Quantum dynamics in strong fluctuating fields

A large number of multifaceted quantum transport processes in molecular systems and physical nanosystems can be treated in terms of quantum relaxation processes which couple to one or several fluctuating environments. A thermal equilibrium environment can conveniently be modelled by a thermal bath of harmonic oscillators. An archetype situation provides a two-state dissipative quantum dynamics, commonly known under the label of a spin-boson dynamics. An interesting and nontrivial physical situation emerges, however, when the quantum dynamics evolves far away from thermal equilibrium. This occurs, for example, when a charge transferring medium possesses nonequilibrium degrees of freedom, or when a strong time-dependent control field is applied externally. Accordingly, certain parameters of underlying quantum subsystem acquire stochastic character. Herein, we review the general theoretical framework which is based on the method of projector operators, yielding the quantum master equations for systems that are exposed to strong external fields. This allows one to investigate on a common basis the influence of nonequilibrium fluctuations and periodic electrical fields on quantum transport processes. Most importantly, such strong fluctuating fields induce a whole variety of nonlinear and nonequilibrium phenomena. A characteristic feature of such dynamics is the absence of thermal (quantum) detailed balance.Comment: review article, Advances in Physics (2005), in pres

Scrotal metastases from colorectal carcinoma: a case report

A 72-year-old man presented with a two month history of rectal bleeding. Colonoscopy demonstrated synchronous lesions at 3 cm and 40 cm with histological analysis confirming synchronous adenocarcinomata. He developed bilobar hepatic metastases while undergoing neoadjuvant chemoradiotherapy. Treatment was complicated by Fournier's gangrene of the right hemiscrotum which required surgical debridement. Eight months later he re-presented with an ulcerating lesion on the right hemiscrotum. An en-bloc resection of the ulcerating scrotal lesion and underlying testis was performed. Immunohistological analysis revealed metastatic adenocarcinoma of large bowel origin. Colorectal metastasis to the urogenital tract is rare and here we report a case of rectal carcinoma metastasizing to scrotal skin

Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Case of a sigmoid colon cancer with metachronous metastases to the mesorectum and the abdominal wall

<p>Abstract</p> <p>Backround</p> <p>Sigmoid colon cancer metachronous metastases commonly occur in the liver and lungs with sporadic reports also to the spleen, stomach, thyroid gland, abdominal wall and upper urinary tract. This is a rare case of metachronous metastases invading the mesorectum and the abdominal wall.</p> <p>Case presentation</p> <p>A 72-year-old female underwent sigmoidectomy for stage I (T2N0 M0) sigmoid colon cancer in May 2008. In June 2009, an abdominal computed tomography scan revealed a tumor 2 cm in size at the lower anterior mesorectum and a second mass 2 cm in size at the anterior abdominal wall midline. Total colonoscopy showed no mucosal lesion. The serum carcinoembryonic antigen level was normal. A biopsy of the mesorectum tumor showed similar histologic characteristics with the primary tumor. Since no other site of recurrence was identified, an abdominoperineal resection was attempted. During the operation and after the removal of the incision recurrence, sinus bradycardia and signs of myocardial ischemia were noticed. A loop transverse colostomy was immediately perfomed and the operation was terminated. Postoperative cardiologic examination revealed an acute myocardium infract. Chemo-radiation of the mesorectum tumor and re-evaluation for surgical excision was decided.</p> <p>Conclusion</p> <p>Metachronous metastasis of the mesorectum from sigmoid colon cancer is extremely rare. Although patterns of lymphatic spread from rectal cancer to sigmoid colon have recently been demonstrated, there is no evidence of metachronous mesorectum invasion from sigmoid colon cancer. This could be the issue for future trials.</p

A self administered reliable questionnaire to assess lower bowel symptoms

<p>Abstract</p> <p>Background</p> <p>Bowel symptoms are considered indicators of the presence of colorectal cancer and other bowel diseases. Self administered questionnaires that elicit information about lower bowel symptoms have not been assessed for reliability, although this has been done for upper bowel symptoms. Our aim was to develop a self administered questionnaire for eliciting the presence, nature and severity of lower bowel symptoms potentially related to colorectal cancer, and assess its reliability.</p> <p>Methods</p> <p>Immediately before consulting a gastroenterologist or colorectal surgeon, 263 patients likely to have a colonoscopy completed the questionnaire. Reliability was assessed in two ways: by assessing agreement between patient responses and (a) responses given by the doctor at the consultation; and (b) responses given by patients two weeks later.</p> <p>Results</p> <p>There was more than 75% agreement for 78% of the questions for the patient-doctor comparison and for 92% of the questions for the patient-patient comparison. Agreement for the length of time a symptom was present, its severity, duration, frequency of occurrence and whether or not medical consultation had been sought, all had agreement of greater than 70%. Over all questions, the chance corrected agreement for the patient-doctor comparison had a median kappa of 65% (which represents substantial agreement), interquartile range 57–72%. The patient-patient comparison also showed substantial agreement with a median kappa of 75%, interquartile range 68–81%.</p> <p>Conclusion</p> <p>This self administered questionnaire about lower bowel symptoms is a useful way of eliciting details of bowel symptoms. It is a reliable instrument that is acceptable to patients and easily completed. Its use could guide the clinical consultation, allowing a more efficient, comprehensive and useful interaction, ensuring that all symptoms are assessed. It will also be a useful tool in research studies on bowel symptoms and their predictive value for colorectal cancer and other diseases. Studies assessing whether bowel symptoms predict the presence of colorectal cancer should provide estimates of the reliability of the symptom elicitation.</p

Local Cattle and Badger Populations Affect the Risk of Confirmed Tuberculosis in British Cattle Herds

Background: The control of bovine tuberculosis (bTB) remains a priority on the public health agenda in Great Britain, after launching in 1998 the Randomised Badger Culling Trial (RBCT) to evaluate the effectiveness of badger (Meles meles) culling as a control strategy. Our study complements previous analyses of the RBCT data (focusing on treatment effects) by presenting analyses of herd-level risks factors associated with the probability of a confirmed bTB breakdown in herds within each treatment: repeated widespread proactive culling, localized reactive culling and no culling (survey-only). Methodology/Principal Findings: New cases of bTB breakdowns were monitored inside the RBCT areas from the end of the first proactive badger cull to one year after the last proactive cull. The risk of a herd bTB breakdown was modeled using logistic regression and proportional hazard models adjusting for local farm-level risk factors. Inside survey-only and reactive areas, increased numbers of active badger setts and cattle herds within 1500 m of a farm were associated with an increased bTB risk. Inside proactive areas, the number of M. bovis positive badgers initially culled within 1500 m of a farm was the strongest predictor of the risk of a confirmed bTB breakdown. Conclusions/Significance: The use of herd-based models provide insights into how local cattle and badger populations affect the bTB breakdown risks of individual cattle herds in the absence of and in the presence of badger culling. These measures of local bTB risks could be integrated into a risk-based herd testing programme to improve the targeting o

From monogenic to polygenic obesity: recent advances

The heritability of obesity and body weight in general is high. A small number of confirmed monogenic forms of obesity—the respective mutations are sufficient by themselves to cause the condition in food abundant societies—have been identified by molecular genetic studies. The elucidation of these genes, mostly based on animal and family studies, has led to the identification of important pathways to the disorder and thus to a deeper understanding of the regulation of body weight. The identification of inborn deficiency of the mostly adipocyte-derived satiety hormone leptin in extremely obese children from consanguineous families paved the way to the first pharmacological therapy for obesity based on a molecular genetic finding. The genetic predisposition to obesity for most individuals, however, has a polygenic basis. A polygenic variant by itself has a small effect on the phenotype; only in combination with other predisposing variants does a sizeable phenotypic effect arise. Common variants in the first intron of the ‘fat mass and obesity associated’ gene (FTO) result in an elevated body mass index (BMI) equivalent to approximately +0.4 kg/m² per risk allele. The FTO variants were originally detected in a genome wide association study (GWAS) pertaining to type 2 diabetes mellitus. Large meta-analyses of GWAS have subsequently identified additional polygenic variants. Up to December 2009, polygenic variants have been confirmed in a total of 17 independent genomic regions. Further study of genetic effects on human body weight regulation should detect variants that will explain a larger proportion of the heritability. The development of new strategies for diagnosis, treatment and prevention of obesity can be anticipated