Identification of a novel locus on 2q for autosomal dominant high-grade myopia.

PURPOSE. Myopia, or nearsightedness, is a visual disorder of high and growing prevalence in the United States and in other countries. Pathologic high myopia, or myopia of ≤-6.00 D, predisposes individuals to retinal detachment, macular degeneration, cataracts, and glaucoma. Autosomal dominant (AD) nonsyndromic high-grade myopia has been mapped to loci on 18p11.31, 12q21-q23, 17q21-q23, and 7q36. This is the report of significant linkage to a novel locus on the long arm of chromosome 2 in a large, multigenerational family with AD high-grade myopia. METHODS. The family contains 31 participating members (14 affected). The average spherical refractive error for affected individuals was -14.46 D (range, -7.25 to -27.00). Before a genome screening was undertaken, linkage to intragenic or flanking markers for the myopic genetic syndromes of Stickler syndrome types I, II, and III; Marfan syndrome; and juvenile glaucoma were ruled out. In addition, no linkage was found to the known AD high-grade myopia loci listed above. A full genome screen of the family was performed with 382 microsatellite markers with an average intermarker distance of 10 cM. SimWalk2 software was used for multipoint linkage analysis based on an AD model with a penetrance of 90% and a disease allele frequency of 0.01. RESULTS. Fine-point mapping with an additional nine custommade and five commercial markers yielded a maximum two-point lod score of 5.67 at marker D2S2348. Results of multipoint analysis indicate that the 1-unit support intervals for this new locus spans approximately 9.1 cM from (238.7 to 247.8 cM) on the chromosome 2 genetic map at q37.1. CONCLUSIONS. A novel locus for AD high-grade myopia has been determined, providing further evidence of genetic heterogeneity for this disorder

Colorectal cancer surgery in the very elderly patient: a systematic review of laparoscopic versus open colorectal resection.

INTRODUCTION: Colorectal cancer is the second most common cause of death from neoplastic disease in men and third in women of all ages. Globally, life expectancy is increasing, and consequently, an increasing number of operations are being performed on more elderly patients with the trend set to continue. Elderly patients are more likely to have cardiovascular and pulmonary comorbidities that are associated with increased peri-operative risk. They further tend to present with more locally advanced disease, more likely to obstruct or have disseminated disease. The aim of this review was to investigate the feasibility of laparoscopic colorectal resection in very elderly patients, and whether there are benefits over open surgery for colorectal cancer. METHODS: A systematic literature search was performed on Medline, Pubmed, Embase and Google Scholar. All comparative studies evaluating patients undergoing laparoscopic versus open surgery for colorectal cancer in the patients population over 85 were included. The primary outcomes were 30-day mortality and 30-day overall morbidity. Secondary outcomes were operating time, time to oral diet, number of retrieved lymph nodes, blood loss and 5-year survival. RESULTS: The search provided 1507 citations. Sixty-nine articles were retrieved for full text analysis, and only six retrospective studies met the inclusion criteria. Overall mortality for elective laparoscopic resection was 2.92% and morbidity 23%. No single study showed a significant difference between laparoscopic and open surgery for morbidity or mortality, but pooled data analysis demonstrated reduced morbidity in the laparoscopic group (p = 0.032). Patients undergoing laparoscopic surgery are more likely to have a shorter hospital stay and a shorter time to oral diet. CONCLUSION: Elective laparoscopic resection for colorectal cancer in the over 85 age group is feasible and safe and offers similar advantages over open surgery to those demonstrated in patients of younger ages

Integrated Geomechanical and Digital Photogrammetric Survey in the Study of Slope Instability Processes of a Flysch Sea Cliff (Debeli Rtic Promontory, Slovenia)

This work presents an integrated study approach that combines the results of a geomechanical survey with data obtained using digital photogrammetry (DP), to assess slope instability processes affecting a sea cliff at the Debeli Rtic promontory (Slovenia). The investigated cliff is 4-18 m-high and is made up of an alternation of sandstones and marlstones belonging to the Flysch Formation of Trieste, which is Eocene in age. The studied cliff was subjected to localized slope failures that occurred in the past and is currently subject to frequent rock collapses, thus resulting in its partial and episodic retreat. Field evidence acquired through a traditional survey was integrated with outputs of the DP technique based on 1399 images that were collected using both a commercial unmanned aerial vehicle (UAV) and a mobile phone (MP). UAV-derived images were useful for performing rock mass structure analysis in the upper part of the investigated cliff, where the traditional survey was not possible due to hazardous operating conditions. In addition, the use of a MP was observed to be a useful tool for the rapid collection of images at the toe of unsafe marine cliff environments. This study highlights that UAV-DP and MP-DP techniques can only be effective if the outcomes obtained from the 3D model reconstruction are validated by direct measurements acquired by means of the traditional field survey, thus avoiding improper or even erroneous results while enlarging the amount of data and the area of investigation. The study approach presented herein allowed for the assessment of slope instabilities affecting the Flysch Sea cliff, whose retreat is caused by the combined action of marine erosion and slope gravitational processes

Integrated Geomechanical and Digital Photogrammetric Survey in the Study of Slope Instability Processes of a Flysch Sea Cliff (Debeli Rtič Promontory, Slovenia)

This work presents an integrated study approach that combines the results of a geomechanical survey with data obtained using digital photogrammetry (DP), to assess slope instability processes affecting a sea cliff at the Debeli Rtič promontory (Slovenia). The investigated cliff is 4–18 m-high and is made up of an alternation of sandstones and marlstones belonging to the Flysch Formation of Trieste, which is Eocene in age. The studied cliff was subjected to localized slope failures that occurred in the past and is currently subject to frequent rock collapses, thus resulting in its partial and episodic retreat. Field evidence acquired through a traditional survey was integrated with outputs of the DP technique based on 1399 images that were collected using both a commercial unmanned aerial vehicle (UAV) and a mobile phone (MP). UAV-derived images were useful for performing rock mass structure analysis in the upper part of the investigated cliff, where the traditional survey was not possible due to hazardous operating conditions. In addition, the use of a MP was observed to be a useful tool for the rapid collection of images at the toe of unsafe marine cliff environments. This study highlights that UAV-DP and MP-DP techniques can only be effective if the outcomes obtained from the 3D model reconstruction are validated by direct measurements acquired by means of the traditional field survey, thus avoiding improper or even erroneous results while enlarging the amount of data and the area of investigation. The study approach presented herein allowed for the assessment of slope instabilities affecting the Flysch Sea cliff, whose retreat is caused by the combined action of marine erosion and slope gravitational processes

Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex

Introduction: Disulfiram has been claimed to be useful in cocaine addiction therapy, its efficacy being attributed to dopamine-beta-hydroxylase (DBH) inhibition. Our previous results indicate that disulfiram and the selective DBH inhibitor nepicastat increase extracellular dopamine (DA) in the rat medial prefrontal cortex (mPFC), and markedly potentiated cocaine-induced increase. Concomitantly, in rats with cocaine self-administration history, cocaine-seeking behavior induced by drug priming was prevented, probably through overstimulation of D1 receptors due to the DA increase. The present research was aimed at studying the neurochemical mechanisms originating the enhanced DA release. Methods: Noradrenergic system ablation was attained by intracerebroventricular (i.c.v.) administration of the neurotoxin anti-DBH-saporin (aDBH-sap). DA, noradrenaline (NA), and DOPAC were assessed by HPLC after ex vivo tissue extraction or in vivo microdialysis. Control and denervated rats were subjected to microdialysis in the mPFC and caudate nucleus to evaluate the effect of nepicastat-cocaine combination on extracellular DA levels and their regulation by α2-adrenoceptors. Results: Fifteen days after neurotoxin or its vehicle administration, tissue and extracellular NA were reduced to less than 2% the control value, while extracellular DA was increased by approximately 100%. In control rats, nepicastat given alone and in combination with cocaine increased extracellular DA by about 250% and 1100%, respectively. In denervated rats, nepicastat slightly affected extracellular DA, while in combination with cocaine increased extracellular DA by 250%. No differences were found in the caudate nucleus. Clonidine almost totally reversed the extracellular DA elevation produced by nepicastat-cocaine combination, while it was ineffective in denervated rats. Conclusions: This research shows that the increase of extracellular DA produced by nepicastat alone or in combination with cocaine was prevented by noradrenergic denervation. The results indicate that nepicastat enhances DA release from noradrenergic terminals supposedly by removing NA from α2-autoreceptors. In addition to the inhibition of DA uptake, the latter mechanism may explain the synergistic effect of cocaine on nepicastat-induced DA release

Hungry brains: A meta-analytical review of brain activation imaging studies on food perception and appetite in obese individuals

The dysregulation of food intake in chronic obesity has been explained by different theories. To assess their explanatory power, we meta-analyzed 22 brain-activation imaging studies. We found that obese individuals exhibit hyper-responsivity of the brain regions involved in taste and reward for food-related stimuli. Consistent with a Reward Surfeit Hypothesis, obese individuals exhibit a ventral striatum hyper-responsivity in response to pure tastes, particularly when fasting. Furthermore, we found that obese subjects display more frequent ventral striatal activation for visual food cues when satiated: this continued processing within the reward system, together with the aforementioned evidence, is compatible with the Incentive Sensitization Theory. On the other hand, we did not find univocal evidence in favor of a Reward Deficit Hypothesis nor for a systematic deficit of inhibitory cognitive control. We conclude that the available brain activation data on the dysregulated food intake and food-related behavior in chronic obesity can be best framed within an Incentive Sensitization Theory. Implications of these findings for a brain-based therapy of obesity are briefly discussed

Using texture analysis in the development of a potential radiomic signature for early identification of hepatic metastasis in colorectal cancer

Background: Radiomics allows information not readily available to the naked eye to be extracted from high resolution imaging modalities such as CT. Identifying that a cancer has already metastasised at the time of presentation through a radiomic signature will affect the treatment pathway. The ability to recognise the existence of metastases earlier will have a significant impact on the survival outcomes. / Aim: To create a novel radiomic signature using textural analysis in the evaluation of synchronous liver metastases in colorectal cancer. / Methods: CT images at baseline and subsequent surveillance over a 5-year period of patients with colorectal cancer were processed using textural analysis software. Comparison was made between those patients who developed liver metastases and those that remained disease free to detect differences in the ‘texture’ of the liver. / Results: A total of 24 patients were divided into two matched groups for comparison. Significant differences between the two groups scores when using the textural analysis programme were found on coarse filtration (p = 0.044). Patients that went on to develop metastases an average of 18 months after presentation had higher levels of hepatic heterogeneity on CT. / Conclusion: This initial study demonstrates the potential of using a textural analysis programme to build a radiomic signature to predict the development of hepatic metastases in rectal cancer patients otherwise thought to have clear staging CT scans at time of presentation

Genetic linkage study of high-grade myopia in a Hutterite population from South Dakota

PURPOSE: Myopia is a common, complex disorder, and severe forms have implications for blindness due to increased risk of premature cataracts, glaucoma, retinal detachment, and macular degeneration. Autosomal dominant (AD) non-syndromic high-grade myopia has been mapped to chromosomes 18p11.31, 12q21-23, 17q21-23, 7q36, 2q37.1, 7p15.3, 15q12-13, 3q26, 4q12, 8p23, 4q22-q27, 1p36, and Xq23-q25. Here, we demonstrate evidence of linkage for AD non-syndromic high-grade myopia in a large Hutterite family to a locus on chromosome 10q21.1. METHODS: After clinical evaluation, genomic DNA was genotyped from 29 members of a Hutterite family from South Dakota (7 affected). The average refractive error of affected individuals was -7.04 diopters. Microsatellite markers were used to exclude linkage to the known AD nonsyndromic high-grade myopia loci as well as to syndromic high-grade myopia loci. A genome screen was then performed using 382 markers with an average inter-marker distance of 10 cM followed by fine-point mapping in all regions of the genome that gave positive LOD scores. SimWalk2 software was used for multipoint linkage based on AD and autosomal recessive (AR) models with a penetrance of 90% and a disease allele frequency of 0.001. RESULTS: A maximum multipoint LOD score of 3.22 was achieved under an AD model at microsatellite marker D10S1643. Fine point mapping and haplotype analysis defined a critical region of 2.67 cM on chromosome 10q21.1. Haplotype analysis demonstrated two distinct haplotypes segregating with high-grade myopia, indicative of two distinct mutations occurring in the same gene. CONCLUSIONS: We have identified a presumptive myopia locus for high-grade myopia based on linkage and haplotype analysis

On the Truncated Pareto Distribution with applications

The Pareto probability distribution is widely applied in different fields such us finance, physics, hydrology, geology and astronomy. This note deals with an application of the Pareto distribution to astrophysics and more precisely to the statistical analysis of mass of stars and of diameters of asteroids. In particular a comparison between the usual Pareto distribution and its truncated version is presented. Finally a possible physical mechanism that produces Pareto tails for the distribution of the masses of stars is suggested.Comment: 10 pages 6 figure

High energy photon-neutrino elastic scattering

The one-loop helicity amplitudes for the elastic scattering process $\gamma\nu\to\gamma\nu$ in the Standard Model are computed at high center of mass energies. A general decomposition of the amplitudes is utilized to investigate the validity of some of the key features of our results. In the center of mass, where $\sqrt{s} = 2\omega$, the cross section grows roughly as $\omega^6$ to near the threshold for $W$-boson production, $\sqrt{s} = m_W$. Although suppressed at low energies, we find that the elastic cross section exceeds the cross section for $\gamma\nu\to\gamma\gamma\nu$ when $\sqrt{s}>13$ GeV. We demonstrate that the scattered photons are circularly polarized and the net value of the polarization is non-zero. Astrophysical implications of high energy photon-neutrino scattering are discussed.Comment: 9 pages, 7 figures, RevTeX