Crude incidence in two-phase designs in the presence of competing risks.

BackgroundIn many studies, some information might not be available for the whole cohort, some covariates, or even the outcome, might be ascertained in selected subsamples. These studies are part of a broad category termed two-phase studies. Common examples include the nested case-control and the case-cohort designs. For two-phase studies, appropriate weighted survival estimates have been derived; however, no estimator of cumulative incidence accounting for competing events has been proposed. This is relevant in the presence of multiple types of events, where estimation of event type specific quantities are needed for evaluating outcome.MethodsWe develop a non parametric estimator of the cumulative incidence function of events accounting for possible competing events. It handles a general sampling design by weights derived from the sampling probabilities. The variance is derived from the influence function of the subdistribution hazard.ResultsThe proposed method shows good performance in simulations. It is applied to estimate the crude incidence of relapse in childhood acute lymphoblastic leukemia in groups defined by a genotype not available for everyone in a cohort of nearly 2000 patients, where death due to toxicity acted as a competing event. In a second example the aim was to estimate engagement in care of a cohort of HIV patients in resource limited setting, where for some patients the outcome itself was missing due to lost to follow-up. A sampling based approach was used to identify outcome in a subsample of lost patients and to obtain a valid estimate of connection to care.ConclusionsA valid estimator for cumulative incidence of events accounting for competing risks under a general sampling design from an infinite target population is derived

Separability and entanglement in 2x3xN composite quantum systems

The separability and entanglement of quantum mixed states in \Cb^2 \otimes \Cb^3 \otimes \Cb^N composite quantum systems are investigated. It is shown that all quantum states $\rho$ with positive partial transposes and rank $r(\rho)\leq N$ are separable.Comment: Latex, 15 page

Mechanisms of c-Myc Degradation by Nickel Compounds and Hypoxia

Nickel (Ni) compounds have been found to cause cancer in humans and animal models and to transform cells in culture. At least part of this effect is mediated by stabilization of hypoxia inducible factor (HIF1a) and activating its downstream signaling. Recent studies reported that hypoxia signaling might either antagonize or enhance c-myc activity depending on cell context. We investigated the effect of nickel on c-myc levels, and demonstrated that nickel, hypoxia, and other hypoxia mimetics degraded c-myc protein in a number of cancer cells (A549, MCF-7, MDA-453, and BT-474). The degradation of the c-Myc protein was mediated by the 26S proteosome. Interestingly, knockdown of both HIF-1α and HIF-2α attenuated c-Myc degradation induced by Nickel and hypoxia, suggesting the functional HIF-1α and HIF-2α was required for c-myc degradation. Further studies revealed two potential pathways mediated nickel and hypoxia induced c-myc degradation. Phosphorylation of c-myc at T58 was significantly increased in cells exposed to nickel or hypoxia, leading to increased ubiquitination through Fbw7 ubiquitin ligase. In addition, nickel and hypoxia exposure decreased USP28, a c-myc de-ubiquitinating enzyme, contributing to a higher steady state level of c-myc ubiquitination and promoting c-myc degradation. Furthermore, the reduction of USP28 protein by hypoxia signaling is due to both protein degradation and transcriptional repression. Nickel and hypoxia exposure significantly increased the levels of dimethylated H3 lysine 9 at the USP28 promoter and repressed its expression. Our study demonstrated that Nickel and hypoxia exposure increased c-myc T58 phosphorylation and decreased USP28 protein levels in cancer cells, which both lead to enhanced c-myc ubiquitination and proteasomal degradation

APOLO-Bari, an internet-based program for longitudinal support of bariatric surgery patients: study protocol for a randomized controlled trial

Background: Despite evidence of successful weight loss for bariatric surgery patients, some patients experience considerable weight regain over the long term. Given the strong association between post-surgery health behaviors and outcomes, aftercare intervention to address key behaviors appears to be a reasonable relapse-prevention strategy. As the burden of obesity rates increases in healthcare centers, an internet-based program appears to be a reasonable strategy for supporting bariatric surgery patients in the long term. The primary purpose of the current project is to develop and test the efficacy and perceived utility of APOLO-Bari.Methods/design: This study is a randomized control trial, which will be conducted in two hospital centers in the North of Portugal; it includes a control group receiving treatment as usual and an intervention group receiving the APOLO-Bari program for one year in addition to treatment as usual. A total of 180 male and female participants who underwent bariatric surgery (gastric sleeve or gastric bypass surgery) for 12 to 20 months will be recruited. Both groups will complete a similar set of questionnaires at baseline, every 4 months until the end of the intervention, and at 6 and 12 months follow-up. Assessment includes anthropometric variables and psychological self-report measures. The primary outcome measure will be weight regain measured at the end of treatment, and at 6 and 12 months follow-up. The secondary aims are to test the cost-effectiveness of the intervention and to investigate psychological predictors and trajectories of weight regain. APOLO-Bari was developed to address the weight regain problem in the bariatric population by offering additional guidance to bariatric patients during the postoperative period. The program includes: (a) a psychoeducational cognitive-behavioral-based self-help manual, (b) a weekly feedback messaging system that sends a feedback statement related to information reported by the participant, and (c) interactive chat sessions scheduled witThis research was partially supported by the Fundacao para a Ciencia e a Tecnologia through a European Union COMPETE program grant to Eva Conceicao (IF/01219/2014 and PTDC/MHC-PCL/4974/2012), a doctoral scholarship to Ana Pinto-Bastos (SFRH/BD/104159/2014), a doctoral scholarship to Sofia Ramalho (SFRH/BD/104182/2014), and a postdoctoral scholarship to Ana Rita Vaz (SFRH/BPD/94490/2013), co-financed by FEDER under the PT2020 Partnership Agreement (UID/PSI/01662/2013).info:eu-repo/semantics/publishedVersio

Elucidation of the Dual Role of Mycobacterial MoeZR in Molybdenum Cofactor Biosynthesis and Cysteine Biosynthesis

The pathway of molybdenum cofactor biosynthesis has been studied in detail by using proteins from Mycobacterium species, which contain several homologs associated with the first steps of Moco biosynthesis. While all Mycobacteria species contain a MoeZR, only some strains have acquired an additional homolog, MoeBR, by horizontal gene transfer. The role of MoeBR and MoeZR was studied in detail for the interaction with the two MoaD-homologs involved in Moco biosynthesis, MoaD1 and MoaD2, in addition to the CysO protein involved in cysteine biosynthesis. We show that both proteins have a role in Moco biosynthesis, while only MoeZR, but not MoeBR, has an additional role in cysteine biosynthesis. MoeZR and MoeBR were able to complement an E. coli moeB mutant strain, but only in conjunction with the Mycobacterial MoaD1 or MoaD2 proteins. Both proteins were able to sulfurate MoaD1 and MoaD2 in vivo, while only MoeZR additionally transferred the sulfur to CysO. Our in vivo studies show that Mycobacteria have acquired several homologs to maintain Moco biosynthesis. MoeZR has a dual role in Moco- and cysteine biosynthesis and is involved in the sulfuration of MoaD and CysO, whereas MoeBR only has a role in Moco biosynthesis, which is not an essential function for Mycobacteria

Biofunctionalization of zinc oxide nanowires for DNA sensory applications

We report on the biofunctionalization of zinc oxide nanowires for the attachment of DNA target molecules on the nanowire surface. With the organosilane glycidyloxypropyltrimethoxysilane acting as a bifunctional linker, amino-modified capture molecule oligonucleotides have been immobilized on the nanowire surface. The dye-marked DNA molecules were detected via fluorescence microscopy, and our results reveal a successful attachment of DNA capture molecules onto the nanowire surface. The electrical field effect induced by the negatively charged attached DNA molecules should be able to control the electrical properties of the nanowires and gives way to a ZnO nanowire-based biosensing device

Improving the sensitivity of the hop index in patients with an ACL deficient knee by transforming the hop distance scores

BACKGROUND: The one leg hop for distance is one of the most commonly employed functional tests utilized in the evaluation of the ACL deficient and reconstructed patient. While the reliability of the hop test scores has been well established, validity studies have revealed low sensitivity rates in detecting functional limitations using the hop index (the ratio or percentage of limb performance). However, the impact of the inherent limitations associated with the hop index have not been investigated to date. One specific limitation relates to the impact of the differences in the underlying hop distance scores. Therefore, this pilot study set out to determine: 1) the impact that between limb differences in hop distance has on the sensitivity of the hop index in detecting functional limitations and; 2) whether a logarithmic transformation of the underlying hop distance scores improves the sensitivity of the hop index. METHODS: A cross sectional design involving the evaluation of one leg hop for distance performance in a consecutive sample of 10 ACL deficient males with an isolated ACL tear awaiting reconstructive surgery and nine gender, age-matched controls. RESULTS: In the ACL deficient, the hop index was associated with the distance hopped on the non-injured limb (r = -0.66, p = 0.04) but not on the injured limb. Transformation (logarithmic) of the hop distance scores and re-calculation of the hop index using the transformed scores increased the sensitivity of the hop index in the detection of functional limitations from 20 to 60% and 50 to 70% using the normal limb symmetry reference norms of ≥ 85% and 90% respectively. CONCLUSION: The distance hopped on the non-injured limb is a critical factor in detecting functional limitations using the hop index in patients with an ACL deficient knee. Logarithmic transformation of the hop distance scores minimizes the effect of the arithmetic differences between limbs however; the sensitivity of the hop index in detecting abnormal limb symmetry remains low