Global Sensitivity Analysis for Randomized Trials with Informative Assessment Times: A Fully Parametric Approach

Many randomized trials are designed to collect outcomes at fixed points in times after randomized. In practice, study participants miss their assessments or are assessed off-schedule. If and when individuals are assessed may be informative. In this thesis, we develop a sensitivity analysis methodology for analyzing randomized trials with a potentially informative assessment process. We develop these methods in the context of the Asthma Research for the Community (ARC) trial

A Novel Buffer Tank to Attenuate the Peak Flow of Runoff

Impermeable pavements and roofs in urban areas convert most rainfall to runoff, which is commonly discharged to local sewers pipes and finally to the nearby streams and rivers. In case of heavy rain, the peak flow of runoff usually exceeds the carrying capacity of the local sewer pipes, leading to urban flooding. Traditional facilities, such as green roofs, permeable pavements, soakaways, rainwater tanks, rain barrels, and others reduce the runoff volume in case of a small rain but fail in case of a heavy rain. Here we propose a novel rainwater buffer tank to detain runoff from the nearby sealed surfaces in case of heavy rain and then to discharge rainwater from an orifice at the tank’s bottom. We found that considering a 100m2 rooftop with 0.80 runoff coefficient and a 10cm rainfall depth for an hour, a cubic tank with internal edge side of a square of 2 m attenuates the peak flow about 45%. To reduce a desirable peak flow, the outlet orifice of the buffer tank must be optimized according to site-specific conditions. The orifice can be set at an elevation from the tank’s bottom to create a dead storage for harvesting rainwater

Protein Tyrosine Kinase 6 Protects Cells from Anoikis by Directly Phosphorylating Focal Adhesion Kinase and Activating AKT

Protein tyrosine kinase 6 (PTK6) is a non-receptor tyrosine kinase expressed in epithelial cancers. Disruption of Ptk6 decreases AOM-induced colon tumorigenesis in mice by preventing STAT3 activation. Relocalization of PTK6 in prostate cancers contributes to increased growth. Although not expressed in normal breast or ovary, PTK6 promotes anchorage-independent survival of breast and ovarian tumor cells. We identified several potential PTK6 substrates in the human SW620 colon cancer cell line using mass spectrometry, including FAK (focal adhesion kinase). We show that FAK is a direct substrate of PTK6 in vitro and in vivo. Expression of membrane targeted active PTK6 (Palm-PTK6-YF) induces constitutive activation of FAK and cell morphology changes, which are independent of SRC family kinases in Src−/−, Yes−/−, Fyn−/− (SYF) mouse embryonic fibroblasts (MEFs). Palm-PTK6-YF expressing SYF cells are transformed and overcome contact inhibition, form colonies in transformation assays, proliferate in suspension, and form tumors in a xenograft model. Expression of FAK and Palm-PTK6-YF in Fak−/− MEFs synergistically activates AKT and protects cells against anoikis. However, expression of Palm-PTK6-YF in Akt1/2−/− MEFs fails to protect cells from anoikis, indicating AKT is critical in PTK6 and FAK mediated survival signaling. In a conditional Pten knockout murine prostate cancer model, we identify prostate epithelial cells with enhanced activation of endogenous PTK6 and FAK at the plasma membrane. Knockdown of PTK6 in the PC3 human prostate cancer cell line disrupts FAK and AKT activation and promotes anoikis, which can be rescued by exogenous expression of FAK. Our data reveal important roles for a PTK6-FAK-AKT signaling axis in promoting anchorage-independent cell survival

Association of interleukin 17 / angiotensin II with refractory hypertension risk in hemodialysis patients.

Objective: The study was performed to investigate the association of interleukin 17 (IL 17) or angiotensin II (Ang II) with refractory hypertension risk in hemodialysis patients. Methods: Ninety hemodialysis patients were enrolled into this study, and those with hypertension were divided into two groups. The Easy-to-Control Hypertension group (ECHG) had fifty patients, while the refractory hypertension group (RHG) had forty patients. Twenty healthy individuals were recruited as the control group. IL17 and Ang II were determined using a human IL 17 / Ang II enzyme-linked immunosorbent assay kit. Serum IL 17 and Ang II concentrations in RHG patients were higher than those in ECHG patients. Results: Serum IL 17 and Ang II concentrations in both patient groups were higher than those in the control group. Linear regression analysis showed a positive correlation between IL 17 and Ang II. In multivariate regression analysis, we found that IL17 and Ang II were associated with refractory hypertension risk in hemodialysis patients. Conclusion: IL17 and Ang II were associated with refractory hypertension risk in hemodialysis patients. There was also a positive correlation between IL 17and Ang II

Layered Rendering Diffusion Model for Zero-Shot Guided Image Synthesis

This paper introduces innovative solutions to enhance spatial controllability in diffusion models reliant on text queries. We present two key innovations: Vision Guidance and the Layered Rendering Diffusion (LRDiff) framework. Vision Guidance, a spatial layout condition, acts as a clue in the perturbed distribution, greatly narrowing down the search space, to focus on the image sampling process adhering to the spatial layout condition. The LRDiff framework constructs an image-rendering process with multiple layers, each of which applies the vision guidance to instructively estimate the denoising direction for a single object. Such a layered rendering strategy effectively prevents issues like unintended conceptual blending or mismatches, while allowing for more coherent and contextually accurate image synthesis. The proposed method provides a more efficient and accurate means of synthesising images that align with specific spatial and contextual requirements. We demonstrate through our experiments that our method provides better results than existing techniques both quantitatively and qualitatively. We apply our method to three practical applications: bounding box-to-image, semantic mask-to-image and image editing

Whole-genome resequencing reveals signatures of selection and timing of duck domestication

BackgroundThe genetic basis of animal domestication remains poorly understood, and systems with substantial phenotypic differences between wild and domestic populations are useful for elucidating the genetic basis of adaptation to new environments as well as the genetic basis of rapid phenotypic change. Here, we sequenced the whole genome of 78 individual ducks, from two wild and seven domesticated populations, with an average sequencing depth of 6.42X per individual.ResultsOur population and demographic analyses indicate a complex history of domestication, with early selection for separate meat and egg lineages. Genomic comparison of wild to domesticated populations suggests that genes that affect brain and neuronal development have undergone strong positive selection during domestication. Our FST analysis also indicates that the duck white plumage is the result of selection at the melanogenesis-associated transcription factor locus.ConclusionsOur results advance the understanding of animal domestication and selection for complex phenotypic traits

The First Case of Ischemia-Free Kidney Transplantation in Humans

Background: Ischemia-reperfusion injury (IRI) has been considered an inevitable event in organ transplantation since the first successful kidney transplant was performed in 1954. To avoid IRI, we have established a novel procedure called ischemia-free organ transplantation. Here, we describe the first case of ischemia-free kidney transplantation (IFKT). Materials and Methods: The kidney graft was donated by a 19-year-old brain-dead donor. The recipient was a 47-year-old man with end-stage diabetic nephropathy. The graft was procured, preserved, and implanted without cessation of blood supply using normothermic machine perfusion. Results: The graft appearance, perfusion flow, and urine production suggested that the kidney was functioning well-during the whole procedure. The creatinine dropped rapidly to normal range within 3 days post-transplantation. The levels of serum renal injury markers were low post-transplantation. No rejection or vascular or infectious complications occurred. The patient had an uneventful recovery. Conclusion: This paper marks the first case of IFKT in humans. This innovation may offer a unique solution to optimizing transplant outcomes in kidney transplantation

The influence of PC6 on cardiovascular disorders: a review of central neural mechanisms

PC6 is a classic acupuncture point in traditional Chinese medicine. It is considered to be effective when treating cardiovascular disorders. In the present review the authors have focused on the neurophysiological bases of the effects of PC6 stimulation on cardiovascular mechanisms. Experimental studies have shown that the hypothalamic rostral ventrolateral medulla, arcuate nucleus and ventrolateral periaqueductal gray are involved in acupuncture attenuation of sympathoexcitatory cardiovascular reflex responses. This long-loop pathway also appears to contribute to the long-lasting, acupuncture-mediated attenuation of sympathetic premotor outflow and excitatory cardiovascular reflex responses. Acupuncture of PC6 modulates the activity in the cardiovascular system, an effect that may be attributed to attenuation of sympathoexcitatory cardiovascular reflex responses