La planificación estratégica y su incidencia en el nivel de competitividad empresarial de Exportaciones Agro Perales S.A.C. – Casma 2019

En el mundo globalizado donde vivimos y donde las MYPES desarrollan sus actividades; existen diversos factores que influyen directa o indirectamente en el nivel de competitividad que tienen en relación a su competencia y que tan preparada se encuentran estas para hacerle frente a los cambios que se dan en el entorno donde desarrollan sus actividades. La presente tesis titulada “La Planificación Estratégica y su Incidencia en el nivel de Competitividad Empresarial de Exportaciones Agro Perales S.A.C. – Casma 2019. Fue realizada con el objetivo de determinar la incidencia de la planificación estratégica en el nivel de competitividad empresarial de Exportaciones Agro Perales S.A.C- Casma 2019. Con el objetivo planteado, el problema de investigación es la siguiente: ¿Existe incidencia de la planificación estratégica en el nivel de competitividad empresarial de Exportaciones Agro Perales S.A.C.- Casma 2019?; Para realizar la investigación el tipo de estudio que se utilizó es correlacional – de diseño No experimental – de corte transversal. La muestra estuvo conformada por los 40 trabajadores que laboran en la empresa Exportaciones Agro Perales S.A.C. La técnica para la recolección de datos fue la encuesta, y el instrumento un cuestionario para cada variable, el cual fue aplicado a todos los trabajadores de la empresa. Para determinar la incidencia de la planificación estratégica en el nivel de competitividad Empresarial; se calculó el coeficiente de correlación de Spearman el cual arrojó una Rho de 0.780; lo que significa que existe una incidencia alta positiva fuerte de la Planificación Estratégica en el Nivel de competitividad empresarial de Exportaciones Agro Perales S.A.C. Casma 2019

Genetically Confirmed Familial Hypercholesterolemia in Patients With Acute Coronary Syndrome

BACKGROUND: Genetic screening programs in unselected individuals with increased levels of low-density lipoprotein cholesterol (LDL-C) have shown modest results in identifying individuals with familial hypercholesterolemia (FH). OBJECTIVES: This study assessed the prevalence of genetically confirmed FH in patients with acute coronary syndrome (ACS) and compared the diagnostic performance of FH clinical criteria versus FH genetic testing. METHODS: Genetic study of 7 genes (LDLR, APOB, PCSK9, APOE, STAP1, LDLRAP1, and LIPA) associated with FH and 12 common alleles associated with polygenic hypercholesterolemia was performed in 103 patients with ACS, age ≤65 years, and LDL-C levels ≥160 mg/dl. Dutch Lipid Clinic (DLC) and Simon Broome (SB) FH clinical criteria were also applied. RESULTS: The prevalence of genetically confirmed FH was 8.7% (95% confidence interval [CI]: 4.3% to 16.4%; n = 9); 29% (95% CI: 18.5% to 42.1%; n = 18) of patients without FH variants had a score highly suggestive of polygenic hypercholesterolemia. The prevalence of probable to definite FH according to DLC criteria was 27.2% (95% CI: 19.1% to 37.0%; n = 28), whereas SB criteria identified 27.2% of patients (95% CI: 19.1% to 37.0%; n = 28) with possible to definite FH. DLC and SB algorithms failed to diagnose 4 (44%) and 3 (33%) patients with genetically confirmed FH, respectively. Cascade genetic testing in first-degree relatives identified 6 additional individuals with FH. CONCLUSIONS: The prevalence of genetically confirmed FH in patients with ACS age ≤65 years and with LDL-C levels ≥160 mg/dl is high (approximately 9%). FH clinical algorithms do not accurately classify patients with FH. Genetic testing should be advocated in young patients with ACS and high LDL-C levels to allow prompt identification of patients with FH and relatives at risk.This research was supported in part by the Instituto de Salud Carlos III (grants RD012/0042/0066 and CB16/11/00432), Spanish Ministry of Economy and Competitiveness (grant SAF2015-71863-REDT), and Alexion through an Investigator Initiated Research Grant. Grants from the Instituto de Salud Carlos III and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de I+D+I 2013-2016 European Regional Development Fund (FEDER), "A way of making Europe." The sponsors played no role in the design, collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Drs. Castillo, Lluis-Ganella, and Quintana are employees of Gendiag.exe/Ferrer inCode.S

Marginal role for 53 common genetic variants in cardiovascular disease prediction.

OBJECTIVE: We investigated discrimination and calibration of cardiovascular disease (CVD) risk scores when genotypic was added to phenotypic information. The potential of genetic information for those at intermediate risk by a phenotype-based risk score was assessed. METHODS: Data were from seven prospective studies including 11 851 individuals initially free of CVD or diabetes, with 1444 incident CVD events over 10 years' follow-up. We calculated a score from 53 CVD-related single nucleotide polymorphisms and an established CVD risk equation 'QRISK-2' comprising phenotypic measures. The area under the receiver operating characteristic curve (AUROC), detection rate for given false-positive rate (FPR) and net reclassification improvement (NRI) index were estimated for gene scores alone and in addition to the QRISK-2 CVD risk score. We also evaluated use of genetic information only for those at intermediate risk according to QRISK-2. RESULTS: The AUROC was 0.635 for QRISK-2 alone and 0.623 with addition of the gene score. The detection rate for 5% FPR improved from 11.9% to 12.0% when the gene score was added. For a 10-year CVD risk cut-off point of 10%, the NRI was 0.25% when the gene score was added to QRISK-2. Applying the genetic risk score only to those with QRISK-2 risk of 10%-<20% and prescribing statins where risk exceeded 20% suggested that genetic information could prevent one additional event for every 462 people screened. CONCLUSION: The gene score produced minimal incremental population-wide utility over phenotypic risk prediction of CVD. Tailored prediction using genetic information for those at intermediate risk may have clinical utility

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

The impact of early postnatal environmental enrichment on maternal care and offspring behaviour following weaning

The early postnatal period is a sensitive period in rodents as behavioural systems are developing and maturing during this time. However, relatively little information is available about the impact of environmental enrichment on offspring behaviour if enrichment is implemented only during this period. Here, environmental enrichment was provided from postnatal day 1 until weaning. On post-natal day 9, maternal behaviour and nonmaternal behaviour of the dam was observed. Nursing time in the enriched group was reduced but dams showed more non-maternal appetitive behaviours. Offspring were exposed to either the open field or the elevated plus maze (EPM) after weaning. In the open field, rats from the enriched group approached the more aversive inner zone of the open field later than control rats. Offspring from the enriched group made fewer entries into the inner zone and spent less time in this part of the arena. Enrichment had no impact on behaviour in the EPM. The present study provides evidence that postnatal enrichment can interfere with maternal behaviour in rats and can possibly lead to increased anxiety in the offspring. The findings suggest that enrichment procedures can have potentially unintended effects, interfering with the development of emotional behaviours in rats

Large Scale Association Analysis Identifies Three Susceptibility Loci for Coronary Artery Disease

Genome wide association studies (GWAS) and their replications that have associated DNA variants with myocardial infarction (MI) and/or coronary artery disease (CAD) are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3), and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR = 0.68, p = 0.0035), while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR = 1.33, p = 0.0086). Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology

Optimising exposure for children and adolescents with anxiety, OCD and PTSD: a systematic review

Cognitive-behavioural therapy is an effective treatment for anxiety disorders in children and young people, however, many do not benefit. Behavioural exposure appears to be the critical ingredient in the treatment of anxiety disorders. Research with adults has identified innovative strategies to optimise exposure-based treatments, yet it is not clear how to optimise the effects of exposure for children and young people. This review was a preliminary exploration of the association between potential optimisation strategies and treatment procedures and outcomes for the treatment of child anxiety symptoms/disorders. We searched PsychInfo and Medline databases using a systematic search strategy and identified 29 articles. We found preliminary evidence that some specific strategies may enhance the effects of exposure, such as dropping safety behaviours, parents and therapists discouraging avoidance, and the use of homework. However, not one significant finding was replicated by another study for the same time point using the same methodology. To a large degree, this lack of replication reflects a limited number of studies combined with a lack of consistency across studies around conceptualisations, methodological approaches, and outcome measures making it difficult to make meaningful comparisons between studies and draw firm conclusions. Examination is needed of a wide range of theoretically-driven potential optimisation strategies using methodologically robust, preclinical studies with children and young people. Furthermore, the methods used in future research must enable comparisons across studies and explore developmental differences in the effects of particular optimisation strategies

Functional brain networks in schizophrenia: mapping connectivity and topology at early and late psychotic illness stages

© 2017 Dr. Eleni GanellaSchizophrenia is a severe mental disorder that is characterised by symptoms including hallucinations, delusions and disorganized thought. The cause of schizophrenia remains unknown; however, it is thought that a combination of genetics, environment and altered neurobiology play a role in the emergence and perpetuation of the disorder. Accumulating evidence suggests that disrupted brain network connectivity may in part underlie the pathophysiology of psychosis, and that network connectivity is to some extent genetically determined and heritable. However, there is still much to be learned surrounding the nature of network abnormalities and how they differ in early versus late psychosis. Exploring the underlying neurobiology at discrete clinical stages of psychotic illness creates a framework to evaluate the biological factors that may be contributing to the progression from early psychosis, to more advanced chronic stages of the disorder. This thesis used resting-state functional magnetic resonance imaging (fMRI) to characterise network functional connectivity and topology in early and late psychosis, as well as in a group of unaffected family members (UFM) of individuals with schizophrenia. Resting-state fMRI is a well validated and sensitive tool for probing the intrinsic functional integrity of the brain. Specifically, this thesis used a data-driven approach to map the temporal coherence of fMRI time series (functional connectivity) across the whole brain. To complement the resting-state functional connectivity (rs-FC) analysis, this thesis used graph theory to explore functional network topology. Network topology describes that brains ability to maintain a balance between local processing speed and global integration of information. These methodological approaches were used to investigate network abnormalities in three groups relative to healthy controls; a first-episode psychosis (FEP) group, a treatment-resistant schizophrenia (TRS) group and a group of UFM. This thesis aimed to investigate 1) whether rs-FC and network topology was abnormal in the early FEP stage of schizophrenia relative to healthy controls at two time-points (baseline and at 12-months follow-up); 2) whether rs-FC and network topology was impaired in a chronic TRS group relative to healthy controls; 3) whether abnormal rs-FC and network topology was evident in a group of UFM, and whether any network measure could be characterised as a marker of risk or resilience to psychosis in UFM. Firstly, results showed no evidence of abnormal rs-FC or topology in FEP individuals relative to healthy controls at baseline, or at the 12-months follow-up. Further, longitudinal changes in network properties over a 12-month period did not significantly differ between FEP individuals and healthy controls. Secondly, this thesis found widespread reductions in rs-FC in the TRS group that predominantly involved temporal, occipital and frontal brain regions. The TRS group also showed reduced global network efficiency and increased local efficiency relative to controls. Thirdly, TRS and UFM shared frontal and occipital rs-FC deficits, representing a ‘risk’ endophenotype. Additional reductions in frontal and temporal rs-FC appeared to be associated with risk that precipitates psychosis in vulnerable individuals, or may be due to other illness-related effects, such as medication. Functional brain networks were more topologically resilient in UFM compared to TRS, which may protect UFM from psychosis onset despite familial liability. Together, the body of work presented in this thesis provides a number of novel and unique findings that serve to advance the current state of knowledge regarding the pathophysiology and heritability of psychosis. Specifically, the work demonstrated that the latest most severe stage of psychosis, TRS, is associated with widespread reduced rs-FC, and that milder, yet similar patterns of dysconnectivity were observed in UFM, implying a genetic root to some, but not all of the observed network abnormalities. Network topology differed relative to healthy controls in both UFM and TRS patients, suggesting that functional network architecture is also disturbed in late psychosis, and again, results suggest a genetic/shared environmental basis for this characteristic. Our finding of no significant difference in rs-FC or network topology in our FEP sample suggests that there is a differentiation between biological processes occurring in early and late psychosis with a subgroup of individuals’ rs-FC potentially being unaffected in the FEP stage