Development of therapeutics for treatment of Ebola virus infection

Ebola virus infection can cause Ebola virus disease (EVD). Patients usually show severe symptoms, and the fatality rate can reach up to 90%. No licensed medicine is available. In this review, development of therapeutics for treatment of Ebola virus infection and EVD will be discussed.     

Potential pitfalls of the PTV concept in dose-to-medium planning optimization

In typical treatment planning of 3D IMRT, the incident energy fluence is optimized to achieve a homogeneous dose distribution to the PTV. The PTV includes the tumour but also healthy tissues that may have a different dose response for the same incident energy fluence, like bony structures included in the PTV (mandibles in head and neck tumours or femoral bones in sarcomas). Dose to medium optimization compensates for this heterogeneous response, leading to a non-homogeneous energy fluence in the PTV and a non-homogeneous dose in the CTV in the presence of geometric errors. We illustrate qualitatively this statement in a cylindrical geometry where the PTV includes a CTV (7 cm diameter) made of water surrounded by ICRU compact bone (1.2 cm thickness); such configuration was chosen to exaggerate the aforementioned effect. Optimization was performed assuming dose equals photon energy fluence times mass energy absorption coefficient. Bone has a 4% lower dose response in a 6 MV flattening filter free spectrum. After optimization either in medium or assuming everything as water composition, the geometry was shifted by 1.2 cm and dose recomputed. As expected, compensating for the under-response of the bone material during optimization in medium leads to an overdosage of the CTV when patient geometric errors are taken into account. Optimization in dose assuming everything as water composition leads to a uniform coverage. Robust optimization or forcing a uniform atomic composition in the PTV margin may resolve this incompatibility between the PTV concept and dose to medium optimization.     

Assessing the Effect of the Best Treatment. A Non-parametric Inference Problem

For patients of a certain type, a number of treatments are available. The effect of each such treatment is assumed to be described by a shift model; it is, however, admitted that there may be an interaction between patient and treatment, meaning in particular that the treatment which is best for one patient is not necessarily best for another. The problem is the following: if each patient is given the treatment which is optimal for that particular patient, will this produce a significant effect and, if so, how large is the effect?     

Comparative chlorine and temperature tolerance of the oyster crassostrea madrasensis: Implications for cooling system fouling

Crassostrea madrasensis is an important fouling oyster in tropical industrial cooling water systems. C. madrasensis individuals attach to surfaces by cementing one of their two valves to the substratum. Therefore, oyster fouling creates more problems than mussel fouling in the cooling conduits of power stations, because unlike the latter, the shell of the former remains attached to the substratum even after the death of the animal. However, there are no published reports on the tolerance of this species to chlorination and heat treatment. The mortality pattern and physiological behaviour (oxygen consumption and filtration rate) of three size groups (13 mm, 44 mm and 64 mm mean shell length) of C. madrasensis were studied at different residual chlorine concentrations (0.25, 0.5, 0.75, 1, 2, 3 to 5 mg l^{m 1}) and temperatures (30°C to 45°C). The effect of shell size (=age) on C. madrasensis mortality in the presence of chlorine and taking into account temperature was significant, with the largest size group oysters showing highest resistance. At 1 mg l^{m 1} residual chlorine, the 13 mm and 64 mm size group oysters took 504 h (21 d) and 744 h (31 d), respectively to reach 100% mortality. At 39°C, the 13 mm size group oysters took 218 min to reach 100% mortality, whereas the 64 mm size group oysters took 325 min. The oxygen consumption and filtration rate of C. madrasensis showed progressive reduction with increasing residual chlorine concentrations. However, the filtration rate and oxygen consumption responses of C. madrasensis were not significantly different between 30°C (control) and 37.5°C. There was a sharp decrease in the filtration rate and oxygen consumption at 38.5°C. A comparison of the present mortality data with previous reports on other bivalves suggests that the chlorine tolerance of C. madrasensis lies in between that of Perna viridis and Perna perna, while its temperature tolerance is significantly higher than that of the other two bivalve species. However, in power station heat exchangers, where simultaneous chlorine and thermal stresses are existent, C. madrasensis may have an edge over other common foulants, because of its high temperature tolerance.     

Comparison of dose distribution in IMRT and RapidArc technique in prostate radiotherapy

AimThe aim was to provide a dosimetric comparison between IMRT and RapidArc treatment plans with RPI index with simultaneous comparison of the treatment delivery time.BackgroundIMRT and RapidArc provide highly conformal dose distribution with good sparing of normal tissues. However, a complex spatial dosimetry of IMRT and RapidArc plans hampers the evaluation and comparison between plans calculated for the two modalities. RPI was used in this paper for treatment plan comparisons. The duration of the therapeutic session in RapidArc is reported to be shorter in comparison to therapeutic time of the other dynamic techniques. For this reasons, total treatment delivery time in both techniques was compared and discussed.Materials and methods15 patients with prostate carcinoma were randomly selected for the analysis. Two competitive treatment plans using respectively the IMRT and RapidArc techniques were computed for each patient in Eclipse planning system v. 8.6.15. RPIwin^® application was used for RPI calculations for each treatment plan.Additionally, total treatment time was compared between IMRT and RapidArc plans. Total treatment time was a sum of monitor units (MU) for each treated field.ResultsThe mean values of the RPI indices were insignificantly higher for IMRT plans in comparison to rotational therapy. Comparison of the mean numbers of monitor units confirmed that the use of rotational technique instead of conventional static field IMRT can significantly reduce the treatment time.ConclusionAnalysis presented in this paper, demonstrated that RapidArc can compete with the IMRT technique in the field of treatment plan dosimetry reducing the time required for dose delivery.     

Evaluation of past and potential phosphorus uptake at the Orlando Easterly Wetland

The Orlando Easterly Wetland (OEW), located near Christmas, Florida, USA, is among the longer-lived treatment wetlands in the United States. It was established in the late 1980s to reduce nitrogen and phosphorus concentrations from tertiary treated wastewater bound for the St. Johns River. A goal of 0.07 mg/l total phosphorus concentration has been set by the regulating agency (St. Johns River Water Management District). In order to understand and define the operating conditions for which this target could be met, a systematic study of historic phosphorus uptake was performed using a traditional first-order model. Phosphorus uptake performance is shown to correlate well with hydraulic performance for two parallel upstream cells. The first-order model is enhanced with predictive capabilities that acknowledge the correlation between the phosphorus uptake rate constant and the hydraulic loading rate observed in the system. Inherent limitations with the first-order modeling approach are addressed and uncertainty in model performance is used to bound predictions.     

The effectiveness of constructed wetland for treatment of woodwaste leachate

Percolation of rainfall through woodwaste piles leaches natural chemicals from the wood residuals that can have adverse impacts on the environment. A study was conducted on a woodwaste storage site, adjacent to the Lower Fraser River, near Mission, BC, Canada. The objective of this research was to evaluate the effectiveness of constructed wetland for treatment of this woodwaste leachate. The leachate was characterized by high oxygen demand, tannin and lignin, and volatile fatty acids (VFAs), but low pH and nutrients. Diluted leachate passed through six pilot-scale wetland cells, four planted with cattail (Typha latifolia) and two unplanted controls, with a hydraulic retention time of 7 days and an average depth of 40 cm. Nutrient addition and pH adjustments were made to improve contaminant removal. Reductions in contaminants were consistently achieved, with average removals for BOD, COD, VFAs and tannin and lignin of 60, 50, 69 and 42%, respectively. Climatic conditions had an impact on the performance of the constructed wetland. Further operation of the system will help to elucidate the seasonal fluctuations. Aging of the constructed wetland system increased the treatment performance.     

肺部感染对支气管封堵治疗影响的实验研究

目的:探讨肺部感染对支气管封堵治疗影响的动物实验性研究。方法:取健康杂种犬18条,分为3组(A、B、C组)(n=6),经支气管镜每只犬置入致密螺栓状支气管封堵器2枚,其中A、B组为肺部感染组,C组仅为单纯封堵(A、C组封堵后使用抗生素,而B组封堵后未使用抗生素)。观察实验动物的耐受性,定期复查血象、支气管镜、胸部CT扫描,8周后观察封堵器附近支气管组织及远端肺组织变化。结果:观察期内,除1例因给药管不慎封堵入靶支气管内而死亡外,其余犬耐受性良好;截至封堵第8周,36只封堵器中,脱落共有0只(0/36)。胸部CT扫描和组织病理学检查证实,部分封堵的肺叶有萎陷,封堵部位远端肺泡腔缩小,5例封堵部位及其周围有轻度阻塞性炎症改变,未出现肺脓肿及坏死。肺部感染因素对犬的恢复有延迟;而感染组术后肌注抗生素与否,并未能缩短实验动物的不适反应过程,亦未能预防或减少阻塞性炎症的发生。结论:试制的支气管封堵器置入方便,组织相容性好;无论单纯封堵还是肺部感染组的封堵,各组实验动物均有较好的耐受性,但是肺部感染因素对犬的恢复有延迟;肺部感染组术后肌注抗生素与否,对提高动物的耐受程度无明显作用。     

桡动脉-头静脉瘘成熟障碍原因分析及治疗的研究进展

桡动脉-头静脉瘘因其通畅率高、并发症少而被认为是血液透析血管通路的第一选择,但高达50%的内瘘因各种原因不能成熟,这主要是由于持续性地低血流量或穿刺困难导致无法进行充分的血液透析。常见的原因有流入道或流出道狭窄、吻合口狭窄、静脉位置过深及分支静脉的分流。此外,血栓形成是造成狭窄的一个常见原因。术前通过体格检查和超声检查评估血管条件选择合适的血管对于内瘘的成熟有着重要的意义。应针对引起成熟障碍的病因选择合适的治疗方法:术后普遍应用阿司匹林预防血栓形成进而减少狭窄的发生;外科手术有绕过损伤区域的优点但却创造一个新的吻合;近年来血管腔内技术因其微创的特点在大多数时候是第一选择。本文将对内瘘成熟障碍的定义、病因、诊断及治疗进行综述。