Analysis of Germline Variants in CDH1, IGFBP3, MMP1, MMP3, STK15 and VEGF in Familial and Sporadic Renal Cell Carcinoma

BACKGROUND:The investigation of rare familial forms of kidney cancer has provided important insights into the biology of sporadic renal cell carcinoma (RCC). In particular, the identification of the von Hippel Lindau (VHL) familial cancer syndrome gene (VHL) provided the basis for the discovery that VHL is somatically inactivated in most sporadic clear cell RCC. Many cases of familial RCC do not have mutations in known RCC susceptibility genes and there is evidence that genetic modifiers may influence the risk of RCC in VHL disease patients. Hence we hypothesised that low-penetrance functional genetic variants in pathways related to the VHL protein (pVHL) function might (a) modify the phenotypic expression of VHL disease and/or (b) predispose to sporadic RCC. METHODOLOGY/PRINCIPAL FINDINGS:We tested this hypothesis for functional polymorphisms in CDH1 (rs16260), IGFBP3 (rs2854744), MMP1 (rs1799750), MMP3 (rs679620), STK15 (rs2273535) and VEGF (rs1570360). We observed that variants of MMP1 and MMP3 were significant modifiers of RCC risk (and risks of retinal angioma and cerebellar haemangioblastoma) in VHL disease patients. In addition, higher frequencies of the MMP1 rs1799750 2G allele (p = 0.017, OR 1.49, 95%CI 1.06-2.08) and the MMP1/MMP3 rs1799750/rs679620 2G/G haplotype (OR 1.45, 95%CI 1.01-2.10) were detected in sporadic RCC patients than in controls (n = 295). CONCLUSIONS/SIGNIFICANCE:These findings (a) represent the first example of genetic modifiers of RCC risk in VHL disease, (b) replicate a previous report of an association between MMP1/MMP3 variants and sporadic RCC and (c) further implicate MMP1/MMP3-related pathways in the pathogenesis of familial and sporadic RCC

Task-Based MoE for Multitask Multilingual Machine Translation

Mixture-of-experts (MoE) architecture has been proven a powerful method for diverse tasks in training deep models in many applications. However, current MoE implementations are task agnostic, treating all tokens from different tasks in the same manner. In this work, we instead design a novel method that incorporates task information into MoE models at different granular levels with shared dynamic task-based adapters. Our experiments and analysis show the advantages of our approaches over the dense and canonical MoE models on multi-task multilingual machine translations. With task-specific adapters, our models can additionally generalize to new tasks efficiently

The control of the drugstore beetle, Stegobium paniceum (Coleoptera: Anobiidae) with high and low temperatures

Botanicals; dried plants, roots, stems, leaves, seeds and flowers, have been used from the dawn of history as drugs or spices (Craker, 2007). Botanicals have been used in the health care system to improve blood circulation, reduce chronic fever and cure chronic constipation (Golob et al., 1999; Samy et al., 2008). The drugstore beetle, Stegobium paniceum (L.) (Coleoptera: Anobiidae), is a pest of stored medicinal and aromatic plants and one of the most common insects found in botanical warehouses (Abdelghany et al., 2010). Generally, mortality of each stage increased with an increase of temperature and exposure time. Heat tolerance for different stages from highest to lowest was; young larvae, old larvae, eggs, adult and pupae. The mortality after 7 h, at 42ºC for young larvae, old larvae, eggs, adult and pupae respectively was; 16 ± 5, 31 ± 6, 48 ± 3, 63 ± 8 and 86 ± 2% (mean + SEM). Similarly, the lethal time for 90% mortality (LT>sub>90) at 42ºC was; too low to estimate, 773, 144, 12 and 11 h. The LT90 value for young larvae at 42, 45, 50, 55 and 60ºC was 25, 20, 3.9, 0.18 and 0.08 h respectively. The cold tolerance of different stages at 0ºC from highest to lowest was adult, old larva, young larva, pupa, and egg. The LT90 at 0ºC was 298, 153, 151, 89 and 53 h, respectively. The LT90 value for adults at 5, -5, -10 and -15ºC was 792, 58, 2 and 0.8 h, respectively. The supercooling point of adults, young larvae, old larvae and pupae was -15.2 ± 2ºC, -9.0 ± 0.8ºC, -6.5 ± 0.5ºC, and -4.0 ± 1.4ºC respectively. Heat treatments that control young larvae should control all other stages of S. paniceum. Cold treatments that control adults should control all other stages of S. paniceum. Dried plants stored at 5ºC for 45 days or 42ºC for 30 h and then kept below 18ºC throughout the rest of the year, should remain pest-free without any chemical control. The full paper was submitted to Entomologia Experimentalis et Applicata. Keywords: Anobiidae, Heat, Cold, Supercooling point, Tolerance, Storage, Warehous

Relationship of depression, disability, and family caregiver attitudes to the quality of life of Kuwaiti persons with multiple sclerosis: a controlled study

<p>Abstract</p> <p>Background</p> <p>Assessment of subjective quality of life (QOL) of persons with multiple sclerosis (MS) could facilitate the detection of psychosocial aspects of disease that may otherwise go unrecognized. The objectives of the study were to (i) compare the QOL ratings of relapsing remitting (RRMS) and progressive (PMS) types of MS with those of a general population group and the impression of their family caregivers; and (ii) assess the association of demographic, clinical, treatment, depression, and caregiver variables with patients' QOL.</p> <p>Methods</p> <p>Consecutive clinic attendees at the national neurology hospital were assessed with the 26 -item WHOQOL Instrument, Beck's Depression Inventory and Expanded Disability Scale. Caregivers rated their impression of patients' QOL and attitudes to patients' illness.</p> <p>Results</p> <p>The 170 patients (60 m, 109 f) consisted of 145(85.3%) with RRMS and 25 with PMS, aged 32.4(SD 8.8), age at onset 27.1(7.7), EDSS score 2.9 (1.8), and 76% were employed. The patients were predominantly dissatisfied with their life circumstances. The RRMS group had higher QOL domain scores (P < 0.001), and lower depression(P > 0.05) and disability (P < 0.0001) scores than the PMS group. Patients had significantly lower QOL scores than the control group (P < 0.001). Caregiver impression was significantly correlated with patients' ratings. Depression was the commonest significant covariate of QOL domains. When we controlled for depression and disability scores, differences between the two MS groups became significant for only one (out of 6) QOL domains. Patients who were younger, better educated, employed, felt less sick and with lesser side effects, had higher QOL. The predictors of patients' overall QOL were disability score, caregiver impression of patients' QOL, and caregiver fear of having MS.</p> <p>Conclusion</p> <p>Our data indicate that MS patients in stable condition and with social support can hope to have better QOL, if clinicians pay attention to depression, disability, the impact of side effects of treatment and family caregiver anxieties about the illness. The findings call for a regular program of psychosocial intervention in the clinical setting, to address these issues and provide caregiver education and supports, in order to enhance the quality of care.</p

Contributions of point defects, chemical disorder, and thermal vibrations to electronic properties of Cd1-xZnxTe alloys

We present a first-principles study based on density functional theory of thermodynamic and electronic properties of the most important intrinsic defects in the semiconductor alloy Cd1-xZnxTe with x < 0.13. The alloy is represented by a set of supercells with disorder on the Cd/Zn sublattice. Defect formation energies as well as electronic and optical transition levels are analyzed as a function of composition. We show that defect formation energies increase with Zn content with the exception of the neutral Te vacancy. This behavior is qualitatively similar to but quantitatively rather different from the effect of volumetric strain on defect properties in pure CdTe. Finally, the relative carrier scattering strengths of point defects, alloy disorder, and phonons are obtained. It is demonstrated that for realistic defect concentrations, carrier mobilities are limited by phonon scattering for temperatures above approximately 150 K

Radial Velocity Studies of Close Binary Stars. XI

Radial-velocity measurements and sine-curve fits to the orbital radial velocity variations are presented for ten close binary systems: DU Boo, ET Boo, TX Cnc, V1073 Cyg, HL Dra, AK Her, VW LMi, V566 Oph, TV UMi and AG Vir. By this contribution, the DDO program has reached the point of 100 published radial velocity orbits. The radial velocities have been determined using an improved fitting technique which uses rotational profiles to approximate individual peaks in broadening functions. Three systems, ET Boo, VW LMi and TV UMi, were found to be quadruple while AG Vir appears to be a spectroscopic triple. ET Boo, a member of a close visual binary with $P_{vis} = 113$ years, was previously known to be a multiple system, but we show that the second component is actually a close, non-eclipsing binary. The new observations enabled us to determine the spectroscopic orbits of the companion, non-eclipsing pairs in ET Boo and VW LMi. The particularly interesting case is VW LMi, where the period of the mutual revolution of the two spectroscopic binaries is only 355 days. While most of the studied eclipsing pairs are contact binaries, ET Boo is composed of two double-lined detached binaries and HL Dra is single-lined detached or semi-detached system. Five systems of this group were observed spectroscopically before: TX Cnc, V1073 Cyg, AK Her (as a single-lined binary), V566 Oph, AG Vir, but our new data are of much higher quality than the previous studies.Comment: Accepted by AJ, August 2006, 10 figures, 3 table

Factors associated with quality of life of outpatients with breast cancer and gynecologic cancers and their family caregivers: a controlled study

<p>Abstract</p> <p>Background</p> <p>Quality of life (QOL) issues are of interest in cancer because effective methods of treatment and detection have led to an increase in the number of long-term survivors. The objectives of the study were: to assess the subjective QOL of stable Sudanese women cancer outpatients and their family caregivers, using the WHO 26-item QOL Instrument; compare with matched general population groups, as well as diabetic and psychiatric patient groups; examine patient-caregiver concordance in ratings; and assess the variables associated with their QOL, with a view to identifying factors that can enhance quality of care.</p> <p>Methods</p> <p>Responses of oncology outpatients with breast cancer (117), cervical cancer (46) and ovarian cancer (18) (aged 44.6, SD 11.5) were compared with those of their family caregivers and matched general population groups. Data were analyzed by univariate and multivariate statistics.</p> <p>Results</p> <p>The cancer groups had similar QOL domain scores, which were significantly lower than those of their caregivers, but higher than the control group as well as those of psychiatric and diabetic patients studied previously. Patients who were married, with higher education, better employment, and with longer duration of illness had higher QOL. Patients on radiotherapy and their caregivers had higher QOL scores. Correlations between patient's ratings and caregiver impression of patient's QOL were high. Caregiver impression was a significant predictor of patient's and caregiver's QOL. Other predictors for the patient were: currently feeling sick and duration of illness; for the caregiver: feeling sick, relationship to patient, and age.</p> <p>Conclusion</p> <p>Cancer patients in stable condition and with psychosocial support can hope to enjoy good QOL with treatment. The findings constitute an evidence base for the country's cancer care program, to boost national health education about prognosis in cancer. Families living with women cancer patients are vulnerable and need support if the patient is recently diagnosed, less educated, single, not formally employed; and the caregiver is female, parent, younger, less educated, unemployed and feels sick. Clinicians need to invest in the education and support of family caregivers. The patient-caregiver dyad should be regarded as a unit for treatment in cancer care.</p