Alterations of tumor suppressor gene p16(INK4a )in pancreatic ductal carcinoma

BACKGROUND: Cell cycle inhibitor and tumor suppressor gene p16 / MTS-1 has been reported to be altered in a variety of human tumors. The purpose of the study was to evaluate primary pancreatic ductal adenocarcinomas for potentially inactivating p16 alterations. METHODS: We investigated the status of p16 gene by polymerase chain reaction (PCR), nonradioisotopic single strand conformation polymorphism (SSCP), DNA sequencing and hypermethylation analysis in 25 primary resected ductal adenocarcinomas. In addition, we investigated p16 protein expression in these cases by immunohistochemistry (IHC) using a monoclonal antibody clone (MS-887-PO). RESULTS: Out of the 25 samples analyzed and compared to normal pancreatic control tissues, the overall frequency of p16 alterations was 80% (20/25). Aberrant promoter methylation was the most common mechanism of gene inactivation present in 52% (13/25) cases, followed by coding sequence mutations in 16% (4/25) cases and presumably homozygous deletion in 12% (3/25) cases. These genetic alterations correlated well with p16 protein expression as complete loss of p16 protein was found in 18 of 25 tumors (72%). CONCLUSION: These findings confirm that loss of p16 function could be involved in pancreatic cancer and may explain at least in part the aggressive behaviour of this tumor type

The health effects associated with physical, sexual and psychological gender-based violence against men and women:a Burden of Proof study

The health impacts of exposure to physical, sexual or psychological gender-based violence (GBV) against men and women are substantial yet not well delineated. We systematically reviewed and meta-analysed 40 studies to evaluate the associations between GBV (including but not limited to intimate partner violence) and eight health outcomes: sexually transmitted infections excluding HIV, maternal abortion and miscarriage, HIV/AIDS, major depressive disorder, anxiety disorders, drug use disorders, alcohol use disorders and self-harm. Using the Burden of Proof methods, we generated conservative metrics of association-including star ratings from one to five-reflecting both effect size and evidence strength. Sexual violence was associated with six outcomes, with moderate, three-star evidence of association for sexually transmitted infections, maternal abortion and miscarriage, and major depressive disorder-increasing the risk by at least 104%, 101% and 50%, respectively. Seven outcomes were associated with physical GBV with two- or one-star associations, reflecting weak associations and/or inconsistent evidence. Of the four health outcomes analysed in relation to psychological GBV, one, major depressive disorder, had a significant association with a one-star rating. These findings emphasize the serious health consequences of GBV for survivors and the necessity of additional data to further our understanding of this complex public health issue.</p

Health effects associated with exposure of children to physical violence, psychological violence and neglect:a Burden of Proof study

The health toll of child maltreatment or violence against children (VAC) has not yet been comprehensively evaluated. Here, in our systematic review and meta-analyses, we focused on the health impacts of physical violence, psychological violence and neglect during childhood. Utilizing the Burden of Proof methodology, which generates conservative measures of association while accounting for heterogeneity between input studies, we evaluated 35 associations between VAC and adverse health outcomes, identifying 27 statistically significant links. The associations between physical violence and major depressive disorder, ischaemic heart disease, alcohol use disorder, eating disorders and drug use disorders were rated as moderately weak, reflecting a small effect size and/or inconsistent evidence. The minimum increased risk ranged from 16% for depression to 2% for drug use disorders. Psychological violence showed similar moderately weak associations with drug use disorders (8% minimum risk increase), migraine (7%) and gynaecological diseases (2%). Neglect was linked to at least a 15% increased risk for anxiety disorders. The other 18 associations were weaker due to smaller effect sizes and/or less consistent evidence. Despite the limitations of the existing evidence, our analysis highlights substantial health impacts for VAC survivors, underscoring the need for health system prioritization and continued efforts to eliminate all forms of VAC.</p

3D printing of pharmaceuticals for disease treatment

Three-dimensional (3D) printing or Additive manufacturing has paved the way for developing and manufacturing pharmaceuticals in a personalized manner for patients with high volume and rare diseases. The traditional pharmaceutical manufacturing process involves the utilization of various excipients to facilitate the stages of blending, mixing, pressing, releasing, and packaging. In some cases, these excipients cause serious side effects to the patients. The 3D printing of pharmaceutical manufacturing avoids the need for excessive excipients. The two major components of a 3D printed tablet or dosage form are polymer matrix and drug component alone. Hence the usage of the 3D printed dosage forms for disease treatment will avoid unwanted side effects and provide higher therapeutic efficacy. With respect to the benefits of the 3D printed pharmaceuticals, the present review was constructed by discussing the role of 3D printing in producing formulations of various dosage forms such as fast and slow releasing, buccal delivery, and localized delivery. The dosage forms are polymeric tablets, nanoparticles, scaffolds, and films employed for treating different diseases.</jats:p

Applicability of tricycle modelling in the simulation of aircraft steering system.

Aircraft nose wheel steering system is simulated on MATLAB–Simulink platform to understand the influence of tyre–ground interaction and aircraft ground dynamics on the steering behaviour of the aircraft. The aircraft steering system model generally includes the Nose Landing gear model, Aircraft Dynamics model and Tyre model. In most of the literature, bicycle modelling method is adapted with two main gears lumped together and a nose landing gear, whereas tricycle modelling method with all the three gears is more appropriate and accurate way of predicting the aircraft steering response. In the present work, the mathematical formulation for the tricycle model is developed and it is observed that the resultant equations are non-linear and coupled, whereas the bicycle model is represented with linear and coupled equations. For the same inputs parameters, both tricycle and bicycle models are simulated. Results obtained from both the models are within 5% difference with the introduction of additional non-linearity in the tricycle modelling. Hence for aircraft with nose wheel steering, bicycle method is sufficient for predicting steering response but for the all-wheel steering system (steering on both nose and main landing gear), it is more appropriate to use the tricycle modelling method to predict the accurate steering response

ScELA: Scalable and Extensible Launching Architecture for Clusters ⋆

Abstract. As cluster sizes head into tens of thousands, current job launch mechanisms do not scale as they are limited by resource constraints as well as performance bottlenecks. The job launch process includes two phases – spawning of processes on processors and information exchange between processes for job initialization. Implementations of various programming models follow distinct protocols for the information exchange phase. We present the design of a scalable, extensible and high-performance job launch architecture for very large scale parallel computing. We present implementations of this architecture which achieve a speedup of more than 700 % in launching a simple Hello World MPI application on 10, 240 processor cores and also scale to more than 3 times the number of processor cores compared to prior solutions.