General models in min-max continous location

In this paper, a class of min-max continuous location problems is discussed. After giving a complete characterization of th stationary points, we propose a simple central and deep-cut ellipsoid algorithm to solve these problems for the quasiconvex case. Moreover, an elementary convergence proof of this algorithm and some computational results are presented

Emotion-Related Visual Mismatch Responses in Schizophrenia: Impairments and Correlations with Emotion Recognition.

BACKGROUND AND OBJECTIVES:Mismatch negativity (MMN) is an event-related potential (ERP) measure of preattentional sensory processing. While deficits in the auditory MMN are robust electrophysiological findings in schizophrenia, little is known about visual mismatch response and its association with social cognitive functions such as emotion recognition in schizophrenia. Our aim was to study the potential deficit in the visual mismatch response to unexpected facial emotions in schizophrenia and its association with emotion recognition impairments, and to localize the sources of the mismatch signals. EXPERIMENTAL DESIGN:The sample comprised 24 patients with schizophrenia and 24 healthy control subjects. Controls were matched individually to patients by gender, age, and education. ERPs were recorded using a high-density 128-channel BioSemi amplifier. Mismatch responses to happy and fearful faces were determined in 2 time windows over six regions of interest (ROIs). Emotion recognition performance and its association with the mismatch response were also investigated. PRINCIPAL OBSERVATIONS:Mismatch signals to both emotional conditions were significantly attenuated in patients compared to controls in central and temporal ROIs. Controls recognized emotions significantly better than patients. The association between overall emotion recognition performance and mismatch response to the happy condition was significant in the 250-360 ms time window in the central ROI. The estimated sources of the mismatch responses for both emotional conditions were localized in frontal regions, where patients showed significantly lower activity. CONCLUSIONS:Impaired generation of mismatch signals indicate insufficient automatic processing of emotions in patients with schizophrenia, which correlates strongly with decreased emotion recognition

Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development

CONTEXT: Genetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM). OBJECTIVE: We assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy. METHODS: 960 pregnant women (after dropouts 820: case/control: m99'WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study. After genomic DNA isolation the 820 samples were collected in a GDM biobank and assessed using KASP (LGC Genomics) genotyping assay. Logistic regression risk models were used to calculate ORs according to IADPSG/m'99WHO criteria based on standard OGTT values. RESULTS: The most important risk alleles associated with GDM were rs10830963/G of MTNR1B (OR = 1.84/1.64 [IADPSG/m'99WHO], p = 0.0007/0.006), rs7754840/C (OR = 1.51/NS, p = 0.016) of CDKAL1 and rs1799884/T (OR = 1.4/1.56, p = 0.04/0.006) of GCK. The rs13266634/T (SLC30A8, OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/G (LOC646736/IRS1, OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM. Carrying a minor allele of rs10830963 (MTNR1B); rs7903146 (TCF7L2); rs1799884 (GCK) SNPs were associated with increased plasma glucose levels at routine OGTT. CONCLUSIONS: We confirmed the robust association of MTNR1B rs10830963/G variant with GDM binary and glycemic traits in this Caucasian case-control study. As novel associations we report the minor, G allele of the rs7578326 SNP in the LOC646736/IRS1 region as a significant and the rs13266634/T SNP (SLC30A8) as a suggestive protective variant against GDM development. Genetic susceptibility appears to be more preponderant in individuals who meet both the modified 99'WHO and the IADPSG GDM diagnostic criteria

SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer

<p>Abstract</p> <p>Background</p> <p>Association between rectal or colon cancer risk and serine hydroxymethyltransferase 1 (<it>SHMT1</it>) C1420T or methylenetetrahydrofolate reductase (<it>MTHFR</it>) C677T polymorphisms was assessed. The serum total homocysteine (HCY), marker of folate metabolism was also investigated.</p> <p>Methods</p> <p>The <it>SHMT1 </it>and <it>MTHFR </it>genotypes were determined by real-time PCR and PCR-RFLP, respectively in 476 patients with rectal, 479 patients with colon cancer and in 461 and 478, respective controls matched for age and sex. Homocysteine levels were determined by HPLC kit. The association between polymorphisms and cancer risk was evaluated by logistic regression analysis adjusted for age, sex and body mass index. The population stratification bias was also estimated.</p> <p>Results</p> <p>There was no association of genotypes or diplotypes with colon cancer. The rectal cancer risk was significantly lower for <it>SHMT1 </it>TT (OR = 0.57, 95% confidence interval (CI) 0.36-0.89) and higher for <it>MTHFR </it>CT genotypes (OR = 1.4, 95%CI 1.06-1.84). A gene-dosage effect was observed for <it>SHMT1 </it>with progressively decreasing risk with increasing number of T allele (p = 0.014). The stratified analysis according to age and sex revealed that the association is mainly present in the younger (< 60 years) or male subgroup. As expected from genotype analysis, the <it>SHMT1 </it>T allele/<it>MTHFR </it>CC diplotype was associated with reduced rectal cancer risk (OR 0.56, 95%CI 0.42-0.77 vs all other diplotypes together). The above results are unlikely to suffer from population stratification bias. In controls HCY was influenced by <it>SHMT1 </it>polymorphism, while in patients it was affected only by Dukes' stage. In patients with Dukes' stage C or D HCY can be considered as a tumor marker only in case of <it>SHMT1 </it>1420CC genotypes.</p> <p>Conclusions</p> <p>A protective effect of <it>SHMT1 </it>1420T allele or <it>SHMT1 </it>1420 T allele/<it>MTHFR </it>677 CC diplotype against rectal but not colon cancer risk was demonstrated. The presence of <it>SHMT1 </it>1420 T allele significantly increases the HCY levels in controls but not in patients. Homocysteine could be considered as a tumor marker in <it>SHMT1 </it>1420 wild-type (CC) CRC patients in Dukes' stage C and D. Further studies need to clarify why <it>SHMT1 </it>and <it>MTHFR </it>polymorphisms are associated only with rectal and not colon cancer risk.</p

Restoring brain function after stroke - bridging the gap between animals and humans

Stroke is the leading cause of complex adult disability in the world. Recovery from stroke is often incomplete, which leaves many people dependent on others for their care. The improvement of long-term outcomes should, therefore, be a clinical and research priority. As a result of advances in our understanding of the biological mechanisms involved in recovery and repair after stroke, therapeutic opportunities to promote recovery through manipulation of poststroke plasticity have never been greater. This work has almost exclusively been carried out in preclinical animal models of stroke with little translation into human studies. The challenge ahead is to develop a mechanistic understanding of recovery from stroke in humans. Advances in neuroimaging techniques now enable us to reconcile behavioural accounts of recovery with molecular and cellular changes. Consequently, clinical trials can be designed in a stratified manner that takes into account when an intervention should be delivered and who is most likely to benefit. This approach is expected to lead to a substantial change in how restorative therapeutic strategies are delivered in patients after stroke

A Multidimensional, Comparative Analysis of the Regional Entrepreneurship Performance in the Central and Eastern European EU Member Countries

Entrepreneurship research has changed considerably over the last 30 years, and today entrepreneurship is widely accepted as a major driving force of economic development, of the creation of employment and of innovation (Acs et al. 2008, 2009; Carree and Thurik 2003; Braunerhjelm et al. 2010; Lazear 2004). However, the dynamics of the effect of entrepreneurship are very diverse and depend on many factors such as the development level of the home country and the institutional context (Acs et al. 2008). Whilst previous studies on entrepreneurship have focused on examining the role of entrepreneurial activity and start-up rates, recent research has shown that not all entrepreneurial activity is effective. High growth rates, such as those achieved by innovative gazelle companies, are responsible for the bulk of new job creation and growth, whilst other non-innovative or traditional businesses have only minor economic influence (Acs and Mueller 2008; Baumol 1996; Wong et al. 2005)

On the Scalarization of Pseudoconcavity and Pseudomonotonicity Concepts for Vector Valued Functions

In this paper we continue the study of polar generalized convexity of vector valued functions initiated in [6]. Our aim now is to give first order characterization for special classes of vector valued directionally differentiable pseudoconcave functions in terms of suitable pseudomonotonicity property of the directional derivative