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1.
Nature ; 568(7752): 360-363, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30996312

RESUMEN

Lightning is a dangerous yet poorly understood natural phenomenon. Lightning forms a network of plasma channels propagating away from the initiation point with both positively and negatively charged ends-called positive and negative leaders1. Negative leaders propagate in discrete steps, emitting copious radio pulses in the 30-300-megahertz frequency band2-8 that can be remotely sensed and imaged with high spatial and temporal resolution9-11. Positive leaders propagate more continuously and thus emit very little high-frequency radiation12. Radio emission from positive leaders has nevertheless been mapped13-15, and exhibits a pattern that is different from that of negative leaders11-13,16,17. Furthermore, it has been inferred that positive leaders can become transiently disconnected from negative leaders9,12,16,18-20, which may lead to current pulses that both reconnect positive leaders to negative leaders11,16,17,20-22 and cause multiple cloud-to-ground lightning events1. The disconnection process is thought to be due to negative differential resistance18, but this does not explain why the disconnections form primarily on positive leaders22, or why the current in cloud-to-ground lightning never goes to zero23. Indeed, it is still not understood how positive leaders emit radio-frequency radiation or why they behave differently from negative leaders. Here we report three-dimensional radio interferometric observations of lightning over the Netherlands with unprecedented spatiotemporal resolution. We find small plasma structures-which we call 'needles'-that are the dominant source of radio emission from the positive leaders. These structures appear to drain charge from the leader, and are probably the reason why positive leaders disconnect from negative ones, and why cloud-to-ground lightning connects to the ground multiple times.

2.
BMC Infect Dis ; 21(1): 880, 2021 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-34454462

RESUMEN

BACKGROUND: Ireland frequently reports the highest annual Crude Incidence Rates (CIRs) of cryptosporidiosis in the EU, with national CIRs up to ten times the EU average. Accordingly, the current study sought to examine the spatiotemporal trends associated with this potentially severe protozoan infection. METHODS: Overall, 4509 cases of infection from January 2008 to December 2017 were geo-referenced to a Census Small Area (SA), with an ensemble of geo-statistical approaches including seasonal decomposition, Local Moran's I, and space-time scanning used to elucidate spatiotemporal patterns of infection. RESULTS: One or more confirmed cases were notified in 3413 of 18,641 Census SAs (18.3%), with highest case numbers occurring in the 0-5-year range (n = 2672, 59.3%). Sporadic cases were more likely male (OR 1.4) and rural (OR 2.4), with outbreak-related cases more likely female (OR 1.4) and urban (OR 1.5). Altogether, 55 space-time clusters (≥ 10 confirmed cases) of sporadic infection were detected, with three "high recurrence" regions identified; no large urban conurbations were present within recurrent clusters. CONCLUSIONS: Spatiotemporal analysis represents an important indicator of infection patterns, enabling targeted epidemiological intervention and surveillance. Presented results may also be used to further understand the sources, pathways, receptors, and thus mechanisms of cryptosporidiosis in Ireland.


Asunto(s)
Criptosporidiosis , Criptosporidiosis/epidemiología , Brotes de Enfermedades , Femenino , Humanos , Incidencia , Irlanda/epidemiología , Masculino , Población Rural
3.
Phys Rev Lett ; 124(10): 105101, 2020 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-32216418

RESUMEN

We use the Low Frequency Array (LOFAR) to probe the dynamics of the stepping process of negatively charged plasma channels (negative leaders) in a lightning discharge. We observe that at each step of a leader, multiple pulses of vhf (30-80 MHz) radiation are emitted in short-duration bursts (<10 µs). This is evidence for streamer formation during corona flashes that occur with each leader step, which has not been observed before in natural lightning and it could help explain x-ray emission from lightning leaders, as x rays from laboratory leaders tend to be associated with corona flashes. Surprisingly, we find that the stepping length is very similar to what was observed near the ground, however with a stepping time that is considerably larger, which as yet is not understood. These results will help to improve lightning propagation models, and eventually lightning protection models.

4.
Diabet Med ; 35(6): 776-788, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29575241

RESUMEN

AIMS: To undertake a feasibility randomized controlled trial of supported self-management vs treatment as usual in a population of adults with obesity, Type 2 diabetes and an intellectual disability. METHODS: We conducted an individually randomized feasibility trial. Participants were adults aged >18 years with a mild or moderate intellectual disability, living in the community with Type 2 diabetes, on any therapy other than insulin. Participants had mental capacity to consent to research and the intervention. Inclusion criteria included HbA1c > 48 mmol/mol (6.5%), BMI >25 kg/m2 , or self-reported physical activity below national guideline levels. The experimental intervention was standardized supported self-management delivered by diabetes specialist nurses plus treatment as usual, compared with treatment as usual alone. Feasibility outcomes included: recruitment and retention; intervention acceptability and feasibility; data collection and completeness for physiological state and values for candidate primary outcomes (HbA1c and BMI). RESULTS: A total of 82 participants (89% of those contacted and eligible) were randomized. All supported self-management sessions were completed by 35/41 participants (85%); only four completed no sessions. Data on the follow-up candidate primary outcomes HbA1c and BMI were obtained for 75/82 (91%) and 77/82 participants (94%), respectively. The mean baseline HbA1c was 56±16.5 mmol/mol (7.3±1.5%) and the mean BMI was 34±7.6 kg/m2 . CONCLUSIONS: Adherence to supported self-management and willingness to have blood taken for outcome measurement was good. A definitive randomized controlled trial is feasible in this population. (Trial registration: Current Controlled Trials ISRCTN41897033).


Asunto(s)
Diabetes Mellitus Tipo 2/enfermería , Discapacidad Intelectual/complicaciones , Obesidad/complicaciones , Automanejo/métodos , Afecto , Presión Sanguínea/fisiología , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/psicología , Estudios de Factibilidad , Femenino , Hemoglobina Glucada/metabolismo , Visita Domiciliaria/estadística & datos numéricos , Humanos , Discapacidad Intelectual/enfermería , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Obesidad/enfermería , Apoyo Social , Encuestas y Cuestionarios
6.
J Viral Hepat ; 24(1): 53-58, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27502689

RESUMEN

Antiviral therapy for hepatitis B is effective and reduces the risk of progression to cirrhosis and liver cancer but is often required for an indefinite duration. Treatment adherence is important to prevent the development of resistance and optimize outcomes. Pharmacy adherence measures can be used to assess treatment adherence, with the medication possession ratio being less susceptible to bias than physician- or self-reported adherence. The aim of this study was to measure adherence in public hospital outpatients over a 3-year period and to examine factors associated with nonadherence. A retrospective study of pharmacy records of patients dispensed antiviral therapy for hepatitis B from four major hospitals in Melbourne between 2010 and 2013. Hospital record numbers were linked with and de-identified demographic information including age, sex, Indigenous status, country of birth, interpreter requirement, spoken language and postcode of residence. The medication possession ratio was the outcome measure with poor adherence defined <.90. Univariate logistic regression and multivariate logistic regression were performed to examine associations with nonadherence. Records of 1026 patients were included in the analysis. Twenty per cent of all participants met the definition of poor adherence. Significant factors affecting adherence included age <35 years (P=.002), hospital site and treatment by multiple doctors within shorter time periods. This is the largest study examining detailed factors associated with adherence to hepatitis B treatment. Understanding poor adherence in clinical settings, and the factors associated with lower adherence, is important to inform efforts towards promoting treatment adherence for hepatitis B.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis B/tratamiento farmacológico , Cumplimiento de la Medicación , Adulto , Anciano , Anciano de 80 o más Años , Australia , Femenino , Hospitales Públicos , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Estudios Retrospectivos , Adulto Joven
7.
Epidemiol Infect ; 145(1): 95-105, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27609320

RESUMEN

Ireland reports the highest incidence of verotoxigenic Escherichia coli (VTEC) infection in Europe. This study investigated potential risk factors for confirmed sporadic and outbreak primary VTEC infections during 2008-2013. Overall, 989 VTEC infections including 521 serogroup O157 and 233 serogroup O26 were geo-referenced to 931 of 18 488 census enumeration areas. The geographical distribution of human population, livestock, unregulated groundwater sources, domestic wastewater treatment systems (DWWTS) and a deprivation index were examined relative to notification of VTEC events in 524 of 6242 rural areas. Multivariate modelling identified three spatially derived variables associated with VTEC notification: private well usage [odds ratio (OR) 6·896, P < 0·001], cattle density (OR 1·002, P < 0·001) and DWWTS density (OR 0·978, P = 0·002). Private well usage (OR 18·727, P < 0·001) and cattle density (OR 1·001, P = 0·007) were both associated with VTEC O157 infection, while DWWTS density (OR 0·987, P = 0·028) was significant within the VTEC O26 model. Findings indicate that VTEC infection in the Republic of Ireland is particularly associated with rural areas, which are associated with a ubiquity of pathogen sources (cattle) and pathways (unregulated groundwater supplies).


Asunto(s)
Infecciones por Escherichia coli/epidemiología , Escherichia coli Shiga-Toxigénica/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Crianza de Animales Domésticos , Animales , Bovinos , Niño , Preescolar , Drenaje de Agua , Infecciones por Escherichia coli/microbiología , Femenino , Humanos , Lactante , Recién Nacido , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Población Rural , Adulto Joven
8.
J Urol ; 196(1): 202-6, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26874316

RESUMEN

PURPOSE: Pediatric tissues are exquisitely sensitive to ionizing radiation from diagnostic studies and therapies involving fluoroscopy. We prospectively monitored radiation exposure in our pediatric urology patients during fluoroscopy guided operative procedures with single point dosimeters to quantify radiation dose. MATERIALS AND METHODS: Children undergoing fluoroscopy guided urological procedures were prospectively enrolled in the study from 2013 to 2015. Single point dosimeters were affixed to skin overlying the procedural site for the durations of the procedures to record dosimetry data. Patient demographics, procedural variables and fluoroscopic settings were recorded. RESULTS: A total of 78 patients underwent 96 procedures, including retrograde pyelography, ureteral stent insertion, ureteroscopy and percutaneous nephrolithotomy. Median patient age was 12 years (range 0.3 to 17) and median body mass index percentile for age was 70.7 (1.0 to 99.1). Median skin entrance radiation dose for all procedures performed was 0.56 mGy. Median dosages associated with the 29 diagnostic procedures and 49 definitive interventions were 0.6 mGy (mean 0.8, range 0.1 to 2.2) and 0.7 mGy (1.1, 0.0 to 5.5), respectively. The dose associated with the 18 procedures of temporization was significantly higher by comparison (median 1.0 mGy, mean 2.6, range 0.1 to 10.7, p = 0.02). CONCLUSIONS: Pediatric radiation exposure is not insignificant during urological procedures. Further multi-institutional work would provide context for our findings. Protocols to optimize fluoroscopic settings and minimize patient exposure, and guidelines for radiation based imaging should have a key role in all pediatric radiation safety initiatives.


Asunto(s)
Técnicas de Diagnóstico Urológico , Seguridad del Paciente , Dosis de Radiación , Exposición a la Radiación , Monitoreo de Radiación , Procedimientos Quirúrgicos Urológicos , Adolescente , Niño , Preescolar , Femenino , Fluoroscopía , Humanos , Lactante , Recién Nacido , Masculino , Pediatría , Estudios Prospectivos , Urología
9.
Diabetes Obes Metab ; 18(1): 64-71, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26434564

RESUMEN

AIMS: To develop and validate a model to simulate progression of diabetic kidney disease (DKD) from early onset until end-stage renal disease (ESRD), and to assess the effect of renin-angiotensin system (RAS) intervention in early, intermediate and advanced stages of DKD. METHODS: We used data from the BENEDICT, IRMA-2, RENAAL and IDNT trials that assessed effects of RAS intervention in patients with type 2 diabetes. We built a model with discrete disease stages based on albuminuria and estimated glomerular filtration rate (eGFR). Using survival analyses, we assessed the effect of RAS intervention on delaying ESRD in early [eGFR>60 ml/min/1.73 m(2) and albumin:creatinine ratio (ACR) <30 mg/g], intermediate (eGFR 30-60 ml/min/1.73 m(2) or ACR 30-300 mg/g) and advanced (eGFR <30 ml/min/1.73 m(2) or ACR >300 mg/g) stages of DKD for patients in different age groups. RESULTS: For patients at early, intermediate and advanced stage of disease, whose mean age was 60 years and who received placebo, the median time to ESRD was 21.4, 10.8 and 4.7 years, respectively. RAS intervention delayed the predicted time to ESRD by 4.2, 3.6 and 1.4 years, respectively. The benefit of early RAS intervention was more pronounced in younger patients; for example, for patients with a mean age of 45 years, RAS intervention at early, intermediate or advanced stage delayed ESRD by 5.9, 4.0 and 1.1 years versus placebo. CONCLUSIONS: RAS intervention early in the course of proteinuric DKD is more beneficial than late intervention in delaying ESRD.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Fallo Renal Crónico/prevención & control , Tiempo de Tratamiento , Factores de Edad , Anciano , Albúminas/análisis , Albuminuria/complicaciones , Creatinina/análisis , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/patología , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/etiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sistema Renina-Angiotensina/efectos de los fármacos , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo
10.
Diabetes Obes Metab ; 18(11): 1120-1127, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27337598

RESUMEN

AIMS: To predict individualized treatment effects of angiotensin receptor blockers (ARBs) on cardiovascular and renal complications in order to help clinicians and patients assess the benefit of treatment (or adherence) and estimate remaining disease risk. MATERIALS AND METHODS: In patients with diabetic nephropathy, the 3-year treatment effect of ARBs was predicted in terms of absolute risk reduction (ARR) for end-stage renal disease (ESRD) and cardiovascular disease (CVD; i.e. myocardial infarction, stroke, hospitalization for heart failure) and all-cause mortality. Competing-risk-adjusted proportional hazard models were developed based on the Irbesartan Diabetic Nephropathy Trial (IDNT) and externally validated in the Reduction of Endpoints NIDDM with Angiotensin II Antagonist Losartan (RENAAL) trial. RESULTS: Predictors included in the model were age, sex, smoking sex, systolic blood pressure, urinary albumin/creatinine ratio, estimated glomerular filtration rate, albumin and phosphorus. The median predicted 3-year risk without treatment was 6.0% for ESRD and 28.0% for CVD and mortality. The median [interquartile range (IQR)] predicted 3-year ARR was 1.2 (0.4-3.1)% for ESRD and 2.2 (1.8-2.6)% for CVD and mortality, resulting in a combined ARR of 3.4 (2.4-5.5)%. The remaining disease risk was 4.7 (IQR 1.7-12.8)% for ESRD and 25.8% (IQR 20.3-31.9)% for CVD and mortality. CONCLUSIONS: The combined effects of ARBs on ESRD and CVD and mortality in patients with diabetic nephropathy vary considerably between patients. A substantial proportion of patients remain at high risk for both outcomes despite ARB treatment.


Asunto(s)
Antagonistas de Receptores de Angiotensina/farmacología , Sistema Cardiovascular/efectos de los fármacos , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/tratamiento farmacológico , Individualidad , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/tratamiento farmacológico , Riñón/efectos de los fármacos , Adulto , Anciano , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/prevención & control , Sistema Cardiovascular/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/fisiopatología , Femenino , Humanos , Riñón/fisiopatología , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Sistema Renina-Angiotensina/efectos de los fármacos , Estudios Retrospectivos , Medición de Riesgo , Resultado del Tratamiento
11.
Conserv Biol ; 28(1): 159-68, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24033371

RESUMEN

Electrocution on overhead power structures negatively affects avian populations in diverse ecosystems worldwide, contributes to the endangerment of raptor populations in Europe and Africa, and is a major driver of legal action against electric utilities in North America. We investigated factors associated with avian electrocutions so poles that are likely to electrocute a bird can be identified and retrofitted prior to causing avian mortality. We used historical data from southern California to identify patterns of avian electrocution by voltage, month, and year to identify species most often killed by electrocution in our study area and to develop a predictive model that compared poles where an avian electrocution was known to have occurred (electrocution poles) with poles where no known electrocution occurred (comparison poles). We chose variables that could be quantified by personnel with little training in ornithology or electric systems. Electrocutions were more common at distribution voltages (≤ 33 kV) and during breeding seasons and were more commonly reported after a retrofitting program began. Red-tailed Hawks (Buteo jamaicensis) (n = 265) and American Crows (Corvus brachyrhynchos) (n = 258) were the most commonly electrocuted species. In the predictive model, 4 of 14 candidate variables were required to distinguish electrocution poles from comparison poles: number of jumpers (short wires connecting energized equipment), number of primary conductors, presence of grounding, and presence of unforested unpaved areas as the dominant nearby land cover. When tested against a sample of poles not used to build the model, our model distributed poles relatively normally across electrocution-risk values and identified the average risk as higher for electrocution poles relative to comparison poles. Our model can be used to reduce avian electrocutions through proactive identification and targeting of high-risk poles for retrofitting.


Asunto(s)
Aves/lesiones , Conservación de los Recursos Naturales , Traumatismos por Electricidad/veterinaria , Modelos Biológicos , Animales , California/epidemiología , Traumatismos por Electricidad/epidemiología , Traumatismos por Electricidad/etiología , Electricidad , Modelos Logísticos , Estaciones del Año , Especificidad de la Especie
12.
Intern Med J ; 44(8): 779-84, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24893756

RESUMEN

BACKGROUND: Venous thromboembolism (VTE) is a well-recognised extra-intestinal manifestation of inflammatory bowel disease (IBD). Despite the widespread support for anticoagulant prophylaxis in hospitalised IBD patients, the utilisation and efficacy in clinical practice are unknown. AIMS: The aim of this study was to assess the prevalence and clinical features of VTE among hospitalised IBD patients and ascertain whether appropriate thromboprophylaxis had been administered. METHODS: All patients with a discharge diagnosis of Crohn disease or ulcerative colitis and VTE were retrospectively identified using International Classification of Diseases, tenth revision codes from medical records at our institution from July 1998 to December 2009. Medical records were then reviewed for clinical history and utilisation of thromboprophylaxis. Statistical analysis was performed by Mann-Whitney test and either χ(2) tests or Fisher's exact tests. RESULTS: Twenty-nine of 3758 (0.8%) IBD admissions suffered VTE, 13 preadmission and 16 during admission. Of these 29 admissions (in 25 patients), 24% required intensive care unit and 10% died. Of the 16 venous thrombotic events that occurred during an admission, eight (50%) did not receive anticoagulant thromboprophylaxis and eight (50%) occurred despite thromboprophylaxis. Most thromboembolism despite prophylaxis occurred post-intestinal resection (n = 5, 63%). CONCLUSION: Thromboprophylaxis is underutilised in half of IBD patients suffering VTE. Prescription of thromboprophylaxis for all hospitalised IBD patients, including dual pharmacological and mechanical prophylaxis in postoperative patients, may lead to a reduction in this preventable complication of IBD.


Asunto(s)
Anticoagulantes/uso terapéutico , Hospitalización/estadística & datos numéricos , Enfermedades Inflamatorias del Intestino/complicaciones , Pacientes Internos , Terapia Trombolítica/estadística & datos numéricos , Tromboembolia Venosa/prevención & control , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Enfermedades Inflamatorias del Intestino/terapia , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Terapia Trombolítica/métodos , Resultado del Tratamiento , Tromboembolia Venosa/etiología , Victoria/epidemiología
13.
Sci Total Environ ; 922: 171112, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38387579

RESUMEN

Consolidation of multi-domain risk management research is essential for strategies facilitating the concerted government (educational) and population-level (behavioural) actions required to reduce microbial private groundwater contamination. However, few studies to date have synthesised this literature or sought to ascertain the causal generality and extent of supply contamination and preventive responses. In light of the Republic of Ireland (ROI) and Ontario's high reliance and research focus on private wells and consequent utility for empirical comparison, a scoping review of pertinent literature (1990-2022) from both regions was undertaken. The SPICE (Setting, Perspective, Intervention, Comparison, Evaluation) method was employed to inform literature searches, with Scopus and Web of Science selected as primary databases for article identification. The review identified 65 relevant articles (Ontario = 34, ROI = 31), with those investigating well user actions (n = 22) and groundwater quality (n = 28) the most frequent. A markedly higher pooled proportion of private supplies in the ROI exhibited microbial contamination (38.3 % vs. 4.1 %), despite interregional similarities in contamination drivers (e.g., weather, physical supply characteristics). While Ontarian well users demonstrated higher rates of historical (≥ 1) and annual well testing (90.6 % vs. 71.1 %; 39.1 % vs. 8.6 %) and higher rates of historical well treatment (42.3 % vs. 24.3 %), interregional levels of general supply knowledge were analogous (70.7 % vs. 71.0 %). Financial cost, organoleptic properties and residence on property during supply construction emerged as predictors of cognition and behaviour in both regions. Review findings suggest broad interregional similarities in drivers of supply contamination and individual-level risk mitigation, indicating that divergence in contamination rates may be attributable to policy discrepancies - particularly well testing incentivisation. The paucity of identified intervention-oriented studies further highlights the importance of renewed research and policy agendas for improved, targeted well user outreach and incentivised, convenience-based services promoting routine supply maintenance.


Asunto(s)
Agua Subterránea , Abastecimiento de Agua , Medición de Riesgo , Gestión de Riesgos , Irlanda , Pozos de Agua
14.
Heliyon ; 10(15): e34976, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39170449

RESUMEN

Objective: Ovarian cancer is a lethal gynaecological malignancy with unsatisfactory 5 year survival rates of 30-50 %. Cell immunotherapy is a promising new cancer treatment where immune cells, such as Natural Killer (NK) cells, are administered to enable the patient to fight cancer through direct cytotoxicity. NK cells orchestrate an adaptive immune response by enabling the release of tumour antigens. NK cell cytotoxicity and effector responses are largely driven by TRAIL engagement. In this study we investigated the cytotoxic potential of a human NK cell line that were modified to express a potent DR5 specific TRAIL variant. We hypothesised that this modification would enhance NK cell cytotoxicity against TRAIL sensitive and resistant ovarian cancer cell lines in vitro. Methods: KHYG-1 human NK cells were modified with a TRAIL variant targeting DR5 (TRAILv-KHYG-1). Human ovarian cancer cell lines, OVCAR-3 and SKOV-3, were cultured with modified or non-modified NK cells at different effector:target (E:T) ratios for 4 or 16 h. Apoptosis was assessed by Annexin-APC and 7-AAD and measured using flow cytometry. Apoptotic cells were defined as annexin V 7-AAD double positive. Cytokine expression was measured by multiplex ELISA, and analysed by flow cytometry. Results: Modified and non-modified NK cells significantly reduced OVCAR-3 cell viability as compared to OVCAR-3 cells that were cultured alone after 4 and 16 h treatment. OVCAR-3 cell viability was reduced after treatment with 1:1 E:T ratio with TRAILv-KHYG-1 cells after 16 h. On the contrary, neither NK cell line had any effect of SKOV-3 cell viability despite SKOV-3 cells having more DR5 surface expression compared to OVCAR-3 cells. Conclusions: TRAILv-KHYG-1 cells significantly reduced OVCAR-3 cell viability as compared to non-modified NK cells. However, no significant reduction in viability was observed when SKOV-3 cell were cultured with either NK cells, despite having more DR5 surface expression compared to OVCAR-3 cells. These data indicate that mechanisms other than DR5 expression drive TRAIL resistance in ovarian cancer.

15.
Eur J Neurol ; 20(1): 71-8, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22681045

RESUMEN

BACKGROUND AND PURPOSE: Intracranial haemorrhage in neurosarcoidosis (NS-ICH) is rare, poorly understood and the diagnosis of NS may not be immediately apparent. METHODS: The clinical features of three new NS-ICH cases are described including new neuropathological findings and collated with cases from a systematic literature review. CASES: (i) A 41-year-old man with headaches, hypoandrogenism and encephalopathy developed a cerebellar haemorrhage. He had neuropathological confirmation of NS with biopsy-proven angiocentric granulomata and venous disruption. He responded to immunosuppressive therapy. (ii) A 41-year-old man with no history of hypertension was found unconscious. A subsequently fatal pontine haemorrhage was diagnosed. Liver biopsy revealed sarcoid granulomas. (iii) A 36-year-old man with raised intracranial pressure headaches presented with a seizure and a frontal haemorrhage. Hilar lymph node biopsy confirmed sarcoidosis, and he was treated successfully. Systematic review: Twelve other published cases were identified and collated with our cases. Average age was 36 years and M:F = 2.3:1; 46% presented with neurological symptoms and 31% had CNS-isolated disease. Immediate symptoms of ICH were acute/worsening headache or seizures (60%). ICH was supratentorial (62%), infratentorial (31%) or subarachnoid (7%). Forty percent had definite NS, 53% probable NS and 7% possible NS (Zajicek criteria). Antigranulomatous/immunosuppressive therapy regimens varied and 31% died. CONCLUSIONS: This series expands our knowledge of the pathology of NS-ICH, which may be of arterial or venous origin. One-third have isolated NS. Clinicians should consider NS in young-onset ICH because early aggressive antigranulomatous therapy may improve outcome.


Asunto(s)
Enfermedades del Sistema Nervioso Central/complicaciones , Hemorragias Intracraneales/diagnóstico , Hemorragias Intracraneales/etiología , Sarcoidosis/complicaciones , Adulto , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos X
16.
Intern Med J ; 43(12): 1293-303, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23734944

RESUMEN

BACKGROUND: Emergency department (ED) crowding caused by access block is an increasing public health issue and has been associated with impaired healthcare delivery, negative patient outcomes and increased staff workload. AIM: To investigate the impact of opening a new ED on patient and healthcare service outcomes. METHODS: A 24-month time series analysis was employed using deterministically linked data from the ambulance service and three ED and hospital admission databases in Queensland, Australia. RESULTS: Total volume of ED presentations increased 18%, while local population growth increased by 3%. Healthcare service and patient outcomes at the two pre-existing hospitals did not improve. These outcomes included ambulance offload time: (Hospital A PRE: 10 min, POST: 10 min, P < 0.001; Hospital B PRE: 10 min, POST: 15 min, P < 0.001); ED length of stay: (Hospital A PRE: 242 min, POST: 246 min, P < 0.001; Hospital B PRE: 182 min, POST: 210 min, P < 0.001); and access block: (Hospital A PRE: 41%, POST: 46%, P < 0.001; Hospital B PRE: 23%, POST: 40%, P < 0.001). Time series modelling indicated that the effect was worst at the hospital furthest away from the new ED. CONCLUSIONS: An additional ED within the region saw an increase in the total volume of presentations at a rate far greater than local population growth, suggesting it either provided an unmet need or a shifting of activity from one sector to another. Future studies should examine patient decision making regarding reasons for presenting to a new or pre-existing ED. There is an inherent need to take a 'whole of health service area' approach to solve crowding issues.


Asunto(s)
Ambulancias , Bases de Datos Factuales/tendencias , Atención a la Salud/tendencias , Servicios Médicos de Urgencia/tendencias , Servicio de Urgencia en Hospital/tendencias , Adolescente , Adulto , Ambulancias/normas , Atención a la Salud/normas , Servicios Médicos de Urgencia/normas , Servicio de Urgencia en Hospital/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Carga de Trabajo/normas , Adulto Joven
17.
Sci Rep ; 13(1): 14485, 2023 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-37660180

RESUMEN

We have used the LOw-Frequency ARray (LOFAR) to search for the growing tip of an intra-cloud (IC) positive leader. Even with our most sensitive beamforming method, where we coherently add the signals of about 170 antenna pairs, we were not able to detect any emission from the tip. Instead, we put constraints on the emissivity of very-high frequency (VHF) radiation from the tip at 0.5 pJ/MHz at 60 MHz, integrated over 100 ns. The limit is independent on whether this emission is in the form of short pulses or continuously radiating. The non-observation of VHF radiation from intra-cloud positive leaders implies that they proceed in an extremely gradual process, which is in sharp contrast with the observations of other parts of a lightning discharge.

18.
Epidemiol Psychiatr Sci ; 32: e58, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37721170

RESUMEN

AIMS: There is clear evidence that installing safety barriers is effective in preventing jumping suicides from high-risk bridges with only moderate displacement to other nearby bridges. However, the impact of barriers on jumping suicides across broader geographical areas is not well understood. We examined patterns in jumping suicides across the state of Victoria, Australia, after a safety barrier was installed at the West Gate Bridge which, before the installation of the barrier, was the site of approximately 40% of Victoria's jumping suicides. METHODS: We used negative binomial regression analyses on Victorian data from 2000 to 2019 to compare rates of jumping suicides at the West Gate Bridge, other bridges and non-bridge jumping locations before, during and after the West Gate Bridge barrier installation. We conducted linear regression analyses to examine whether the distance travelled from the deceased's usual residence to the location of their jumping suicide changed between the before, during and after barrier installation periods. RESULTS: After installation of the barrier, there were no jumping suicides at the West Gate Bridge (rate ratio [RR] = 0.00, 95% credible intervals [95% Cr] = 0.00-0.0001) and there was strong evidence that the rate of jumping suicides at all locations declined by 65% (RR = 0.35, 95% Cr = 0.22-0.54). At other bridges, there was also evidence of a reduction (RR = 0.31, 95% Cr = 0.11-0.70), but there was no evidence of a change at non-bridge locations (RR = 0.74, 95% Cr = 0.39-1.30). CONCLUSION: After installation of the safety barrier at the West Gate Bridge, jumping suicide in Victoria decreased overall and at other bridges, and did not appear to change at non-bridge locations. Our findings show that when barriers are installed at a site responsible for a disproportionately high number of jumping suicides, they are not only highly effective at the site where the barriers are installed but can also have a prevention impact beyond the immediate locale at similar sites.


Asunto(s)
Suicidio , Humanos , Victoria , Viaje
19.
Arch Suicide Res ; 27(4): 1312-1338, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36237124

RESUMEN

OBJECTIVE: Some countries have implemented systems to monitor suicides in real-time. These systems differ because of the various ways in which suicides are identified and recorded. The main objective of this study was to conduct an international comparison of major real-time suicide mortality surveillance systems to identify joint strengths, challenges, and differences, and thereby inform best-practice criteria at local, national, and international levels. METHODS: Five major real-time suicide mortality surveillance systems of various coverage levels were identified and selected for review via an internet-based scoping exercise and prior knowledge of existing systems. Key information including the system components and practices was collated from those organizations that developed and operate each system using a structured template. The information was narratively and critically synthesized to determine similarities and differences between the systems. RESULTS: The comparative review of the five established real-time suicide surveillance systems revealed more commonalities than differences overall. Commonalities included rapid, routine surveillance based on minimal, provisional data to facilitate timely intervention and postvention efforts. Identified differences include the timeliness of case submission and system infrastructure. CONCLUSION: The recommended criteria could promote replicable components and practices in real-time suicide surveillance while offering flexibility in adapting to regional/local circumstances and resource availability.HIGHLIGHTSEvidence-informed recommendations for current best practice in real-time suicide surveillance.Proposed comprehensive framework can be adapted based on available resources and capacity.Real-time suicide mortality data facilitates rapid data-driven decision-making in suicide prevention.

20.
Ecol Appl ; 22(3): 894-908, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22645819

RESUMEN

The restoration of cleared dry forest represents an important opportunity to sequester atmospheric carbon. In order to account for this potential, the influences of climate, soils, and disturbance need to be deciphered. A data set spanning a region defined the aboveground biomass of mulga (Acacia aneura) dry forest and was analyzed in relation to climate and soil variables using a Bayesian model averaging procedure. Mean annual rainfall had an overwhelmingly strong positive effect, with mean maximum temperature (negative) and soil depth (positive) also important. The data were collected after a recent drought, and the amount of recent tree mortality was weakly positively related to a measure of three-year rainfall deficit, and maximum temperature (positive), soil depth (negative), and coarse sand (negative). A grazing index represented by the distance of sites to watering points was not incorporated by the models. Stark management contrasts, including grazing exclosures, can represent a substantial part of the variance in the model predicting biomass, but the impact of management was unpredictable and was insignificant in the regional data set. There was no evidence of density-dependent effects on tree mortality. Climate change scenarios represented by the coincidence of historical extreme rainfall deficit with extreme temperature suggest mortality of 30.1% of aboveground biomass, compared to 21.6% after the recent (2003-2007) drought. Projections for recovery of forest using a mapping base of cleared areas revealed that the greatest opportunities for restoration of aboveground biomass are in the higher-rainfall areas, where biomass accumulation will be greatest and droughts are less intense. These areas are probably the most productive for rangeland pastoralism, and the trade-off between pastoral production and carbon sequestration will be determined by market forces and carbon-trading rules.


Asunto(s)
Agricultura , Biomasa , Sequías , Ecosistema , Árboles , Clima , Conservación de los Recursos Naturales/métodos , Monitoreo del Ambiente/métodos , Modelos Biológicos , Queensland , Lluvia , Factores de Tiempo
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