Prospective migrants to countries where the incidence of tuberculosis (TB) is low (low-incidence countries) receive TB screening; however, screening for latent TB infection (LTBI) before immigration ...is rare. We evaluated the cost-effectiveness of mandated and sponsored preimmigration LTBI screening for migrants to low-incidence countries. We used discrete event simulation to model preimmigration LTBI screening coupled with postarrival follow-up and treatment for those who test positive. Preimmigration interferon-gamma release assay screening and postarrival rifampin treatment was preferred in deterministic analysis. We calculated cost per quality-adjusted life-year gained for migrants from countries with different TB incidences. Our analysis provides evidence of the cost-effectiveness of preimmigration LTBI screening for migrants to low-incidence countries. Coupled with research on sustainability, acceptability, and program implementation, these results can inform policy decisions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The increasing need to reduce damage and downtime in modern buildings has led to the development of a low‐damage design philosophy, where the earthquake loads can be resisted with damage confined to ...easily replaceable components. Post‐tensioned (PT) concrete walls have emerged as a popular low‐damage structural system that have been implemented in a range of buildings. In order to provide essential evidence to support the development of low‐damage concrete structures, a system‐level shake‐table test was conducted on a two‐storey low‐damage concrete wall building implementing state‐of‐art design concepts. The test building included PT rocking walls that provide the primary lateral‐load resistance in both directions, a frame that utilized slotted beam connections, and a range of alternative energy dissipation devices that were installed at wall base or/and beam‐column joints. The building was subjected to 39 tests with a range of intensity ground motions, incorporating both unidirectional and bidirectional ground motions on the structure with different combinations of wall strength and energy dissipating devices. The building performed exceptionally well during the intense series of tests, confirming the suitability of both the design methods and the connection detailing implemented. The building achieved an immediate occupancy performance objective even when subjected to maximum considered earthquake hazard shaking. The building exhibited only minor damage at the conclusion of testing, with distributed cracking in the floors and cosmetic spalling in the wall toes that did not compromise structural capacity or integrity and could be easily repaired with minimal disruption. The test has provided a rich dataset that is available for further analysis of the building response and validation of design methods and numerical models.
The possibility of pain occurring in animals is often accepted if various criteria are fulfilled. These criteria include prolonged grooming or rubbing at the site of a wound or tissue damage, or ...other behaviour involving the site of damage. We also expect to see a reduction in such activities if a local anaesthetic is applied. Here, we report on an experiment that applied caustic soda, a known irritant in humans, to one eyestalk of the glass prawn. This caused immediate escape responses and then nipping and picking at the treated eyestalk rather than at the untreated eyestalk. Prior application of a local anaesthetic reduced the amount of directed behaviour. However, the local anaesthetic also appeared to be an irritant as it too caused immediate escape responses and directed behaviour to the eyestalk. The results provide further support to the idea that these animals can experience pain. Acceptance of the possibility of pain in animals usually requires that various criteria are fulfilled. One such criterion is that a noxious stimulus or wound would elicit directed rubbing or grooming at the site of the stimulus. There is also an expectation that local anaesthetics would reduce these responses to damage. These expectations have been fulfilled in decapod crustaceans but there has been criticism of a lack of replication. Here, we report an experiment on the effects of a noxious chemical, sodium hydroxide, applied to one eyestalk of the glass prawn. This caused an immediate escape tail-flick response. It then caused nipping and picking with the chelipeds at the treated eyestalk but much less so at the alternative eyestalk. Prior treatment with benzocaine also caused an immediate tail-flick and directed behaviour, suggesting that this agent is aversive. Subsequently, however, it reduced the directed behaviour caused by caustic soda. We thus demonstrated responses that are consistent with the idea of pain in decapod crustaceans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Lessons Learned
Due to evolving imaging criteria in brain tumors and variation in magnetic resonance imaging evaluation, it is not ideal to use response rate as a primary objective. Future studies ...involving antiangiogenic agents should use overall survival.
Disease‐expected toxicities should be considered when defining the clinical significance of an adverse event. For example, vascular thromboembolic events are common in brain tumor patients and should not be attributed to the study drug in the safety analysis.
Background
Recurrent malignant glioma (rMG) prognosis is poor, with a median patient survival of 3–11 months with bevacizumab (BEV)‐containing regimens. BEV in rMG has 6‐month progression free survival (PFS‐6) of ∼40% and an objective response rate of 21.2%. BEV‐containing regimens improve PFS‐6 to 42.6%–50.3%, indicating that BEV combination therapies may be superior to single agent. Rilotumumab, a hepatocyte growth factor (HGF) antibody, inhibits angiogenesis and expression of angiogenic autocrine factors (e.g., vascular endothelial growth factor VEGF) by c‐Met inhibition. Combination of rilotumumab with BEV to block vascular invasion and tumor proliferation may synergistically inhibit tumor growth.
Methods
Thirty‐six BEV‐naïve rMG subjects received rilotumumab (20 mg/kg and BEV (10 mg/kg) every 2 weeks. Endpoints included objective response rate (using Response Assessment in Neuro‐Oncology RANO criteria), PFS‐6, overall survival (OS), and toxicity.
Results
Median patient follow‐up was 65.0 months. Objective response rate was 27.8% (95% confidence interval CI: 15.7%–44.1%). Median OS was 11.2 months (95% CI: 7–17.5). PFS‐6 was 41.7% (95% CI: 25.6%–57.0%). Most frequent treatment‐related grade ≤2 events included weight gain, fatigue, allergic rhinitis, and voice alteration; grade ≥3 events included venous thromboembolism (four patients), including one death from pulmonary embolism.
Conclusion
Rilotumumab with BEV did not significantly improve objective response compared with BEV alone, and toxicity may preclude the use of rilotumumab in combination BEV regimens.
经验获取
• 由于脑肿瘤影像标准的不断发展以及磁共振影像评估的变化,以缓解率作为主要指标不够理想。未来有关抗血管生成药物的研究应使用总生存期。
• 在界定不良事件的临床意义时,应考虑疾病的预期毒性。例如,血管血栓栓塞事件在脑肿瘤患者中常见,做安全性分析时不应归因于研究药物。
摘要
背景. 复发性恶性胶质瘤(rMG)预后较差,采用含贝伐单抗(BEV)的治疗方案时,患者生存期中位数为3~11个月。BEV在治疗rMG患者中,6个月无进展生存期(PFS‐6)的比例约40%,客观缓解率为21.2%。含BEV的治疗方案将PFS‐6提高至42.6%~50.3%,提示BEV联合治疗可能优于单药治疗。Rilotumumab是一种肝细胞生长因子(HGF)抗体,通过c‐Met抑制剂抑制血管生成及血管生成自分泌因子如血管内皮生长因子(VEGF)的表达。Rilotumumab联合BEV阻断血管浸润和肿瘤增殖,可能协同抑制肿瘤生长。
方法. 36例初治rMG受试者每2周接受一次rilotumumab(20 mg/kg)和BEV(10 mg/kg)治疗。终点包括客观缓解率利用神经肿瘤临床疗效评估(RANO)标准、PFS‐6、总生存期(OS)及毒性。
结果. 中位随访65.0个月。客观缓解率为27.8%95%置信区间(CI):15.7%–44.1%。中位OS为11.2个月(95%CI:7–17.5)。PFS‐6为41.7% (95% CI:25.6%–57.0%)。最常见的与治疗相关的 ≤2级事件包括体重增加、乏力、变应性鼻炎和声音改变; ≥3级事件包括静脉血栓栓塞(4例),其中1例死于肺栓塞。
结论 与BEV单药治疗相比,rilotumumab联合BEV不能明显改善客观缓解率,而且毒性可能会阻碍rilotumumab与BEV联合治疗方案。
This paper introduces a framework to estimate the seismic response of buildings at a regional scale by using representative
indicator buildings
. A robust database of buildings is required in the ...proposed framework to provide high-level structural and site information of the buildings. In this study, a database of 234 reinforced concrete buildings with five or more stories located in the central business district of Wellington, New Zealand was selected as a case study. In a prior phase of the research, the buildings were clustered into typologically similar clusters and eight representative
indicator buildings
were selected, where an
indicator building
was the closest building to the mean cluster structural and site characteristics. In this work, the concept of using
indicator buildings
to estimate building response across each cluster is investigated. First, three-dimensional structural models of each of the eight selected
indicator buildings
from the Wellington database were developed using the opensource structural analysis program OpenSeesPy. Five models were developed for each indicator building: one nonlinear model, one linear model, and three linear supplementary models where the effective stiffness of the structural members were modified to represent the period range of all buildings across a given cluster. The supplementary models were used to develop a period correction relationship to modify the estimated drifts based on the spectral shape of the imposed ground motion. Ground motions from the 2016 Kaikōura and 2013 Seddon earthquakes in New Zealand, as well as the 1995 Kobe earthquake in Japan, were selected to evaluate the proposed framework. The relationships between predicted elastic and inelastic drifts were explored, and polynomial regression models were investigated to provide drift correction accounting for the spectral shape of the three earthquakes. Finally, the efficacy of the proposed framework in estimating the response of all buildings across all clusters and the applicability of this framework as a near real-time impact tool were demonstrated using post-earthquake damage reports from the Kaikōura and Seddon earthquakes.
Actuarial scales like the Static-99R are widely used to predict an individual’s risk of sexual recidivism. However, current actuarial scales only provide rates of detected sex offenses over 10-year ...follow-up and do not account for all recidivism risk factors. Therefore, some forensic evaluators extrapolate, adjust, or override recidivism rates derived from actuarial scales to predict the lifetime risk of committed offenses that accounts for external risk factors, those not addressed by the actuarial scales. However, critics contend that altering rates from actuarial scales degrades their predictive validity. This article makes the case for extrapolating risk for time of exposure and for evidence-based external risk factors. It proposes using odds ratios (ORs) from case-control studies to adjust predictions from follow-up cohort studies. Finally, it shows how evaluators can apply ORs and their margins of error to sex offender risk assessment.
We analyze viewers' experiences and understandings of an installation of portraits featuring vendors who sell Seattle’s Real Change street newspaper. In doing so, we argue that Real Change is ...enacting a complex politics of refusal and explore this in relation to future political lives of Real Change activism. We explore political possibilities for the transformation of urban life opened by the politics the exhibit expresses. We analyze the exhibit goals, representational strategies and viewer responses, exploring the complex politics Real Change is enacting to ensure vendor survival and anti-poverty activism. We argue that the white liberal visual regime (WLVR) ensures continued comfort of white privileged viewers, guaranteeing that their normatively white liberal understanding of impoverishment remains relatively untroubled. We explore disruptions of cultural norms that were possible within the WLVR as well as the limits of these disruptions. Drawing on critical race scholars we theorize visual fields as racially saturated, bolstering white comfort and white supremacy. While our argument begins from an art exhibit, it extends far beyond the politics of art. We analyze viewers’ responses to pose questions about whether/how these visual politics open pathways toward more profound re-learning of racialized relations that produce propertied personhood, racialized dispossession and premature death.
Cylindrospermopsin (CYN) is a naturally occurring alkaloid produced by a variety of cyanobacteria and known to induce oxidative stress-mediated toxicity in eukaryotic cells. Despite extensive ...research on the mechanism of CYN toxicity, an understanding of the structural features responsible for this toxicity and the mechanism by which it can enter the cell are still not clear. It was established that the presence of both the uracil and guanidine groups is essential in biological activity of CYN whilst not much is known in this regard on the role of tether that separates them and the attached hydroxyl group. Therefore, in the present study we have prepared three synthetic analogues possessing uracil and guanidine groups separated by a variable length tether (4–6 carbons) and containing a hydroxyl function in a position orientation to CYN, together with a tetracyclic analogue of CYN lacking the hydroxyl group at C-7. The toxicity of these compounds was then compared with CYN and guanidinoacetate (GAA; the primary substrate in CYN biosynthesis) in an in vitro model using human neutrophils isolated from healthy subjects. The lowest activity measured by means of reactive oxygen species generation, lipid peroxidation and cell death was observed for GAA and the tetracyclic analogue. The greatest toxicity was found in an analogue with a 6-carbon tether, but all three analogues and CYN caused rapid onset of redox imbalance. These results add to the general understanding of CYN toxicity and preliminary findings suggest that the –OH group at C-7 may be significant for the cellular transport of CYN and/or be involved in its toxic activity inside the cell, a hypothesis which requires further testing.
Analogues 11a–c of the alkaloid cylindrospermopsin 1, containing the key guanidine, hydroxyl and uracil motifs, have shown comparable cytotoxic activity to the natural material. Display omitted
•The role of the C7-OH group in the activity of cylindrospermopsin 1 is unknown.•Synthetic analogues (11a–c) of cylindrospermopsin 1 were prepared.•Toxicity of these analogues was compared with 1 using human neutrophils in vitro.•The greatest toxicity was found in 11c with a 6-carbon tether and an –OH group.•An analogue closely resembling 1 but lacking the C7-OH group had low toxicity.
Risk is the probability of an adverse event or outcome. In a previous article, I compared the Bayesian and Frequentist models of defining probability. This article compares the Bayesian and ...regression models of quantifying probability. Both approaches are widely used in the biomedical and behavioral sciences even though they yield different results. No consensus has emerged as to which is more appropriate. The choice between them remains controversial. This article concludes that the Bayesian model provides a viable alternative to logistic regression and may be more useful in quantifying the absolute recidivism risk of individual sex offenders. It shows how evaluators can easily calculate Bayesian probabilities and their associated credible intervals from an actuarial data set. Last, the article proposes a forensic practice guideline that evaluators do not conclude that an offender meets an absolute risk threshold unless the subject’s risk exceeds the threshold by a credible margin of error.
Pain and stress in crustaceans? Elwood, Robert W.; Barr, Stuart; Patterson, Lynsey
Applied animal behaviour science,
05/2009, Letnik:
118, Številka:
3
Journal Article
Recenzirano
We consider evidence that crustaceans might experience pain and stress in ways that are analogous to those of vertebrates. Various criteria are applied that might indicate a potential for pain ...experience: (1) a suitable central nervous system and receptors, (2) avoidance learning, (3) protective motor reactions that might include reduced use of the affected area, limping, rubbing, holding or autotomy, (4) physiological changes, (5) trade-offs between stimulus avoidance and other motivational requirements, (6) opioid receptors and evidence of reduced pain experience if treated with local anaesthetics or analgesics, and (7) high cognitive ability and sentience. For stress, we examine hormonal responses that have similar function to glucocorticoids in vertebrates. We conclude that there is considerable similarity of function, although different systems are used, and thus there might be a similar experience in terms of suffering. The treatment of these animals in the food industry and elsewhere might thus pose welfare problems.
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