology provides the means for localized, on-chip optical filtering. We present a lift-off technique, compatible with thin-film processing including plasma-enhanced chemical vapor and sputtering deposition. The resulting optofluidic notch filters exhibited a 20 dB rejection with linewidths as low as 20 nm for approximately 1 cm long chips consisting of liquid-core and solid-core waveguides.

The development of on-chip methods to manipulate particles is receiving rapidly increasing attention. All-optical traps offer numerous advantages, but are plagued by large required power levels on the order of hundreds of milliwatts and the inability to act exclusively on individual particles. Here, we demonstrate a fully integrated electro-optical trap for single particles with optical excitation power levels that are five orders of magnitude lower than in conventional optical force traps. The trap is based on spatio-temporal light modulation that is implemented using networks of antiresonant reflecting optical waveguides. We demonstrate the combination of on-chip trapping and fluorescence detection of single microorganisms by studying the photobleaching dynamics of stained DNA in E. coli bacteria. The favorable size scaling facilitates the trapping of single nanoparticles on integrated optofluidic chips.

A new waveguide design for an optofluidic chip is presented. It mitigates multi-mode behavior in solid and liquid-core waveguides by increasing fundamental mode coupling to 82% and 95%, respectively. Additionally, we demonstrate a six-fold improvement in lateral confinement of optically guided dielectric microparticles and double the detection efficiency of fluorescent particles.

Optical traps have become widespread tools for studying biological objects on the micro and nanoscale. However, conventional laser tweezers and traps rely on bulk optics and are not compatible with current trends in optofluidic miniaturization. Here, we report a new type of particle trap that relies on propagation loss in confined modes in liquid-core optical waveguides to trap particles. Using silica beads and E. coli bacteria, we demonstrate unique key capabilities of this trap. These include single particle trapping with micron-scale accuracy at arbitrary positions over waveguide lengths of several millimeters, definition of multiple independent particle traps in a single waveguide, and combination of optical trapping with single particle fluorescence analysis. The exclusive use of a two-dimensional network of planar waveguides strongly reduces experimental complexity and defines a new paradigm for on-chip particle control and analysis.

Ultrahigh sensitivity detection of particles in solution implies the ability to detect at very low concentrations. At the single-particle level, this is achieved through fluorescence detection, reaching down to single fluorophores. Sensitivity may also be improved by concentrating many particles into a compact cluster, thus "integrating" the signal of many particles. We show how both ways can be combined on an optofluidic chip in a fully planar geometry utilizing counterpropagating liquid-core waveguide modes to form a loss-based optical trap. This all-optical concentrator can increase the concentration of particles by more than 2 orders of magnitude and also provides a convenient, nondispersive means of transport for particle ensembles.

Optical sensing platforms based on anti-resonant reflecting optical waveguides (ARROWs) with hollow cores have been used for bioanalysis and atomic spectroscopy. These integrated platforms require that hollow waveguides interface with standard solid waveguides on the substrate to couple light into and out of test media. Previous designs required light at these interfaces to pass through the anti-resonant layers.We present a new ARROW design which coats the top and sides of the hollow core with only SiO2, allowing for high interface transmission between solid and hollow waveguides. The improvement in interface transmission with this design is demonstrated experimentally and increases from 35% to 79%. Given these parameters, higher optical throughputs are possible using single SiO2 coatings when hollow waveguides are shorter than 5.8 mm., ((c) 2008 Optical Society of America)

We introduce a method for optical characterization of hollow-core optical waveguides. Radiation pressure exerted by the waveguide modes on dielectric microspheres is used to analyze salient properties such as propagation loss and waveguide mode profiles. These quantities were measured for quasi-single-mode and multimode propagation in on-chip liquid-filled hollow-core antiresonant reflecting optical waveguides. Excellent agreement with analytical and numerical models is found, demonstrating that optically induced particle transport provides a simple, inexpensive, and nondestructive alternative to other characterization methods.

Submonolayer coatings of noble-metal nanoparticle liquids (NPLs) are shown to provide replenishable surfaces with robust asperities and metallic conductivity that extends the durability of electrical relays by 10 to 100 times (depending on the current driven through the contact) as compared to alternative approaches. NPLs are single-component materials consisting of a metal nanoparticle core (5-20 nm Au or Pt nanoparticles) surrounded by a covalently tethered ionic-liquid corona of 1.5 to 2 nm. Common relay failure modes, such as stiction, surface distortion, and contact shorting, are suppressed with the addition of a submonolayer of NPLs to the contact surfaces. This distribution of NPLs results in a force profile for a contact-retraction cycle that is distinct from bare Au contacts and thicker, multilayer coatings of NPLs. Postmortem examination reveals a substantial decrease in topological change of the electrode surface relative to bare contacts, as well as an indication of lateral migration of the nanoparticles from the periphery towards the contact. A general extension of this concept to dynamic physical interfaces experiencing impact, sliding, or rolling affords alternatives to increase reliability and reduced losses for transmittance of electrical and mechanical energy.

Objective: To evaluate factors associated with survival in dogs with nasal carcinomas that did not receive treatment or received only palliative treatment., Design: Retrospective case series., Animals: 139 dogs with histologically confirmed nasal carcinomas., Procedures: Medical records, computed tomography images, and biopsy specimens of nasal carcinomas were reviewed. Only dogs that were not treated with radiation, surgery, chemotherapy, or immunotherapy and that survived > or = 7 days from the date of diagnosis were included. The Kaplan-Meier method was used to estimate survival time. Factors potentially associated with survival were compared by use of log-rank and Wilcoxon rank sum tests. Multivariable survival analysis was performed by use of the Cox proportional hazards regression model., Results: Overall median survival time was 95 days (95% confidence interval [CI], 73 to 113 days; range, 7 to 1,114 days). In dogs with epistaxis, the hazard of dying was 2.3 times that of dogs that did not have epistaxis. Median survival time of 107 dogs with epistaxis was 88 days (95% CI, 65 to 106 days) and that of 32 dogs without epistaxis was 224 days (95% CI, 54 to 467 days)., Conclusions and Clinical Relevance: The prognosis of dogs with untreated nasal carcinomas is poor. Treatment strategies to improve outcome should be pursued.

Phosphazene rings with (dimethylamino)ethoxy (1, 2), pyridylmethoxy (3), or (dimethylamino)propoxy (4) chains were synthesized and quaternized at the substitutent nitrogen by treatment with methyl iodide at 35 degrees C over 3-6 h to give polyiodo salts, 5-8. Subsequent metathesis with LiN(SO(2)CF(3))(2) or NaBF(4) gave the respective ionic salts, 9-13. The amide salts, 9-12, were viscous liquids with pour points at 55-100 degrees C, and the tetrafluoroborate salt, 13, was a solid, mp 168 degrees C. The compositions of 2 and 5-13 were confirmed by elemental analysis and spectroscopic methods. Compounds 1, 2, and 4 were viscous liquids (d(25) = 1.67 g cm(-3); eta(25) = 0.76-1.56 mPa s(-1) ) with pour points at approximately 15 degrees C. The solid polyquaternary salts, 5-8, melted at 130-194 degrees C. The ionic liquids, 9-12, had an average density of approximately 1.73 g cm(-3) at 25 degrees C, and viscosities (25 degrees C) ranged between 68.3 and 139.2 mPa s(-1). A plot of the viscosities of 9-12 vs temperature revealed an almost linear correlation between 55 and 120 degrees C. Friction and wear properties of water with 0.25 wt % of 9-12 as boundary lubricant additives were evaluated on Si(3)N(4)/Si(3)N(4) ceramic interfaces. The most significant observation is that they caused a decrease in the running-in period.

Over four-hundred crude extracts from 202 plant species distributed among 131 plant families were evaluated for their bioactivity against brine shrimp (Artemia salina). Activity was determined for both the organic (CH2Cl2:MeOH) and aqueous extracts against A. salina in a 96 well-plate assay. Of the greater than four-hundred extracts tested, 21 organic and 6 aqueous extracts demonstrated potent cytotoxic activity (LC50 = < 100 microg/ml). Three of these organic extracts (Crateva religiosa, Diospyros dichrophylla, and Olax subscorpioidea) were chosen for chemical investigations due to their high activity and a lack of prior investigations. Chemical analysis of these extracts resulted in the isolation of oleanolic acid (1) and 4-epi-hederagenin (2) from C. religiosa, isodiospyrin (3) from D. dichrophylla, and santalbic acid (4) from O. subscorpioidea.

The purpose of this randomized, multicenter study was to evaluate the toxicity and efficacy of liposome-encapsulated doxorubicin (LED) and doxorubicin (DOX) in the treatment of feline vaccine-associated sarcoma (VAS). Cats were divided according to their disease status into a microscopic arm (no evidence of gross disease) and a macroscopic arm (evidence of gross disease). Each arm was randomized to receive either LED (1-1.5 mg/kg i.v. q3 weeks) or DOX (1 mg/kg i.v. q3 weeks). Thirty-three cats were entered in the macroscopic arm of the study with an overall response rate of 39% (5 complete response and 8 partial response) and a median time to progression of 84 days. Response rates were not different between LED and DOX. Seventy-five cats were entered into the microscopic arm. When compared to a similar historical control population treated with surgery alone, the cats receiving chemotherapy had a prolonged median disease-free interval (388 days versus 93 days). No difference in efficacy was detected between LED and DOX. LED at 1.5 mg/kg induced delayed nephrotoxicosis in 23%, necessitating a decrease in the recommended dosage to 1 mg/kg, and cutaneous toxicosis in 21.7% of treated cats. This study showed that both DOX and LED are efficacious in the treatment of VAS and should be considered in the treatment of this tumor.

Purpose: To evaluate the short-term adverse effects of administration of dolastatin-10 (Dol-10) to dogs with spontaneously occurring malignant tumors., Methods: A total of 34 tumor-bearing dogs were given Dol-10 as a rapid intravenous bolus every 14 days at starting dosages ranging from 200 to 350 microg/m(2). Acute and short-term adverse effects, antitumor response, and duration of response were characterized., Results: The maximum tolerated dose varied greatly from patient to patient, but a reasonable starting dose for further studies was established at 300 microg/m(2). The median number of treatments per dog was 2 (range 1 to 17). Granulocytopenia was the dose-limiting toxicity. The overall response rate was 3%, consisting of a complete and durable (30 months) response in a dog with high-grade malignant lymphoma that was refractory to standard therapy. Two minor or transient responses were observed, and two dogs experienced disease stabilization for 8 and 16 weeks., Conclusions: Dol-10 appears to be well tolerated in tumor-bearing dogs at doses approaching those tolerated by humans. The clinical activity observed in dogs with non-Hodgkin's lymphoma warrants further investigation.

Biomedical studies with animal models have demonstrated that cis-9, trans-11 conjugated linoleic acid (CLA), the predominant isomer found in milk fat from dairy cows, has anticarcinogenic effects. We recently demonstrated endogenous synthesis of cis-9, trans-11 CLA from ruminally derived trans-11 C18:1 by Delta(9)-desaturase in lactating dairy cows. The present study further examined endogenous synthesis of cis-9, trans-11 CLA and quantified its importance by increasing substrate supply using partially hydrogenated vegetable oil (PHVO) as a source of trans-11 C18:1 and blocking endogenous synthesis using sterculic oil (SO) as a source of cyclopropene fatty acids which specifically inhibit Delta(9)-desaturase. Four cows were abomasally infused with 1) control, 2) PHVO, 3) SO, and 4) PHVO+SO in a 4 x 4 Latin square design. With infusion of PHVO, cis-9, trans-11 CLA was increased by 17% in milk fat. Consistent with inhibition of desaturase, SO treatments increased milk fat ratios for the fatty acid pairs effected by Delta(9)-desaturase, C14:0/cis-9 C14:1, C16:0/cis-9 C16:1, and C18:0/cis-9 C18:1. The role of endogenous synthesis of CLA was evident from the 60-65% reduction in cis-9, trans-11 CLA which occurred in milk fat with SO treatments. cis-9 C14:1 originates from desaturation of C14:0 by Delta(9)-desaturase and can be used to estimate the extent of SO inhibition of Delta(9)-desaturase. When this correction factor was applied, endogenous synthesis was estimated to account for 78% of the total cis-9, trans-11 CLA in milk fat. Thus, endogenous synthesis was the major source of cis-9, trans-11 CLA in milk fat of lactating cows.

Proliferative and apoptotic fractions of tumors were evaluated in 41 dogs with lymphoma for prediction of response to chemotherapy. All dogs had advanced clinical stage tumors, were untreated prior to study, and received identical induction-remission chemotherapy. Tumor cell proliferation was determined in all pretreatment biopsy specimens and in 18 specimens collected at the time of clinical relapse from remission. Quantitative measures included mitotic index and immunoreactivities for proliferating cell nuclear antigen (PCNA) and Ki-67. Apoptotic index was evaluated from 40 dogs pretreatment and from 16 dogs at the time of first relapse. Pretreatment tumor values for Ki-67, PCNA, and apoptosis were compared with posttreatment values. The median first relapse-free interval (RFI) and overall survival (OS) time were 174 days and 445 days, respectively. Of the proliferation markers, only the results of the Ki-67 analysis were predictive for duration of the first RFI but not OS. Pretreatment apoptotic index was also predictive of the duration of first RFI but not OS. No significant predictive value for comparison of the pretreatment and postrelapse values was demonstrated. Ki-67 labeling index and apoptotic indexes were combined to form both a proliferation/apoptotic ratio (PAR) and a sum, or turnover index. Only the PAR was predictive for duration of first RFI on multivariate analysis. Other variables that were evaluated for their influence on treatment outcome included patient age, weight, gender, clinical stage, clinical substage, and tumor immunophenotype. Of these variables, only immunophenotype was found to be of value for predicting duration of first RFI and OS.