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A systematic review with meta-analysis was conducted to establish the impact of menopause health education on quality of life (QoL) among menopausal women. Research suggests that specific educational programs can support and enable women during the physical and emotional transition through menopause. The CINAHL, Medline, APA, Embase and Google Scholar databases were searched between 30 November 2021 and 9 January 2022 using the PRISMA guidelines. The Cochrane risk of bias tool was used to critically evaluate the included studies. Review Manager software was used to conduct the meta-analysis of suitable studies. Eight papers were eligible for this review. The participants were aged between 40 and 60 years, with diagnosis of menopause stemming from changes in the menstrual cycle to a last menstrual period of 7 years. Follow-up data were collected between 1 and 4 months post education. Meta-analysis of both the primary outcome (QoL) and secondary outcome (symptom control) demonstrated statistically significant improvements post intervention. Papers not suitable for meta-analysis were reviewed narratively; two papers assessing the primary outcome (QoL) demonstrated an improvement, but only one to a statistically significant level. Secondary outcomes revealed improvements, with all bar one paper doing so to statistical significance. Menopause health education demonstrated an improvement in both QoL and symptom control in menopausal women; however, given some weaknesses in the included studies, further research is justified. Limitations include participants' level of education, geographical location, risk of bias, that only half of the papers addressed participant use of hormone replacement therapy and length of follow-up.
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Menopausia , Calidad de Vida , Humanos , Femenino , Adulto , Persona de Mediana Edad , Menopausia/psicología , Terapia de Reemplazo de HormonasRESUMEN
The objective of this study was to investigate the effect of increasing stocking rate (SR) and extending grazing season (GS) length on pasture and animal productivity on a marginal, poorly draining soil type. The study was a multiyear (2017 to 2020, inclusive) whole farm systems evaluation with a 2 × 2 factorial experimental arrangement of treatments. The systems evaluated comprised 2 GS lengths, average (AGS; 205 d) and extended (EGS; 270 d), and the 2 whole farm stocking rates were medium (2.5 cows/ha) and high (2.9 cows/ha). We used this study design to create 4 grazing system intensities (500, 600, 700, and 800 cow grazing days per hectare per year). In 2017, cows were randomly allocated to 1 of the 4 whole farm systems precalving and remained on the same treatments for the duration of the study. We found no significant differences in total average annual pasture production [14,133 ± 538 kg of dry matter (DM) per hectare] or sward chemical composition between GS and SR treatments over the 4-yr period, with the exception of average crude protein content, which was lower for EGS (211 g/kg DM) compared with AGS (218 g/kg DM). Grazed pasture production was significantly increased in EGS treatments (+758 kg of DM/ha) compared with AGS (9,917 kg of DM/ha), whereas conserved silage DM production was greater for AGS (+716 kg of DM/ha) compared with EGS (3,583 kg of DM/ha). Neither GS nor SR had a significant effect on daily or cumulative lactation milk and fat plus protein production per cow (5,039 and ±440 kg, respectively). Increasing SR resulted in increased milk fat plus protein yield per hectare based on increased grazed pasture utilization. These results add further credence to the important additive contributions of both extended grazing and SR intensification to achieve high levels of grazed pasture utilization and milk production per hectare while reducing supplementary feed requirements within spring-calving grazing systems.
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Alimentación Animal , Leche , Femenino , Bovinos , Animales , Leche/metabolismo , Estaciones del Año , Industria Lechera/métodos , Lactancia , Proteínas de la Leche/metabolismo , Dieta/veterinariaRESUMEN
Pressure ulcers (PUs) remain a chronic health problem with severe impacts on healthcare systems. Early detection is crucial to providing effective interventions. However, detecting PUs currently relies on subjective tissue evaluations, such as visual skin assessment, precluding interventions prior to the development of visible tissue damage. There is an unmet need for solutions that can detect early tissue damage before visual and tactile signs occur. Assessments based on sub-epidermal moisture (SEM) measurements represent an opportunity for robust and objective early detection of PUs, preventing broken skin PUs in more high-risk patients at high-risk anatomical locations. While SEM assessment technology has been validated in computational, bench and tissue phantom models, validation in soft tissue was absent. In this study, we successfully validated the ability of a commercially available SEM assessment device to measure and detect sub-epidermal moisture changes in a novel ex vivo porcine soft tissue model of localised oedema. When controlled and incremental fluid volumes (Phosphate Buffer Solution) were injected into porcine soft tissues, statistically significant differences were found in SEM values between fluid-injected sites, representing an inflammatory oedematous condition, and healthy tissue control sites, as measured by the SEM device. The device provided reproducible readings by detecting localised oedema changes in soft tissues, reflecting the build-up of fluid as small as 1 ml into the underlying tissue. Spatial characterization experiments described the ability of the device technology to differentiate between healthy and oedematous tissue. Our findings validate the use of SEM assessment technology to measure and quantify localized oedema.
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Úlcera por Presión , Humanos , Porcinos , Animales , Úlcera por Presión/diagnóstico , Úlcera por Presión/prevención & control , Epidermis , Piel , Edema/diagnóstico , SupuraciónRESUMEN
BACKGROUND: To improve the effectiveness of interventions targeting non-adherence in older adults, a systematic approach to intervention design is required. The content of complex interventions and design decisions are often poorly described in published reports which makes it difficult to explore why they are ineffective. This intervention development study reports on the design of a community pharmacy-based adherence intervention using 11 Behaviour Change Techniques (BCTs) which were identified from previous qualitative research with older patients using the Theoretical Domains Framework. METHODS: Using a group consensus approach, a five-step design process was employed. This focused on decisions regarding: (1) the overall delivery format, (2) formats for delivering each BCT; (3) methods for tailoring BCTs to individual patients; (4) intervention structure; and (5) materials to support intervention delivery. The APEASE (Affordability; Practicability; Effectiveness/cost-effectiveness; Acceptability; Side effects/safety; Equity) criteria guided the selection of BCT delivery formats. RESULTS: Formats for delivering the 11 BCTs were agreed upon, for example, a paper medicines diary was selected to deliver the BCT 'Self-monitoring of behaviour'. To help tailor the intervention, BCTs were categorised into 'Core' and 'Optional' BCTs. For example, 'Feedback on behaviour' and 'Action planning' were selected as 'Core' BCTs (delivered to all patients), whereas 'Prompts and cues' and 'Health consequences' were selected as 'Optional' BCTs. A paper-based adherence assessment tool was designed to guide intervention tailoring by mapping from identified adherence problems to BCTs. The intervention was designed for delivery over three appointments in the pharmacy including an adherence assessment at Appointment 1 and BCT delivery at Appointments 2 and 3. CONCLUSIONS: This paper details key decision-making processes involved in moving from a list of BCTs through to a complex intervention package which aims to improve older patients' medication adherence. A novel approach to tailoring the content of a complex adherence intervention using 'Core' and 'Optional' BCT categories is also presented. The intervention is now ready for testing in a feasibility study with community pharmacists and patients to refine the content. It is hoped that this detailed report of the intervention content/design process will allow others to better interpret the future findings of this work.
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Terapia Conductista/métodos , Cumplimiento de la Medicación/psicología , Farmacias/organización & administración , Teoría Psicológica , Anciano , HumanosRESUMEN
BACKGROUND: The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) is a national precision medicine study incorporating centralized genomic testing to direct refractory cancer patients to molecularly targeted treatment subprotocols. This treatment subprotocol was designed to screen for potential signals of efficacy of ado-trastuzumab emtansine (T-DM1) in HER2-amplified histologies other than breast and gastroesophageal tumors. METHODS: Eligible patients had HER2 amplification at a copy number (CN) >7 based on targeted next-generation sequencing (NGS) with a custom Oncomine AmpliSeq™ (ThermoFisher Scientific) panel. Patients with prior trastuzumab, pertuzumab or T-DM1 treatment were excluded. Patients received T-DM1 at 3.6 mg/kg i.v. every 3 weeks until toxicity or disease progression. Tumor assessments occurred every three cycles. The primary end point was centrally assessed objective response rate (ORR). Exploratory end points included correlating response with HER2 CN by NGS. The impact of co-occurring genomic alterations and PTEN loss by immunohistochemistry were also assessed. RESULTS: Thirty-eight patients were enrolled and 36 included in efficacy analysis. Median prior therapies in the metastatic setting was 3 (range 0-9; unknown in one patient). Median HER2 CN was 17 (range 7-139). Partial responses were observed in two (5.6%) patients: one mucoepidermoid carcinoma of parotid gland and one parotid gland squamous cell cancer. Seventeen patients (47%) had stable disease including 8/10 (80%) with ovarian and uterine carcinomas, with median duration of 4.6 months. The 6-month progression-free survival rate was 23.6% [90% confidence interval 14.2% to 39.2%]. Common toxicities included fatigue, anemia, fever and thrombocytopenia with no new safety signals. There was a trend for tumor shrinkage with higher levels of gene CN as determined by the NGS assay. CONCLUSION: T-DM1 was well tolerated. While this subprotocol did not meet the primary end point for ORR in this heavily pre-treated diverse patient population, clinical activity was seen in salivary gland tumors warranting further study in this tumor type in dedicated trials.
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Ado-Trastuzumab Emtansina/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor/genética , Neoplasias/tratamiento farmacológico , Receptor ErbB-2/genética , Ado-Trastuzumab Emtansina/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/farmacología , Resistencia a Antineoplásicos/genética , Femenino , Amplificación de Genes , Humanos , Persona de Mediana Edad , National Cancer Institute (U.S.) , Neoplasias/genética , Neoplasias/mortalidad , Neoplasias/patología , Medicina de Precisión/métodos , Supervivencia sin Progresión , Receptor ErbB-2/antagonistas & inhibidores , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: Our aims were to: establish the clinical significance of ultrasound, thermography, photography and subepidermal moisture (SEM) measurement; determine the accuracy of ultrasound, thermography, photography and SEM measurement in detecting skin/tissue damage; determine the relative accuracy of one of these assessment methods over another; make recommendations for practice pertaining to assessment of early skin/tissue damage. METHOD: The following databases, Cochrane Wounds Group Specialised Register, The Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Ovid EMBASE, Elsevier version, EBSCO CINAHL, ClinicalTrials.gov , WHO International Clinical Trials Registry (ICTR) and The EU Clinical Trials Register were searched for terms including; thermography, ultrasound, subepidermal moisture, photograph and pressure ulcer. RESULTS: We identified four SEM, one thermography and five ultrasound studies for inclusion in this review. Data analysis indicated that photography was not a method which allowed for the early prediction of PU presence. SEM values increased with increasing tissue damage, with the sacrum and the heels being the most common anatomical locations for the development of erythema and stage I PUs. Thermography identified temperature changes in tissues and skin that may give an indication of early PU development; however the data were not sufficiently robust. Ultrasound detected pockets of fluid/oedema at different levels of the skin that were comparable with tissue damage. Thus, SEM and ultrasound were the best methods for allowing a more accurate assessment of early skin/tissue damage. Using the EBL Critical Appraisal Tool the overall validities of the studies varied between 33.3-55.6%, meaning that there is potential for bias within all the included studies. All of the studies were situated at level IV, V and VII of the evidence pyramid. Although the methodological quality of the studies warrants consideration, these studies showed the potential that SEM and ultrasound have in early PU detection. CONCLUSION: SEM and ultrasound are promising in the detection and prediction of early tissue damage and PU presence. However, these methods should be further studied to clarify their potential for use more widely in PU prevention strategies.
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Úlcera por Presión/diagnóstico por imagen , Piel/diagnóstico por imagen , Termografía , Ultrasonografía , Diagnóstico Precoz , Eritema , HumanosRESUMEN
OBJECTIVE: There is a rising incidence of diabetes worldwide; however there seems to be a higher incidence and prevalence rates in the Arab world when compared with the global average. 1 Out of the top 10 countries with the highest prevalence rates, six are Arab countries and almost 20.5 million people in that part of the world live with diabetes. Despite this, published scientific research from the 22 Arab countries is limited and seems to be of lower quality when compared with the rest of the developed world. 2 Therefore, our aim was to explore the contribution of the different Arab countries in the world literature, to identify the diabetic foot ulcer (DFU) prevalence and incidence rates and to quality appraise these studies. METHOD: A systematic review, following PRISMA guidelines, was undertaken to identify the incidence and prevalence of DFUs in the Arab world. The following databases were searched: PubMed, Embase CINAHL, Web of Science (Scopus), Global Health and EBSCO Results: A total of nine papers were identified. The mean prevalence of DFU in Saudi Arabia was 11.85% (4.7-19%), in Egypt was 4.2% (1-7.4%), in Jordan was 4.65% (4-5.3%), in Bahrain was 5.9% and in Iraq was 2.7%. A single study identified DFU incidence in Saudi Arabia as 1.8% between 2009-2010. CONCLUSION: The mean prevalence rates of DFU were highest in Saudi Arabia and Bahrain and lowest in Iraq. Saudi Arabia had the only reported incidence study, thus findings could not be compared to other countries of the Arab world. There were no studies identified during our search reporting prevalence rates of DFU in 17 of the 22 Arab countries. It is clear that further research is required to determine the incidence and prevalance of DFUs in the Arab world and that progress is needed in order to improve the quality of research conducted in those countries.
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Pie Diabético/epidemiología , Bahrein/epidemiología , Egipto/epidemiología , Humanos , Incidencia , Irak/epidemiología , Jordania/epidemiología , Prevalencia , Arabia Saudita/epidemiologíaRESUMEN
OBJECTIVE: Diabetic foot ulcers (DFUs) are a significant challenge in wound care practice. Our aim was to evaluate the combined use of of two therapies, ultrasound and electrostimulation, in the treatment of DFUs. METHOD: This study employed a prospective, non-comparative, case series design, undertaken in a podiatry-led diabetic foot clinic, in an acute hospital setting, in an urban location in Ireland. We recruited patinets with hard-to-heal DFUs who were treated twice a week with combined modulated ultrasound and electric current stimulation. RESULTS: We recruited seven patients with eight chronic DFUs. A mean wound size reduction of 71% was achieved and there were no adverse reactions to the therapy. CONCLUSION: The results of this small case series indicate that combined modulated ultrasound and electric current stimulation offers promise as an adjunct therapy for DFUs. Further large scale trials are now warranted.
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Pie Diabético/terapia , Terapia por Estimulación Eléctrica , Úlcera por Presión/terapia , Terapia por Ultrasonido , Úlcera Varicosa/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Cicatrización de HeridasRESUMEN
The productivity of grazing systems is primarily limited by the scale and efficiency of systems applied to the grazable land platform adjacent to the milking parlor. The objective of this study was to compare forage production, utilization and quality, milk production, and requirement for supplementary feeds for 2 different grazing platform stocking rate (GPSR) treatments over 4 yr. Animals were randomly allocated to 1 of 2 GPSR treatments: high-closed (HC; 3.1 cows/ha) and high-open (HO; 4.5 cows/ha), which were designed to represent alternative GPSR in a post-European Union milk quota, spring calving, pasture-based milk production system. Animal production data were analyzed using Proc MIXED of SAS with GPSR, year, and parity included as fixed effects in the final model. Within a seasonal spring calving grazing system, at high GPSR and offering moderate amounts of additional supplements based on pasture supply deficits, both systems produced more milk and fat plus protein per hectare in comparison with Irish commercial dairy farms. Although requiring additional supplementation, increased GPSR resulted in increased milk production per hectare but also in an increased requirement for concentrate and forage supplementation during lactation. No significant influence of GPSR was found on body weight and body condition score or reproductive performance during the 4-yr study period. In addition, GPSR also had no effect on pasture production, utilization, or quality during the study period. The strategic use of additional supplements with restricted pasture availability at higher GPSR maintained milk production per cow and significantly increased milk production per hectare.
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Alimentación Animal/análisis , Industria Lechera/métodos , Industria Lechera/normas , Métodos de Alimentación/veterinaria , Lactancia/fisiología , Animales , Bovinos , Suplementos Dietéticos , Métodos de Alimentación/normas , Femenino , Leche/metabolismo , Embarazo , Distribución Aleatoria , Estaciones del AñoRESUMEN
BACKGROUND: Use of a levonorgestrel-releasing intrauterine system (LNG-IUS) in humans may alter vaginal microbial populations and susceptibility to pathogens. This study evaluated the time-dependent effects of an LNG-IUS on the vaginal microbiome of the baboon, a useful animal model for reproductive studies. METHODS: Levonorgestrel-releasing intrauterine systems were inserted into three reproductively mature, female baboons. The animals were evaluated for 6 months by physical examination and Gram-stained cytology. The vaginal microbiota was characterized at each timepoint by culture-independent analysis of the 16S rRNA-encoding gene. RESULTS: Each baboon harbored a diverse vaginal microbiome. Interindividual variation exceeded intra-individual variation. Diversity declined over time in one baboon and showed mild fluctuations in the other two. There were no significant community differences from early to late post-LNG-IUS placement. CONCLUSIONS: The baboon vaginal microbiome is unique to each individual and is polymicrobial. In this pilot study, the vaginal microbiome remained stable from early to late post-LNG-IUS placement.
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Anticonceptivos Femeninos/farmacología , Dispositivos Intrauterinos Medicados , Levonorgestrel/farmacología , Microbiota/efectos de los fármacos , Papio anubis/microbiología , Vagina/efectos de los fármacos , Vagina/microbiología , Animales , Anticonceptivos Femeninos/administración & dosificación , Femenino , Levonorgestrel/administración & dosificación , Modelos Animales , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Análisis de Secuencia de ADN , Ultrasonografía , Útero/diagnóstico por imagenRESUMEN
Candidates for epilepsy surgery often use the word "hope" to express their attitudes and beliefs about surgery. However, studies suggest that hope has a multiplicity of meanings that are not well understood. The goal of this analysis was to evaluate whether Candidates for epilepsy surgery use hope language to express a traditional, expected optimism during presurgery interviews. We examined patients' uses of the word "hope" and its derivatives (hoping, hopeful, hopefully) through a secondary analysis of 37 interviews of adult patients prior to epilepsy surgery. Approximately 1/3 of all hope statements were coded as expressions of optimism, while 1/3 were not optimistic, and 1/3 had unclear meanings. In addition to traditionally optimistic uses of the term, other themes surrounding use of this word included ideas of dread, worry, uncertainty, and temporizing language. This information may help clinicians communicate more effectively with patients, enhancing the informed consent process for epilepsy surgery.
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Epilepsia/psicología , Epilepsia/cirugía , Conocimientos, Actitudes y Práctica en Salud , Lenguaje , Procedimientos Neuroquirúrgicos/métodos , Relaciones Médico-Paciente , Adulto , Anciano , Femenino , Humanos , Consentimiento Informado , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Genital Alphapapillomavirus (αPV) infections are one of the most common sexually transmitted human infections worldwide. Women infected with the highly oncogenic genital human papillomavirus (HPV) types 16 and 18 are at high risk for development of cervical cancer. Related oncogenic αPVs exist in rhesus and cynomolgus macaques. Here the authors identified 3 novel genital αPV types (PhPV1, PhPV2, PhPV3) by PCR in cervical samples from 6 of 15 (40%) wild-caught female Kenyan olive baboons (Papio hamadryas anubis). Eleven baboons had koilocytes in the cervix and vagina. Three baboons had dysplastic proliferative changes consistent with cervical squamous intraepithelial neoplasia (CIN). In 2 baboons with PCR-confirmed PhPV1, 1 had moderate (CIN2, n = 1) and 1 had low-grade (CIN1, n = 1) dysplasia. In 2 baboons with PCR-confirmed PhPV2, 1 had low-grade (CIN1, n = 1) dysplasia and the other had only koilocytes. Two baboons with PCR-confirmed PhPV3 had koilocytes only. PhPV1 and PhPV2 were closely related to oncogenic macaque and human αPVs. These findings suggest that αPV-infected baboons may be useful animal models for the pathogenesis, treatment, and prophylaxis of genital αPV neoplasia. Additionally, this discovery suggests that genital αPVs with oncogenic potential may infect a wider spectrum of non-human primate species than previously thought.
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Alphapapillomavirus/aislamiento & purificación , Enfermedades de los Monos/virología , Papio hamadryas , Displasia del Cuello del Útero/veterinaria , Neoplasias del Cuello Uterino/veterinaria , Alphapapillomavirus/clasificación , Alphapapillomavirus/genética , Animales , Cuello del Útero/química , Cuello del Útero/patología , ADN Viral/genética , Femenino , Humanos , Inmunohistoquímica/veterinaria , Antígeno Ki-67/análisis , Enfermedades de los Monos/patología , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/veterinaria , Infecciones por Papillomavirus/virología , Filogenia , Reacción en Cadena de la Polimerasa/veterinaria , Análisis de Secuencia de ADN/veterinaria , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Vagina/patologíaRESUMEN
OBJECTIVE: The aim of the current study was to quantify the head excursions of pediatric anthropomorphic test devices (ATDs) seated in rearward-facing child restraint system (CRS) models during rear impact sled tests and compare to roof heights of vehicles in the current fleet to assess the possibility of head contact against the vehicle roof. METHODS: Head excursions of ATDs seated in rearward-facing CRS models were analyzed from high-speed video data from 14 rear impact sled tests across two different series. Tests were conducted in rigidized vehicle seats from recent model year vehicles. Rearward-facing infant and convertible CRS models were tested with a variety of pediatric ATDs aged 12 months to 6 years in a variety of installation conditions (e.g., lower anchors or seat belt, anti-rotation features, etc). Maximum ATD head excursions in plane of the seatback were compared to previously measured roof heights of 87 different vehicles. RESULTS: The roof heights in all sedan seating positions (n = 58) and SUV/CUV/minivan seating positions (n = 60) were greater than the largest maximum ATD head excursions in plane of the seatback (792 mm). Head contact was possible in two of the pickup trucks which had roof heights of 730 and 775 mm. In all, 98% of vehicle seating positions measured in this study would accommodate all of the maximum ATD head excursions in plane of the seatback without contact. CONCLUSIONS: The risk of head contact against the vehicle interior roof appears low as maximum ATD head excursions in plane of the seatback were typically not great enough to reach the rooflines of the vehicles in the sample. Head contact appears possible in pickup trucks, where the window/roofline is directly behind the head restraint.
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Sistemas de Retención Infantil , Lactante , Niño , Humanos , Accidentes de Tránsito , Diseño de Equipo , Cinturones de Seguridad , Vehículos a Motor , Fenómenos Biomecánicos , Maniquíes , CabezaRESUMEN
The objective of this study was to compare the biological and economic efficiencies of 2 likely future pasture-based systems of milk production differing in overall stocking rate and concentrate supplementation level on a wetland drumlin soil in the Border Midlands Western region of Ireland. Physical performance data were obtained from a 3-yr systems comparison at Ballyhaise College, Co. Cavan, comparing 2 production systems: a high grass (HG) system (578 kg of concentrate/cow at 2.45 livestock units per hectare) and a high intensity (HI) system (1,365 kg of concentrate/cow at 2.92 livestock units/ha). Animal production data were analyzed using a mixed model, with feed system, year, and parity included as fixed effects in the final model. Feed system had a significant effect on all yield variables with higher yields in the HI system. Production system had no significant influence on reproductive performance. The Moorepark Dairy Systems Model, a stochastic budgetary simulation model, was used to simulate a model farm integrating biological data from each feed system to identify the economic effect of each system at 3 future milk prices of 22, 27, and 33 euro cents per liter (c/L). Two economic scenarios were investigated within the model: scenario 1 (S1) assumed fixed cow numbers (n=55 cows) and scenario 2 (S2) assumed fixed land area (n=40 ha). At a milk price of 27 or 33 c/L, profit per cow, per kilogram of milk solids, and per hectare were similar for HG and HI in S1 and higher for HI in S2. At a milk price of 22 c/L, all systems were unprofitable, with increased losses realized in the HI system (both S1 and S2) compared with the HG system. Pasture-based systems of milk production in the northern region of Ireland are capable of highly efficient and profitable milk production. Moreover, the efficacy of increased supplementation to remove the constraints of pasture seasonality will depend on the cost of supplementation and the price paid for additional milk produced.
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Industria Lechera/métodos , Humedales , Alimentación Animal/economía , Animales , Bovinos , Clima , Industria Lechera/economía , Femenino , Irlanda , Lactancia , Leche/economía , Modelos Económicos , Medición de RiesgoRESUMEN
OBJECTIVE: Some child restraint system (CRS) manufacturers specify a minimum distance between the CRS and the seatback, whereas others require that the CRS may contact the seatback but cannot be "braced"; however, few studies have investigated these interactions. Therefore, the aim was to investigate the interactions between the front row seat and rearward-facing CRS models with and without a support leg during frontal crashes. METHODS: Sled tests using the FMVSS 213 frontal crash pulse were performed with the Q1.5 and Q3 anthropomorphic test devices (ATDs) seated in rearward-facing infant and convertible CRS models, respectively. A front row vehicle seat was in front of the test bench in three track positions: brace, touch and gap. For the touch condition, the front row seat was translated aftward until the seatback contacted the CRS. For the brace condition, the front row seat was translated 20 mm aftward. For the gap condition, the front row seat was translated 50 mm forward. Each condition was tested with and without the support leg of the CRS. RESULTS: The tests with a support leg were associated with significantly (p = 0.007) lower resultant linear head acceleration 3 ms clip compared to the tests without a support leg, but the reduction of head injury criterion 15 ms (HIC15) was not significant (p = 0.057). The Q1.5 ATD in the rearward-facing infant CRS with a support leg had the lowest injury metrics for the touch and gap conditions, whereas the Q3 in the rearward-facing convertible CRS had the lowest head injury metrics for the brace condition. CONCLUSIONS: The use of a support leg provided a clear benefit in terms of reducing head injury metrics for the Q1.5 in the rearward-facing infant CRS, especially for the touch and gap conditions. The rearward-facing convertible CRS in the current study appears to benefit from being braced against the front row seat. However, further tests are required to allow further statistical comparisons and determine if these preliminary findings extend to other rearward-facing CRS models.
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Sistemas de Retención Infantil , Traumatismos Craneocerebrales , Niño , Lactante , Humanos , Accidentes de Tránsito , Diseño de Equipo , Fenómenos BiomecánicosRESUMEN
The NCI-MATCH was designed to characterize the efficacy of targeted therapies in histology-agnostic driver mutation-positive malignancies. Sub-protocols F and G were developed to evaluate the role of crizotinib in rare tumors that harbored either ALK or ROS1 rearrangements. Patients with malignancies that progressed following at least one prior systemic therapy were accrued to the NCI-MATCH for molecular profiling, and those with actionable ALK or ROS1 rearrangements were offered participation in sub-protocols F or G, respectively. There were five patients who enrolled on Arm F (ALK) and four patients on Arm G (ROS1). Few grade 3 or 4 toxicities were noted, including liver test abnormalities, and acute kidney injury. For sub-protocol F (ALK), the response rate was 50% (90% CI 9.8-90.2%) with one complete response among the 4 eligible patients. The median PFS was 3.8 months, and median OS was 4.3 months. For sub-protocol G (ROS1) the response rate was 25% (90% CI 1.3-75.1%). The median PFS was 4.3 months, and median OS 6.2 months. Data from 3 commercial vendors showed that the prevalence of ALK and ROS1 rearrangements in histologies other than non-small cell lung cancer and lymphoma was rare (0.1% and 0.4% respectively). We observed responses to crizotinib which met the primary endpoint for ALK fusions, albeit in a small number of patients. Despite the limited accrual, some of the patients with these oncogenic fusions can respond to crizotinib which may have a therapeutic role in this setting.
RESUMEN
RC-101 is a synthetic microbicide analog of retrocyclin, which has shown in vitro activity against X4 and R5 HIV-1. In an effort to develop a safe and effective RC-101 vaginal microbicide product, we assessed safety in ex vivo macaque and human models and efficacy using in vitro and ex vivo models. A polyvinyl-alcohol vaginal film containing RC-101 (100 µg/film) was developed. Formulation assessment was conducted by evaluating disintegration, drug content, mechanical properties, and stability. Efficacy was evaluated by in vitro peripheral blood mononuclear cells (PBMC) assay and ex vivo human ectocervical tissue explant model. Ex vivo safety studies were conducted by exposing RC-101 to an excised monkey reproductive tract and excised human ectocervical tissue. RC-101 100 µg films were shown to be safe to human and monkey tissue and effective against HIV-1 in vitro and ex vivo in human ectocervical tissue. The 90% inhibitory concentration (IC90) for RC-101 films at 2,000 µg (IC90=57.5 µM) using an ex vivo model was 10-fold higher than the IC90 observed using an in vitro model (IC90=5.0 µM). RC-101 films were stable for 1 month at 25°C, with in vitro bioactivity maintained for up to 6 months. RC-101 was developed in a quick-dissolve film formulation that was shown to be safe in an ex vivo model and effective in in vitro and ex vivo models. RC-101 film formulations were shown to maintain bioactivity for a period of 6 months. Findings from the present study contribute to the development of a safe and effective topical microbicide product.