changes in aqueductal csf stroke volume and progression of symptoms in patients with unshunted idiopathic normal pressure hydrocephalus

BACKGROUND AND PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) represents a diagnostic challenge, given its variable presentation and progression. Stroke volume (SV), defined as the mean volume of CSF passing through the aqueduct during both systole and diastole, greater than or equal to 42 μL, serves as a selection criterion for patients with good probabilities of improvement after ventriculoperitoneal shunt surgery (VPS). In this study, we evaluated the changes in SV during the progression of clinical symptoms in patients with suspected NPH. MATERIALS AND METHODS: Nine patients who presented with clinical and radiologic evidence of NPH, but refused treatment with VPS, were evaluated every 6 months for up to 2 years for progression in their clinical symptoms and changes in their SV, as measured by phase-contrast cine MR imaging (PCCMR). RESULTS: SV seems to increase between the onset of the symptoms and the following 18 to 20 months, then seems to plateau, followed in the next 18 to 20 months by a slight decline, and finally to a more precipitous drop in the next 12 months. During this time, however, the patient9s clinical symptoms progressively worsen. CONCLUSION: Patients with a low SV have not necessarily had brain atrophy and can show, in the following months, a progressive increase in SV, which qualifies them as good candidates for VPS. The progressive reduction of the SV in untreated patients with worsening clinical symptoms may be a sign of a progressive cerebral ischemic injury, which renders the NPH irreversible

Upper bounds for the eigenvalues of Hessian equations

We prove some upper bounds for the Dirichlet eigenvalues of a class of fully nonlinear elliptic equations, namely the Hessian equationsComment: 15 pages, 1 figur

Imaging biomarkers of adiposity and sarcopenia as potential predictors for overall survival among patients with endometrial cancer treated with bevacizumab

Objective:To examine associations of body mass index (BMI), subcutaneous fat area (SFA) and density (SFD), visceral fat area (VFA) and density (VFD) and total psoas area (TPA) to outcomes among patients receiving chemotherapy with or without bevacizumab for advanced or recurrent endometrial cancer (EC). Methods:This was a multi-institutional, retrospective study of patients with EC treated with and without bevacizumab as part of front-line, platinum based chemotherapy. Demographics and clinical characteristics were collected. SFA, VFA, SFD, VFD, and TPA were determined from pre-treatment CT scans using a deep learning algorithm. Data was compared with overall survival (OS) and progression free survival (PFS). Results:Seventy-eight patients were analyzed. The majority were Caucasian (87.2%) with a mean BMI of 34.7 kg/m2. PFS and OS did not differ between patients with BMI, SFA, VFA, SFD, VFD, or TPA ≥ the 50th percentile compared to <50th percentile (p = 0.91, 0.45, 0.71, 0.74, 0.60, and 0.74 respectively) and (p = 0.99, 0.59, 0.14, 0.77, and 0.85 respectively). When adjusting for prognostic factors, elevated VFA trended towards shorter OS (25.1 vs 59.5 months, HR = 1.68 [0.92-3.05]).Patients receiving bevacizumab had similar OS compared to those who did not (37.6 vs 44.5 months, p = 0.409). When stratified by adiposity markers, no subset demonstrated benefit from bevacizumab. Conclusion:Obesity has been associated with increased levels of vascular endothelial growth factor (VEGF), the main target for bevacizumab therapy. Imaging measurements of VFA may provide prognostic information for patients with EC but no adiposity marker was predictive of improved response to bevacizumab

Digital karyotyping reveals probable target genes at 7q21.3 locus in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is a worldwide malignant liver tumor with high incidence in China. Subchromosomal amplifications and deletions accounted for major genomic alterations occurred in HCC. Digital karyotyping was an effective method for analyzing genome-wide chromosomal aberrations at high resolution.</p> <p>Methods</p> <p>A digital karyotyping library of HCC was constructed and 454 Genome Sequencer FLX System (Roche) was applied in large scale sequencing of the library. Digital Karyotyping Data Viewer software was used to analyze genomic amplifications and deletions. Genomic amplifications of genes detected by digital karyotyping were examined by real-time quantitative PCR. The mRNA expression level of these genes in tumorous and paired nontumorous tissues was also detected by real-time quantitative RT-PCR.</p> <p>Results</p> <p>A total of 821,252 genomic tags were obtained from the digital karyotyping library of HCC, with 529,162 tags (64%) mapped to unique loci of human genome. Multiple subchromosomal amplifications and deletions were detected through analyzing the digital karyotyping data, among which the amplification of 7q21.3 drew our special attention. Validation of genes harbored within amplicons at 7q21.3 locus revealed that genomic amplification of SGCE, PEG10, DYNC1I1 and SLC25A13 occurred in 11 (21%), 11 (21%), 11 (21%) and 23 (44%) of the 52 HCC samples respectively. Furthermore, the mRNA expression level of SGCE, PEG10 and DYNC1I1 were significantly up-regulated in tumorous liver tissues compared with corresponding nontumorous counterparts.</p> <p>Conclusions</p> <p>Our results indicated that subchromosomal region of 7q21.3 was amplified in HCC, and SGCE, PEG10 and DYNC1I1 were probable protooncogenes located within the 7q21.3 locus.</p

Is age a prognostic biomarker for survival among women with locally advanced cervical cancer treated with chemoradiation? An NRG Oncology/Gynecologic Oncology Group ancillary data analysis

Objective To determine the effect of age on completion of and toxicities following treatment of local regionally advanced cervical cancer (LACC) on Gynecologic Oncology Group (GOG) Phase I–III trials. Methods An ancillary data analysis of GOG protocols 113, 120, 165, 219 data was performed. Wilcoxon, Pearson, and Kruskal-Wallis tests were used for univariate and multivariate analysis. Log rank tests were used to compare survival lengths. Results One-thousand-three-hundred-nineteen women were included; 60.7% were Caucasian, 15% were age 60–70 years and an additional 5% were >70; 87% had squamous histology, 55% had stage IIB disease and 34% had IIIB disease. Performance status declined with age (p = 0.006). Histology and tumor stage did not significantly differ., Number of cycles of chemotherapy received, radiation treatment time, nor dose modifications varied with age. Notably, radiation protocol deviations and failure to complete brachytherapy (BT) did increase with age (p = 0.022 and p 50 for all-cause mortality (HR 1.02; 95% CI, 1.01–1.04) was found, but no association between age and disease specific mortality was found. Conclusion This represents a large analysis of patients treated for LACC with chemo/radiation, approximately 20% of whom were >60 years of age. Older patients, had higher rates of incomplete brachytherapy which is not explained by collected toxicity data. Age did not adversely impact completion of chemotherapy and radiation or toxicities

The muscle protein dysferlin accumulates in the Alzheimer brain

Dysferlin is a transmembrane protein that is highly expressed in muscle. Dysferlin mutations cause limb-girdle dystrophy type 2B, Miyoshi myopathy and distal anterior compartment myopathy. Dysferlin has also been described in neural tissue. We studied dysferlin distribution in the brains of patients with Alzheimer disease (AD) and controls. Twelve brains, staged using the Clinical Dementia Rating were examined: 9 AD cases (mean age: 85.9 years and mean disease duration: 8.9 years), and 3 age-matched controls (mean age: 87.5 years). Dysferlin is a cytoplasmic protein in the pyramidal neurons of normal and AD brains. In addition, there were dysferlin-positive dystrophic neurites within Aβ plaques in the AD brain, distinct from tau-positive neurites. Western blots of total brain protein (RIPA) and sequential extraction buffers (high salt, high salt/Triton X-100, SDS and formic acid) of increasing protein extraction strength were performed to examine solubility state. In RIPA fractions, dysferlin was seen as 230–272 kDa bands in normal and AD brains. In serial extractions, there was a shift of dysferlin from soluble phase in high salt/Triton X-100 to the more insoluble SDS fraction in AD. Dysferlin is a new protein described in the AD brain that accumulates in association with neuritic plaques. In muscle, dysferlin plays a role in the repair of muscle membrane damage. The accumulation of dysferlin in the AD brain may be related to the inability of neurons to repair damage due to Aβ deposits accumulating in the AD brain

High serum levels of transforming growth factor β1 are associated with increased cortical thickness in cingulate and right frontal areas in healthy subjects

ABSTRACT

Workforce scheduling and routing problems: literature survey and computational study

In the context of workforce scheduling, there are many scenarios in which personnel must carry out tasks at different locations hence requiring some form of transportation. Examples of these type of scenarios include nurses visiting patients at home, technicians carrying out repairs at customers’ locations and security guards performing rounds at different premises, etc. We refer to these scenarios as workforce scheduling and routing problems (WSRP) as they usually involve the scheduling of personnel combined with some form of routing in order to ensure that employees arrive on time at the locations where tasks need to be performed. The first part of this paper presents a survey which attempts to identify the common features of WSRP scenarios and the solution methods applied when tackling these problems. The second part of the paper presents a study on the computational difficulty of solving these type of problems. For this, five data sets are gathered from the literature and some adaptations are made in order to incorporate the key features that our survey identifies as commonly arising in WSRP scenarios. The computational study provides an insight into the structure of the adapted test instances, an insight into the effect that problem features have when solving the instances using mathematical programming, and some benchmark computation times using the Gurobi solver running on a standard personal computer