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INTRODUCTION: The rate of community antibiotic use is high in Aotearoa New Zealand (NZ) when compared to other nations, and in NZ, as in most other nations, antibiotics are very commonly prescribed for self-limiting upper respiratory tract infections (URTIs). Resources that build knowledge, perceptions and understanding can potentially reduce unnecessary antibiotic consumption. METHODS: To inform the content of educational resources, we conducted an in-depth qualitative study with 47 participants via 6 focus groups of the knowledge, attitudes, and expectations of whanau Maori and Pacific peoples about antibiotics and URTIs. RESULTS: Focus groups with 47 participants identified four themes: Knowledge that might influence expectations to receive antibiotics for URTIs; Perceptions - the factors that influence when and why to seek medical care for URTI; Expectations - the features of successful medical care for URTI; Solutions - how to build community knowledge about URTI and their treatment and prevention. Knowledge that might reduce expectations to receive antibiotics for URTI included confidence in the use of alternative remedies, knowledge that URTI are usually caused by viruses, and concerns about antibiotic adverse effects. Participants commonly reported that they would confidently accept their doctor's recommendation that an antibiotic was not necessary for an URTI, provided that a thorough assessment had been performed and that treatment decisions were clearly communicated. CONCLUSION: These findings suggest that building patients' knowledge and skills about when antibiotics are necessary, and increasing doctors' confidence and willingness not to prescribe an antibiotic for patients with an URTI, could significantly reduce inappropriate antibiotic prescribing in NZ.
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Antibacterianos , Conocimientos, Actitudes y Práctica en Salud , Pueblo Maorí , Infecciones del Sistema Respiratorio , Humanos , Antibacterianos/uso terapéutico , Grupos Focales , Motivación , Investigación Cualitativa , Infecciones del Sistema Respiratorio/tratamiento farmacológicoRESUMEN
BACKGROUND: Evidence is emerging that the incidence of colorectal cancer is increasing in young adults, but the descriptive epidemiology required to better understand these trends is currently lacking. METHODS: A population-based cohort study was carried out including all adults aged 20-49 years diagnosed with colorectal cancer in England between 1974 and 2015. Data were extracted from the National Cancer Registration and Analysis Service database using ICD-9/10 codes for colorectal cancer. Temporal trends in age-specific incidence rates according to sex, anatomical subsite, index of multiple deprivation quintile and geographical region were analysed using Joinpoint regression. RESULTS: A total of 56 134 new diagnoses of colorectal cancer were analysed. The most sustained increase in incidence rate was in the group aged 20-29 years, which was mainly driven by a rise in distal tumours. The magnitude of incident rate increases was similar in both sexes and across Index of Multiple Deprivation quintiles, although the most pronounced increases in incidence occurred in the southern regions of England. CONCLUSION: Colorectal cancer should no longer be considered a disease of older people. Changes in incidence rates should be used to inform future screening policy, preventative strategies and research agendas, as well as increasing public understanding that younger people need to be aware of the symptoms of colorectal cancer.
ANTECEDENTES: Están apareciendo evidencias de que la incidencia del cáncer colorrectal (colorectal cancer, CRC) está aumentando en adultos jóvenes, pero se carece de la epidemiología descriptiva necesaria para comprender mejor estas tendencias. MÉTODOS: Se realizó un estudio de cohortes de base poblacional de todos los adultos de 20 a 49 años diagnosticados de CRC en Inglaterra entre 1974 y 2015. Los datos se extrajeron de la base de datos NCRAS utilizando los códigos ICD9/10 para el CRC. Las tendencias temporales en las tasas de incidencia específicas por edad (incidence rates, IR) según el sexo, la localización anatómica, el quintil del índice de privación múltiple (index of multiple deprivation, IMD) y la región geográfica se analizaron mediante un modelo de regresión joinpoint. RESULTADOS: Se analizaron un total de 56.134 nuevos diagnósticos de CRC. El aumento más sostenido en la IR se produjo en el grupo de edad de 20 a 29 años, principalmente a expensas de un incremento de los tumores distales. La magnitud de los aumentos de IR fue similar en ambos sexos y en los quintiles del IMD, aunque los aumentos más pronunciados en la incidencia se registraron en las regiones del sur de Inglaterra. CONCLUSIÓN: El CRC ya no debe ser considerado una enfermedad de las personas mayores: los cambios en las tasas de incidencia deberán tenerse en cuenta en las futuras políticas de cribado, en las estrategias preventivas y en los proyectos de investigación, así como para aumentar la toma de conciencia de la población de que las personas más jóvenes deben estar al corriente de los síntomas del CRC.
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Neoplasias Colorrectales/epidemiología , Adulto , Distribución por Edad , Edad de Inicio , Neoplasias Colorrectales/patología , Inglaterra/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Sistema de Registros , Distribución por Sexo , Adulto JovenRESUMEN
AIM: Advanced stage presentation of colorectal cancer is associated with poorer survival outcomes, particularly among young adults. This study aimed to determine whether demographic risk factors for advanced stage presentation differed between young and older adults. METHOD: Individual-level data on all incident colorectal cancers in people aged 20 years and above were extracted from the National Cancer Registration and Analysis Service database for the years 2012 to 2015. Patients were divided into two cohorts: young-onset colorectal cancer (YOCC) if aged 20-49 years and older-onset colorectal cancer (OOCC) if aged 50 years and above. Logistic regression was used to identify risk factors for advanced stage presentation, defined as TNM Stage III or IV, in each cohort. RESULTS: There were 7075 (5.2%) patients in the YOCC cohort and 128 345 (94.8%) patients in the OOCC cohort. Tumours in the YOCC cohort were more likely to be at an advanced stage (67.2% vs 55.3%, P < 0.001) and located distally (63.7% vs 55.4%, P < 0.001). No demographic factor was consistently associated with advanced stage presentation in the YOCC cohort. Among the OOCC cohort, increased social deprivation [OR (Index of Multiple Deprivation quintile 5 vs 1) = 1.11 (95% CI 1.07-1.16), P < 0.001], Black/Black British ethnicity [OR (baseline White) = 1.25 (95% CI 1.11-1.40), P < 0.001] and residence in the East Midlands [OR (baseline London) = 1.11 (95% CI 1.04-1.17), P = 0.001] were associated with advanced stage presentation. CONCLUSION: Demographic factors associated with advanced disease were influenced by age. The effects of social deprivation and ethnicity were only observed in older adults and mirror trends in screening uptake. Targeted interventions for high-risk groups are warranted.
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Neoplasias Colorrectales , Anciano , Estudios de Cohortes , Neoplasias Colorrectales/epidemiología , Inglaterra/epidemiología , Etnicidad , Humanos , Factores de RiesgoRESUMEN
Some livestock breeds face the challenge of reduced genetic variation, increased inbreeding depression owing to genetic drift and selection. Hybridization can reverse these processes and increase levels of productivity and adaptation to various environmental stressors. Samples from American Brangus were used to evaluate the indicine/taurine composition through nine generations (~45 years) after the hybridization process was completed. The purpose was to determine how hybridization alters allelic combinations of a breed over time when genetic factors such as selection and drift are operating. Furthermore, we explored genomic regions with deviations from the expected composition from the progenitor breeds and related these regions to traits under selection. The Brangus composition deviated from the theoretical expectation, defined by the breed association, of 62.5% taurine, showing taurine composition to be 70.4 ± 0.6%. Taurine and indicine proportion were not consistent across chromosomes. Furthermore, these non-uniform areas were found to be associated with traits that were probably under selection such as intermuscular fat and average daily gain. Interestingly, the sex chromosomes were predominantly taurine, which could be due to the composite being formed particularly in the final cross that resulted in progeny designated as purebred Brangus. This work demonstrated the process of new breed formation on a genomic level. It suggests that factors like genetic drift, selection and complementarity shift the genetic architecture into a uniquely different population. These findings are important to better understand how hybridization and crossbreeding systems shape the genetic architecture of composite populations.
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Cruzamiento , Bovinos/genética , Hibridación Genética , AnimalesRESUMEN
AIM: Total mesorectal excision remains the cornerstone of treatment for rectal cancer. Significant morbidity means local excision may be more appropriate in selected patients. Adjuvant therapy reduces local recurrence and improves survival; however, there is a paucity of data on its impact following local excision, which this systematic review aims to address. METHODS: A systematic search of the MEDLINE, Embase and Cochrane databases using validated terms for rectal cancer, adjuvant therapy and local excision was performed. Included studies focused on local excision with adjuvant therapy for adenocarcinoma of the rectum. Primary outcome measures were local recurrence, survival and morbidity. Studies providing neoadjuvant therapy or local excision alone were excluded. RESULTS: Twenty-two studies described 804 patients. Indications for local excision included favourable histology, patient choice and comorbidities. T1, T2 and T3 tumours accounted for 35.1%, 58.0% and 6.9% of cases, respectively. The most frequent local excision technique was transanal excision (77.7%). Adjuvant therapy included long-course chemoradiation or radiotherapy. Median follow-up was 51 months (range 1-165). The pooled local recurrence was 5.8% (95% CI 3.0-9.5) for pT1, 13.8% (95% CI 10.1-17.9) for pT2 and 33.7% (95% CI 19.2-50.1) for pT3 tumours. The overall median disease-free survival was 88% (range 50%-100%) with a pooled overall morbidity of 15.1% (95% CI 11.0-18.7). CONCLUSIONS: This area remains highly relevant to modern clinical practice. The data suggest that local excision followed by adjuvant therapy can achieve acceptable long-term outcomes in high-risk pT1 tumours, but not in T2 tumours and above in whom radical surgery should be offered.
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Adenocarcinoma/terapia , Quimioterapia Adyuvante/mortalidad , Proctectomía/mortalidad , Neoplasias del Recto/terapia , Recto/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Quimioterapia Adyuvante/métodos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Proctectomía/métodos , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Recto/patología , Resultado del TratamientoRESUMEN
Progesterone signaling and uterine function are crucial in terms of pregnancy establishment. To investigate how the uterine tissue and its secretion changes in relation to puberty, we sampled tissue and uterine fluid from six pre- and six post-pubertal Brahman heifers. Post-pubertal heifers were sampled in the luteal phase. Gene expression of the uterine tissue was investigated with RNA-sequencing, whereas the uterine fluid was used for protein profiling with mass spectrometry. A total of 4034 genes were differentially expressed (DE) at a nominal P-value of 0.05, and 26 genes were significantly DE after Bonferroni correction (P < 3.1 × 10-6 ). We also identified 79 proteins (out of 230 proteins) that were DE (P < 1 × 10-5 ) in the uterine fluid. When we compared proteomics and transcriptome results, four DE proteins were identified as being encoded by DE genes: OVGP1, GRP, CAP1 and HBA. Except for CAP1, the other three had lower expression post-puberty. The function of these four genes hypothetically related to preparation of the uterus for a potential pregnancy is discussed in the context of puberty. All DE genes and proteins were also used in pathway and ontology enrichment analyses to investigate overall function. The DE genes were enriched for terms related to ribosomal activity. Transcription factors that were deemed key regulators of DE genes are also reported. Transcription factors ZNF567, ZNF775, RELA, PIAS2, LHX4, SOX2, MEF2C, ZNF354C, HMG20A, TCF7L2, ZNF420, HIC1, GTF3A and two novel genes had the highest regulatory impact factor scores. These data can help to understand how puberty influences uterine function.
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Bovinos/genética , Proteoma , Maduración Sexual/genética , Transcriptoma , Útero/fisiología , Animales , Bovinos/fisiología , Femenino , Fase Luteínica , Análisis de Secuencia de ARNRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Interventions intended to slow the emergence and spread of antibacterial resistance through enhanced antimicrobial stewardship will be more effective if informed by an accurate knowledge of current patterns of antibacterial consumption. For example, knowledge of the relative magnitude of community antibacterial consumption in relation to hospital antibacterial consumption within each nation or region should help guide decisions about the relative importance of community and hospital antimicrobial stewardship programmes. It is commonly stated that community antibacterial consumption comprises approximately 80% of total national antibacterial consumption. We aimed to determine this proportion across a large range of nations. METHODS: We measured community and hospital antibacterial consumption in New Zealand during 2015, from both reimbursement and purchase data, and compared the New Zealand data with those reported from a large range of other nations during similar time periods. RESULTS AND DISCUSSION: Community antibacterial consumption comprised approximately 85%-95% of total antibacterial consumption in all nations for which data were available, and in New Zealand comprised a higher proportion than in any other nation. The proportion of total antibacterial consumption comprised by community consumption was significantly higher in countries with relatively high levels of total antibacterial consumption than in countries with relatively low levels of total antibacterial consumption. WHAT IS NEW AND CONCLUSION: The high proportion of total antibacterial consumption comprised by community antibacterial consumption suggests devoting particular attention to improved community antimicrobial stewardship. These results suggest that improving antimicrobial stewardship in the community may provide greater overall benefits in combating antibacterial resistance than improving antimicrobial stewardship in hospitals.
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Antibacterianos/uso terapéutico , Utilización de Medicamentos/estadística & datos numéricos , Farmacorresistencia Bacteriana/efectos de los fármacos , Hospitales , Humanos , Nueva ZelandaRESUMEN
BACKGROUND: Complete tumour response (pCR) to neo-adjuvant chemo-radiotherapy for rectal cancer is associated with a reduction in local recurrence and improved disease-free and overall survival, but is achieved in only 20-30% of patients. Drug repurposing for anti-cancer treatments is gaining momentum, but the potential of such drugs as adjuncts, to increase tumour response to chemo-radiotherapy in rectal cancer, is only just beginning to be recognised. METHODS: A systematic literature search was conducted and all studies investigating the use of drugs to enhance response to neo-adjuvant radiation in rectal cancer were included. 2137 studies were identified and following review 12 studies were extracted for full text review, 9 studies were included in the final analysis. RESULTS: The use of statins or aspirin during neo-adjuvant therapy was associated with a significantly higher rate of tumour downstaging. Statins were identified as a significant predictor of pCR and aspirin users had a greater 5-year progression-free survival and overall survival. Metformin use was associated with a significantly higher overall and disease-free survival, in a subset of diabetic patients. CONCLUSIONS: Aspirin, metformin and statins are associated with increased downstaging of rectal tumours and thus may have a role as adjuncts to neoadjuvant treatment, highlighting a clear need for prospective randomised controlled trials to determine their true impact on tumour response and overall survival.
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Aspirina/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Metformina/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Quimioterapia Adyuvante , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Tolerancia a Radiación/efectos de los fármacos , Neoplasias del Recto/patología , Neoplasias del Recto/radioterapia , Factores de RiesgoRESUMEN
Fertility traits, such as heifer pregnancy, are economically important in cattle production systems, and are therefore, used in genetic selection programs. The aim of this study was to identify single nucleotide polymorphisms (SNPs) using RNA-sequencing (RNA-Seq) data from ovary, uterus, endometrium, pituitary gland, hypothalamus, liver, longissimus dorsi muscle, and adipose tissue in 62 candidate genes associated with heifer puberty in cattle. RNA-Seq reads were assembled to the bovine reference genome (UMD 3.1.1) and analyzed in five cattle breeds; Brangus, Brahman, Nellore, Angus, and Holstein. Two approaches used the Brangus data for SNP discovery 1) pooling all samples, and 2) within each individual sample. These approaches revealed 1157 SNPs. These were compared with those identified in the pooled samples of the other breeds. Overall, 172 SNPs within 13 genes (CPNE5, FAM19A4, FOXN4, KLF1, LOC777593, MGC157266, NEBL, NRXN3, PEPT-1, PPP3CA, SCG5, TSG101, and TSHR) were concordant in the five breeds. Using Ensembl's Variant Effector Predictor, we determined that 12% of SNPs were in exons (71% synonymous, 29% nonsynonymous), 1% were in untranslated regions (UTRs), 86% were in introns, and 1% were in intergenic regions. Since these SNPs were discovered in RNA, the variants were predicted to be within exons or UTRs. Overall, 160 novel transcripts in 42 candidate genes and five novel genes overlapping five candidate genes were observed. In conclusion, 1157 SNPs were identified in 62 candidate genes associated with puberty in Brangus cattle, of which, 172 were concordant in the five cattle breeds. Novel transcripts and genes were also identified.
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Pubertad/genética , Animales , Secuencia de Bases , Bovinos , Femenino , Fertilidad/genética , Genoma , Masculino , Polimorfismo de Nucleótido Simple , Embarazo , ARN/genética , Selección Genética , Análisis de Secuencia de ARN/métodos , Maduración SexualRESUMEN
Human reproductive patterns have been well studied, but the mechanisms by which physiology, ecology and existing kin interact to affect the life history need quantification. Here, we create a model to investigate how age-specific interbirth intervals adapt to environmental and intrinsic mortality, and how birth patterns can be shaped by competition and help between siblings. The model provides a flexible framework for studying the processes underlying human reproductive scheduling. We developed a state-based optimality model to determine age-dependent and family-dependent sets of reproductive strategies, including the state of the mother and her offspring. We parameterized the model with realistic mortality curves derived from five human populations. Overall, optimal birth intervals increase until the age of 30 after which they remain relatively constant until the end of the reproductive lifespan. Offspring helping each other does not have much effect on birth intervals. Increasing infant and senescent mortality in different populations decreases interbirth intervals. We show that sibling competition and infant mortality interact to lengthen interbirth intervals. In lower-mortality populations, intense sibling competition pushes births further apart. Varying the adult risk of mortality alone has no effect on birth intervals between populations; competition between offspring drives the differences in birth intervals only when infant mortality is low. These results are relevant to understanding the demographic transition, because our model predicts that sibling competition becomes an important determinant of optimal interbirth intervals only when mortality is low, as in post-transition societies. We do not predict that these effects alone can select for menopause.
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Intervalo entre Nacimientos , Conducta Competitiva/fisiología , Modelos Teóricos , Hermanos/psicología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Mortalidad Infantil , Recién Nacido , Edad Materna , Mortalidad Materna , Menopausia , Persona de Mediana Edad , Factores Socioeconómicos , Adulto JovenRESUMEN
AIM: Patient-reported outcome (PRO) measures (PROMs) are standard measures in the assessment of colorectal cancer (CRC) treatment, but the range and complexity of available PROMs may be hindering the synthesis of evidence. This systematic review aimed to: (i) summarize PROMs in studies of CRC surgery and (ii) categorize PRO content to inform the future development of an agreed minimum 'core' outcome set to be measured in all trials. METHOD: All PROMs were identified from a systematic review of prospective CRC surgical studies. The type and frequency of PROMs in each study were summarized, and the number of items documented. All items were extracted and independently categorized by content by two researchers into 'health domains', and discrepancies were discussed with a patient and expert. Domain popularity and the distribution of items were summarized. RESULTS: Fifty-eight different PROMs were identified from the 104 included studies. There were 23 generic, four cancer-specific, 11 disease-specific and 16 symptom-specific questionnaires, and three ad hoc measures. The most frequently used PROM was the EORTC QLQ-C30 (50 studies), and most PROMs (n = 40, 69%) were used in only one study. Detailed examination of the 50 available measures identified 917 items, which were categorized into 51 domains. The domains comprising the most items were 'anxiety' (n = 85, 9.2%), 'fatigue' (n = 67, 7.3%) and 'physical function' (n = 63, 6.9%). No domains were included in all PROMs. CONCLUSION: There is major heterogeneity of PRO measurement and a wide variation in content assessed in the PROMs available for CRC. A core outcome set will improve PRO outcome measurement and reporting in CRC trials.
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Neoplasias Colorrectales/cirugía , Cirugía Colorrectal/métodos , Evaluación del Resultado de la Atención al Paciente , Autoinforme , Encuestas y Cuestionarios , HumanosRESUMEN
Our aim was to describe the epidemiology and incidence of community-onset invasive S. aureus disease in children presenting to our hospital, and to compare the clonal complexes and virulence genes of S. aureus strains causing invasive and non-invasive disease. The virulence gene repertoire of invasive disease isolates was characterized using DNA microarray and compared with the virulence gene repertoire of non-invasive S. aureus isolates. Over the study period, 163 children had an invasive S. aureus infection. There was no difference in the distribution of clonal complexes or in the prevalence of genes encoding virulence factors between invasive and non-invasive isolates. Future research should include a strong focus on identifying the host and environmental factors that, along with organism virulence factors, are contributing to the patterns of invasive S. aureus disease observed in New Zealand.
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Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/patología , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/patología , Staphylococcus aureus/clasificación , Staphylococcus aureus/genética , Adolescente , Niño , Preescolar , Análisis por Conglomerados , Infecciones Comunitarias Adquiridas/microbiología , Estudios Transversales , Genotipo , Humanos , Incidencia , Lactante , Recién Nacido , Análisis por Micromatrices , Epidemiología Molecular , Tipificación Molecular , Nueva Zelanda/epidemiología , Estudios Retrospectivos , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/aislamiento & purificación , Factores de Virulencia/genéticaRESUMEN
AIM: Evaluation of surgery for colorectal cancer (CRC) is necessary to inform clinical decision-making and healthcare policy. The standards of outcome reporting after CRC surgery have not previously been considered. METHOD: Systematic literature searches identified randomized and nonrandomized prospective studies reporting clinical outcomes of CRC surgery. Outcomes were listed verbatim, categorized into broad groups (outcome domains) and examined for a definition (an appropriate textual explanation or a supporting citation). Outcome reporting was considered inconsistent if results of the outcome specified in the methods were not reported. Outcome reporting was compared between randomized and nonrandomized studies. RESULTS: Of 5644 abstracts, 194 articles (34 randomized and 160 nonrandomized studies) were included reporting 766 different clinical outcomes, categorized into seven domains. A mean of 14 ± 8 individual outcomes were reported per study. 'Anastomotic leak', 'overall survival' and 'wound infection' were the three most frequently reported outcomes in 72, 60 and 44 (37.1%, 30.9% and 22.7%) studies, respectively, and no single outcome was reported in every publication. Outcome definitions were significantly more often provided in randomized studies than in nonrandomized studies (19.0% vs 14.9%, P = 0.015). One-hundred and twenty-seven (65.5%) papers reported results of all outcomes specified in the methods (randomized studies, n = 21, 61.5%; nonrandomized studies, n = 106, 66.2%; P = 0.617). CONCLUSION: Outcome reporting in CRC surgery lacks consistency and method. Improved standards of outcome measurement are recommended to permit data synthesis and transparent cross-study comparisons.
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Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Evaluación de Procesos y Resultados en Atención de Salud , Informe de Investigación/normas , Neoplasias Colorrectales/mortalidad , Humanos , Recurrencia Local de Neoplasia , Neoplasia Residual , Complicaciones PosoperatoriasRESUMEN
Geographic patterns of genetic variation, including variation at drug metabolizing enzyme (DME) loci and drug targets, indicate that geographic structuring of inter-individual variation in drug response may occur frequently. This raises two questions: how to represent human population genetic structure in the evaluation of drug safety and efficacy, and how to relate this structure to drug response. We address these by (i) inferring the genetic structure present in a heterogeneous sample and (ii) comparing the distribution of DME variants across the inferred genetic clusters of individuals. We find that commonly used ethnic labels are both insufficient and inaccurate representations of the inferred genetic clusters, and that drug-metabolizing profiles, defined by the distribution of DME variants, differ significantly among the clusters. We note, however, that the complexity of human demographic history means that there is no obvious natural clustering scheme, nor an obvious appropriate degree of resolution. Our comparison of drug-metabolizing profiles across the inferred clusters establishes a framework for assessing the appropriate level of resolution in relating genetic structure to drug response.
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Enzimas/genética , Variación Genética/genética , Preparaciones Farmacéuticas/metabolismo , Farmacogenética , Distribución de Chi-Cuadrado , Cromosomas Humanos Par 1/genética , Análisis por Conglomerados , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Enzimas/metabolismo , Etnicidad/genética , Frecuencia de los Genes/genética , Genotipo , Humanos , Masculino , Repeticiones de Microsatélite/genética , Herencia Multifactorial/genética , Oxidación-Reducción , Polimorfismo de Nucleótido Simple/genética , Grupos Raciales/genética , Programas Informáticos , Cromosoma X/genéticaRESUMEN
Schizophrenia is a common disorder characterized by psychotic symptoms; diagnostic criteria have been established. Family, twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (heritability is approximately 71%; ref. 2), however, little is known about the aetiology of schizophrenia. Clinical and family studies suggest aetiological heterogeneity. Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated with susceptibility to schizophrenia, and collaborations provided some support for regions on chromosomes 8 and 22 (refs 9-13). We present here a genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite markers on 54 multiplex pedigrees. Non-parametric linkage (NPL) analysis provided significant evidence for an SSL on chromosome 13q32 (NPL score=4.18; P=0.00002), and suggestive evidence for another SSL on chromosome 8p21-22 (NPL=3.64; P=0.0001). Parametric linkage analysis provided additional support for these SSL. Linkage evidence at chromosome 8 is weaker than that at chromosome 13, so it is more probable that chromosome 8 may be a false positive linkage. Additional putative SSL were noted on chromosomes 14q13 (NPL=2.57; P=0.005), 7q11 (NPL=2.50, P=0.007) and 22q11 (NPL=2.42, P=0.009). Verification of suggestive SSL on chromosomes 13q and 8p was attempted in a follow-up sample of 51 multiplex pedigrees. This analysis confirmed the SSL in 13q14-q33 (NPL=2.36, P=0.007) and supported the SSL in 8p22-p21 (NPL=1.95, P=0.023).
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Cromosomas Humanos Par 13 , Cromosomas Humanos Par 8 , Esquizofrenia/genética , Adulto , Susceptibilidad a Enfermedades , Femenino , Genes Dominantes , Ligamiento Genético , Humanos , Escala de Lod , Masculino , Repeticiones de Microsatélite , Modelos GenéticosRESUMEN
Woolly mammoths, Mammuthus primigenius, are arguably the most iconic of the extinct Pleistocene megafauna, and an abundance of large permafrost-embedded bone and ivory material (Fig. 1) means they were also among the first to yield credible DNA sequences (Hagelberg et al. 1994; Hoss et al. 1994). Despite mammoth remains being numerous throughout northern Eurasia and North America, both the earliest and most recent fossils are found in northeast Siberia, with the last known population being confined to Wrangel Island in the Arctic Ocean from around 10,000 years ago until their extinction around 4,000 years ago. The extent to which these Holocene mammoths were descended from the Pleistocene populations of Wrangel Island and the demographic nature of their terminal decline have, until now, remained something of a mystery. In this issue of Molecular Ecology, Nyström et al. (2012) report the first use of autosomal variation to track the decline of the last mammoths and, in doing so, take a significant step towards resolving these questions. The authors genotyped four microsatellite loci in 59 Pleistocene and Holocene mammoths from Wrangel Island and Chukotka in mainland northeastern Siberia and showed that while the Pleistocene-to-Holocene transition is associated with a significant reduction in genetic diversity, subsequent levels of variation remain constant until extinction. Such a pattern is somewhat surprising as it indicates that while the last mammoths were confined to only a few Arctic islands, their final extinction on Wrangel Island was not a gradual process resulting from loss of genetic diversity/inbreeding. Instead, it seems they maintained a viable effective population size of around 500 until near their presumably rapid extinction. While the ultimate agent of mammoth extinction remains unknown, the work of Nyström et al. (2012). suggests that we should be looking for something sudden, like a rapid change in climate/ecology or perhaps the arrival of humans.
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Evolución Molecular , Variación Genética , Genotipo , Mamuts/genética , Repeticiones de Microsatélite , AnimalesRESUMEN
AIM: An improvement in oncological outcome has been reported following an extralevator approach to abdominoperineal excision (ELAPE) for low rectal carcinoma. A larger perineal defect following ELAPE and the impact of neoadjuvant radiotherapy are sources of considerable morbidity for patients. We report an evidence-based systematic review of published data on the outcome of perineal reconstruction following ELAPE for low rectal carcinoma, comparing the use of tissue flap and biological mesh techniques. METHOD: A literature search was performed of electronic databases including the Medline, Embase and Scopus databases (1995-2011). Studies describing outcomes relating to the perineum following ELAPE were included for review. RESULTS: Eleven small cohort studies reported the outcome relating to the perineum following ELAPE. Pooled-analysis of 255 combined patients undergoing flap repair and 85 undergoing biological mesh repair showed no significant difference in the rates of perineal wound complications or perineal hernia formation. CONCLUSION: There is little information on the optimal technique of perineal wound closure following ELAPE. With the limited data available, there was no significant difference in complication rates between biological mesh and flap repair. There is a need for high-quality prospective trials to compare methods of reconstruction to determine the long-term results, quality of life and function.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Perineo/cirugía , Procedimientos de Cirugía Plástica/métodos , Neoplasias del Recto/cirugía , Bioprótesis , Humanos , Colgajos Quirúrgicos , Mallas Quirúrgicas , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
OBJECTIVES: The benefits of physical exercise for psychological aspects of quality of life (QoL) are well established in normally ageing adults, yet potential benefits for people with Parkinson's disease (PD) have received limited attention. This study evaluated the benefits of exercise for cognitive functioning, mood and disease-specific QoL for people with PD. METHODS: Twenty-eight individuals with PD were allocated to an exercise intervention program (EIP, n = 15) or control group (n = 13). The EIP group undertook a programme of progressive anabolic and aerobic exercise twice weekly for 12 weeks. The control group maintained their usual lifestyle. RESULTS: Exercise was shown to have selective benefits for cognitive functioning by improving frontal lobe based executive function. No significant effects were demonstrated for mood or disease-specific QoL. CONCLUSIONS: These results are consistent with previous research demonstrating selective benefits of exercise for executive function among normal ageing adults and PD.
Asunto(s)
Terapia por Ejercicio/métodos , Ejercicio Físico , Enfermedad de Parkinson , Calidad de Vida , Actividades Cotidianas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Enfermedad de Parkinson/rehabilitación , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
OBJECTIVE: This study investigated the predictive value of various coping processes for the psychological and disease specific aspects of health-related quality of life (HRQoL) in Parkinson's disease (PD). METHOD: Cross-sectional study of 85 participants with PD using the Ways of Coping Questionnaire (WCQ), Depression, Anxiety, and Stress Scale (DASS-21), quality of life (PDQ-39), and socio-demographic and clinical variables. RESULTS: Greater use of planful problem solving coping was found to be significantly associated with better HRQoL in relation to cognitive impairment, communication and bodily discomfort. In addition to greater disease duration, greater use of escape-avoidance coping processes were identified as significant predictors of poorer HRQoL outcomes in the domains of mood and emotional well-being. CONCLUSION: Psychological interventions such as mindfulness training, aimed at reducing the use of escape-avoidance copying, may help to improve HRQoL in PD.