RESUMO
The Wald test is routinely used in case-control studies to test for association between a covariate and disease. However, when the evidence for association is high, the Wald test tends to inflate small P values as a result of the Hauck-Donner effect (HDE). Here, we investigate the HDE in the context of genetic burden, both with and without additional covariates. First, we examine the burden-based P values in the absence of association using whole-exome sequence data from 1000 Genomes Project reference samples (n = 54) and selected preterm infants with neonatal complications (n = 74). Our careful analysis of the burden-based P values shows that the HDE is present and that the cause of the HDE in this setting is likely a natural extension of the well-known cause of the HDE in 2 × 2 contingency tables. Second, in a reanalysis of real data, we find that the permutation test provides increased power over the Wald, Firth, and likelihood ratio tests, which agrees with our intuition since the permutation test is valid for any sample size and since it does not suffer from the HDE. Therefore, we propose a powerful and computationally efficient permutation-based approach for the analysis and reanalysis of small case-control association studies.
Assuntos
Recém-Nascido Prematuro , Estudos de Casos e Controles , Simulação por Computador , Humanos , Recém-Nascido , Funções Verossimilhança , Tamanho da AmostraRESUMO
As whole-genome data become available for increasing numbers of individuals across diverse populations, the list of genomic variants of unknown significance (VOUS) continues to grow. One powerful tool in VOUS interpretation is determining whether an allele is too common to be considered pathogenic. As genetic and epidemiological parameters vary across disease models, so too does the pathogenic allele frequency threshold for each disease gene. One threshold-setting approach is the maximum credible allele frequency (MCAF) method. However, estimating some of the input values MCAF requires, especially those involving heterogeneity, can present nontrivial statistical challenges. Here, we introduce FREQMAX, our alternative approach for determining allele frequency thresholds in carrier screening. FREQMAX makes efficient use of the data available for well-studied traits and exhibits flexibility for traits where information may be less complete. For cystic fibrosis, more alleles are excluded as benign by FREQMAX than by MCAF. For less-comprehensively characterized traits like ciliary dyskinesia and Smith-Lemli-Opitz syndrome, FREQMAX is able to set the allele frequency threshold without requiring a priori estimates of maximum genetic and allelic contributions. Furthermore, though we describe FREQMAX in the context of carrier screening, its classical population genetics framework also provides context for adaptation to other trait models.
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Frequência do Gene/genética , Testes Genéticos , Software , Alelos , Transtornos da Motilidade Ciliar/genética , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Heterozigoto , Humanos , Síndrome de Smith-Lemli-Opitz/genéticaRESUMO
BACKGROUND: Preterm birth is the leading cause of mortality and morbidity in young children, with over a million deaths per year worldwide arising from neonatal complications (NCs). NCs are moderately heritable although the genetic causes are largely unknown. Therefore, we investigated the impact of accumulated genetic variation (burden) on NCs in non-Hispanic White (NHW) and non-Hispanic Black (NHB) preterm infants. METHODS: We sequenced 182 exomes from infants with gestational ages from 26 to 31 weeks. These infants were cared for in the same time period and hospital environment. Eighty-one preterm infants did not develop NCs, whereas 101 developed at least one severe complication. We measured the effect of burden at the single-gene and exome-wide levels and derived a polygenic risk score (PRS) from the top 10 genes to predict NCs. RESULTS: Burden across the exome was associated with NCs in NHW (p = 0.05) preterm infants suggesting that multiple genes influence susceptibility. In a post hoc analysis, we find that PRS alone predicts NCs (AUC = 0.67) and that PRS is uncorrelated with GA ([Formula: see text] = 0.05; p = 0.53). When PRS and GA at birth are combined, the AUC is 0.87. CONCLUSIONS: Our results support the hypothesis that genetic burden influences NCs in NHW preterm infants.
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Exoma , Predisposição Genética para Doença , Variação Genética , Doenças do Recém-Nascido/genética , Recém-Nascido Prematuro , Negro ou Afro-Americano , Alelos , Área Sob a Curva , Biomarcadores/metabolismo , Pré-Escolar , DNA/metabolismo , Feminino , Idade Gestacional , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Projetos Piloto , Nascimento Prematuro , Fatores de Risco , Populações Vulneráveis , População BrancaRESUMO
OBJECTIVE: Genetic generalized epilepsy (GGE) consists of epileptic syndromes with overlapping symptoms and is considered to be largely genetic. Previous cosegregation and association studies have pointed to malic enzyme 2 (ME2) as a candidate susceptibility gene for adolescent-onset GGE. In this article, we present new evidence supporting ME2's involvement in GGE. METHODS: To definitively test ME2's influence on GGE, we used 3 different approaches. First, we compared a newly recruited GGE cohort with an ethnically matched reference sample from 1000 Genomes Project, using an efficient test of association (POPFAM+). Second, we used POPFAM+ to reanalyze a previously collected data set, wherein the original controls were replaced with ethnically matched reference samples to minimize the confounding effect of population stratification. Third, in a post hoc analysis of expression data from healthy human prefrontal cortex, we identified single nucleotide polymorphisms (SNPs) influencing ME2 messenger RNA (mRNA) expression; and then we tested those same SNPs for association with GGE in a large case-control cohort. RESULTS: First, in the analysis of our newly recruited GGE Cohort, we found a strong association between an ME2 SNP and GGE (P = 0.0006 at rs608781). Second, in the reanalysis of previously collected data, we confirmed the Greenberg et al (2005) finding of a GGE-associated ME2 risk haplotype. Third, in the post hoc ME2 expression analysis, we found evidence for a possible link between GGE and ME2 gene expression in human brain. SIGNIFICANCE: Overall, our research, and the research of others, provides compelling evidence that ME2 influences susceptibility to adolescent-onset GGE.
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Epilepsia Generalizada/genética , Predisposição Genética para Doença/genética , Malato Desidrogenase/genética , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica/genética , Estudos de Associação Genética , Haplótipos/genética , Humanos , Malato Desidrogenase/fisiologia , Masculino , Polimorfismo de Nucleotídeo Único/genética , Adulto JovemRESUMO
OBJECTIVE: Juvenile myoclonic epilepsy (JME) is a common adolescent-onset genetic generalized epilepsy (GGE) syndrome. Multiple linkage and association studies have found that BRD2 influences the expression of JME. The BRD2-JME connection is further corroborated by our murine model; Brd2 haploinsufficiency produces characteristics that typify the clinical hallmarks of JME. Neither we, nor several large-scale studies of JME, found JME-related BRD2 coding mutations. Therefore, we investigated noncoding BRD2 regions, seeking the origin of BRD2's JME influence. BRD2's promoter harbors a JME-associated single nucleotide polymorphism (rs3918149) and a CpG (C-phosphate-G dinucleotides) island (CpG76), making it a potential "hotspot" for JME-associated epigenetic variants. Methylating promoter CpG sites causes gene silencing, often resulting in reduced gene expression. We tested for differences in DNA methylation at CpG76 in 3 different subgroups: (1) JME patients versus their unaffected family members, (2) JME versus patients with other forms of GGE, and (3) Caucasian versus non-Caucasian JME patients. METHODS: We used DNA pyrosequencing to analyze the methylation status of 10 BRD2 promoter CpG sites in lymphoblastoid cells from JME patients of Caucasian and non-Caucasian origin, unaffected family members, and also non-JME GGE patients. We also measured global methylation levels and DNA methyl transferase 1 (DNMT1) transcript expression in JME families by standard methods. RESULTS: CpG76 is highly methylated in JME patients compared to unaffected family members. In families with non-JME GGE, we found no relationship between promoter methylation and epilepsy. In non-Caucasian JME families, promoter methylation was mostly not associated with epilepsy. This makes the BRD2 promoter a JME-specific, ethnicity-specific, differentially methylated region. Global methylation was constant across groups. SIGNIFICANCE: BRD2 promoter methylation in JME, and the lack of methylation in unaffected relatives, in non-JME GGE patients, and in non-Caucasian JME, demonstrate that methylation specificity is a possible seizure susceptibility motif in JME risk and suggests JME therapeutics targeting BRD2.
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Metilação de DNA/genética , Epilepsias Mioclônicas/genética , Regiões Promotoras Genéticas/genética , Proteínas Serina-Treonina Quinases/genética , Criança , Feminino , Humanos , Masculino , Fatores de Transcrição , População Branca/genéticaRESUMO
BACKGROUND: Treating burns effectively requires accurately assessing the percentage of the total body surface area (%TBSA) affected by burns. Current methods for estimating %TBSA, such as Lund and Browder (L&B) tables, rely on historic body statistics. An increasingly obese population has been blamed for increasing errors in %TBSA estimates. However, this assumption has not been experimentally validated. We hypothesized that errors in %TBSA estimates using L&B were due to differences in the physical proportions of today's children compared with children in the early 1940s when the chart was developed and that these differences would appear as body mass index (BMI)-associated systematic errors in the L&B values versus actual body surface areas. MATERIALS AND METHODS: We measured the TBSA of human pediatric cadavers using computed tomography scans. Subjects ranged from 9 mo to 15 y in age. We chose outliers of the BMI distribution (from the 31st percentile at the low through the 99th percentile at the high). We examined surface area proportions corresponding to L&B regions. RESULTS: Measured regional proportions based on computed tomography scans were in reasonable agreement with L&B, even with subjects in the tails of the BMI range. The largest deviation was 3.4%, significantly less than the error seen in real-world %TBSA estimates. CONCLUSIONS: While today's population is more obese than those studied by L&B, their body region proportions scale surprisingly well. The primary error in %TBSA estimation is not due to changing physical proportions of today's children and may instead lie in the application of the L&B table.
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Superfície Corporal , Queimaduras/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Algoritmos , Criança , Pré-Escolar , Estudos de Coortes , Humanos , LactenteRESUMO
PURPOSE: To identify current challenges facing ophthalmic pharmaceutical start-ups in developing new products. METHODS: Surveys were distributed to the chief executive officer (CEO) or president of ophthalmic start-ups. RESULTS: The survey attracted 24 responses from 78 surveys distributed (31%). The CEOs stated that a lack of financial capital (n = 18, 75%), FDA regulations (n = 6, 25%), and failure to meet clinical endpoints (n = 6, 25%) were their greatest development hurdles. Risk aversion to medicines in early development (n = 18, 75%), mergers and acquisitions reducing corporate choice for licensing agreements (n = 7, 29%), the emergence of large pharmaceutical-based venture capital funding groups (n = 12, 50%), and the failure of many large pharmaceutical companies to develop their own medicines (n = 10, 42%) were noted as recent prominent trends affecting fundraising. CONCLUSION: The study suggests that development funding, regulatory burden, and meeting clinical endpoints are the greatest development challenges faced by ophthalmic start-up CEOs.
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Atitude do Pessoal de Saúde , Descoberta de Drogas/normas , Oftalmologia , Descoberta de Drogas/economia , Determinação de Ponto Final/normas , Organização do Financiamento , Humanos , Inquéritos e Questionários , Estados Unidos , United States Food and Drug Administration/normasRESUMO
To survey ophthalmologists regarding sources they trust when incorporating new medical knowledge into their practice. The survey was distributed primarily to US-based ophthalmologists. Questions were derived based on the lead author's research experience from congresses and discussions and from mentions in the medical literature. In total, 77 physicians completed the survey of 1886 sent (4% response rate). Regarding study design, physicians preferred a well-controlled, randomised, double-masked trial (99%) with multicentred investigational site across a wide geographical area (80%). Authorship of a research article was most desired from a well-known key opinion leader (KOL) (75%) or any KOL leader at a university (75%). The most selected journal type was a subspecialty publication (86%) and second a multispecialty high impact journal (77%). Study sponsorship was most desired from the NIH or other government agencies (71%) or a university (71%). Doctors preferred clinical opinions from an ophthalmic medical society (75%). For the source of new clinical data, physicians indicated an unsponsored peer-reviewed journal article (77%) or a lecture at a large ophthalmic congress (74%) as the preferred source. Ophthalmologists generally desire sponsors, study designs and opinions that appear free of bias on which to base their clinical practice decisions.
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Medicina Baseada em Evidências , Oftalmologistas , Projetos de Pesquisa/normas , Relatório de Pesquisa/normas , Autoria , Publicações Periódicas como Assunto , Apoio à Pesquisa como Assunto , Inquéritos e Questionários , ConfiançaRESUMO
The purpose of this study was to review four parameters (forgiveness, gratitude, hope and empathy) frequently noted when evaluating well-being. We reviewed clinical studies from 1966 to present. We included 63 articles. All four of the parameters were shown to generally improve an individual's well-being. These parameters demonstrated a positive influence within more specific societal issues including improvement in social relationships, delinquent behavior and physical health. These parameters were generally derived from training and religion. This study suggests that these parameters may improve either one of general well-being, pro-social and positive relational behavior and demonstrate positive health effects.
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Adaptação Psicológica , Empatia , Perdão , Felicidade , Esperança , Qualidade de Vida/psicologia , HumanosRESUMO
OBJECTIVE: Screening for specific coding mutations in the EFHC1 gene has been proposed as a means of assessing susceptibility to juvenile myoclonic epilepsy (JME). To clarify the role of these mutations, especially those reported to be highly penetrant, we sought to measure the frequency of exonic EFHC1 mutations across multiple population samples. METHODS: To find and test variants of large effect, we sequenced all EFHC1 exons in 23 JME and 23 non-JME idiopathic generalized epilepsy (IGE) Hispanic patients, and 60 matched controls. We also genotyped specific EFHC1 variants in IGE cases and controls from multiple ethnic backgrounds, including 17 African American IGE patients, with 24 matched controls, and 92 Caucasian JME patients with 103 matched controls. These variants are reported to be pathogenic, but are also found among unphenotyped individuals in public databases. All subjects were from the New York City metro area and all controls were required to have no family history of seizures. RESULTS: We found the reportedly pathogenic EFHC1 P77T-R221H (rs149055334-rs79761183) JME haplotype in one Hispanic control and in two African American controls. Public databases also show that the EFHC1 P77T-R221H JME haplotype is present in unphenotyped West African ancestry populations, and we show that it can be found at appreciable frequency in healthy individuals with no family history of epilepsy. We also found a novel splice-site mutation in a single Hispanic JME patient, the effect of which is unknown. SIGNIFICANCE: Our findings raise questions about the effect of reportedly pathogenic EFHC1 mutations on JME. One intriguing possibility is that some EFHC1 mutations may be pathogenic only when introduced into specific genetic backgrounds. By focusing on data from multiple populations, including the understudied Hispanic and Black/African American populations, our study highlights that for complex traits like JME, the body of evidence necessary to infer causality is high.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Epilepsia Generalizada/genética , Predisposição Genética para Doença , Mutação/genética , Epilepsia Mioclônica Juvenil/genética , Idade de Início , Genótipo , Humanos , Epilepsia Mioclônica Juvenil/diagnóstico , LinhagemRESUMO
AIM: To evaluate techniques used to reduce the placebo effect in prior well-controlled, single or double-masked placebo-controlled glaucoma trials. METHODS: This study was a retrospective, non-patient-based, observational review of phase I-III trials with a placebo arm for glaucoma medicines available after 1977. RESULTS: This study included 20 articles with 20 placebo control arms consisting of 458 patients evaluating 10 different glaucoma medications with 58 treatment arms. There was no statistical difference across the evaluated types of study designs to limit the placebo effect either for the morning trough or diurnal curve. The average reduction of the intraocular pressure in the placebo groups was 1.6 ± 1.5 mm Hg for the morning trough and 1.3 ± 1.3 mm Hg for the diurnal curve across all studies. CONCLUSION: The results of this study suggest that current design techniques described in the literature to limit the placebo effect appear ineffective compared to no additional techniques.
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Anti-Hipertensivos/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Glaucoma/tratamento farmacológico , Efeito Placebo , Método Duplo-Cego , Humanos , Pressão Intraocular/efeitos dos fármacos , Projetos de Pesquisa , Estudos Retrospectivos , Método Simples-Cego , Tonometria OcularRESUMO
AIMS: To describe the number, type and location of ophthalmic companies and their associated product areas and indications. METHODS: A retrospective, non-patient-based, observational review of ophthalmic pharmaceutical and device companies with a new product in development. Data was compiled by Internet searches. RESULTS: We identified 190 companies currently developing ophthalmic products: 134 (71%) were privately held and 56 (29%) publicly held, while 136 (72%) were in the United States and 53 (28%) were outside the United States. There were 436 total products of which 338 (78%) were pharmaceuticals and 98 (22%) devices. With pharmaceuticals we identified 46 separate indications with age-related macular degeneration (n = 75), glaucoma (n = 52) and dry eye (n = 46) as most common; anti-vascular endothelial growth factor, hormone therapy and anti-inflammatory products were also common classes. With devices there were 30 indications with glaucoma (n = 26), age-related macular degeneration (n = 19) and dry eye (n = 6) as most common; drug delivery, ocular implants and prostheses were less common classes. CONCLUSIONS: Ophthalmology as a specialty is benefited by a wide effort in new medicine and device development. However, a concentration of effort into relatively few indications suggests a potential lack of market analysis and possible difficulty for many companies in commercializing their product.
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Aprovação de Equipamentos , Indústria Farmacêutica , Oftalmopatias/terapia , Oftalmologia/organização & administração , Preparações Farmacêuticas , França , Israel , Estudos Retrospectivos , Suíça , Reino Unido , Estados UnidosRESUMO
OBJECTIVE: The aim of this study is to compare daily Pediatric Migraine Disability Assessment (PedMIDAS)-based scores for headaches occurring on school days vs non-school days and during the school year vs the summer holiday. BACKGROUND: The PedMIDAS is the only instrument validated to assess migraine disability among school-aged children. However, the PedMIDAS may underestimate disability during prolonged school holidays. METHODS: In a prospective cohort study, migraine patients aged 10-18 years completed a 90-day Internet-based headache diary. For each headache day, they answered PedMIDAS-based questions and rated their headache intensity (scale 1-10). PedMIDAS-based scores, headache intensity ratings, and relative headache frequencies were compared for school days vs non-school days and for the school year vs the summer holiday. RESULTS: Fifty-two patients completed 4680 diary entries comprising 984 headache days. The headache frequencies and intensity ratings did not differ between time periods. However, the mean headache disability scores (as measured from PedMIDAS-based questions) were significantly different for school days (0.85) compared to non-school days (0.45), P < .001, and for the school year (0.73) compared to the summer holiday (0.46), P < .016. CONCLUSION: Given similar headache intensities and frequencies, daily PedMIDAS-based scores significantly underestimate headache disability on non-school days. Accordingly, PedMIDAS scoring during the school year may not be comparable to assessments done during the summer holiday. These potential differences must be considered when using the instrument as an outcome measure for clinical trials.
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Avaliação da Deficiência , Férias e Feriados , Transtornos de Enxaqueca/epidemiologia , Instituições Acadêmicas , Adolescente , Criança , Feminino , Humanos , Masculino , Prontuários Médicos , EstudantesRESUMO
To assess the impact of community service on personal wellbeing in a mid-west church-based population. A prospective survey evaluating: self-reported community service, the perceived benefit of the service and its association to personal wellbeing. 309 participants were included of whom 92 % were employed full or part time, homemakers or students. Those who served in some capacity had better scores on five Wellbeing questions including: contentment, peace, joy, purpose and community acceptance (P < 0.02), but not better self-perceived mental or physical health (P > 0.05). People who served had a better combined Wellbeing score than those who could not serve (P = 0.03). A higher number of hours served/week was associated with better Global Wellbeing (P = 0.02). The greatest perceived benefit of service was related to enhancing wellbeing of others and the service organization itself (P < 0.0001). Church going adults, who are serving in some capacity in their church or community, may demonstrate heightened personal wellbeing compared to those who are not assisting others.
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Redes Comunitárias , Satisfação Pessoal , Voluntários/psicologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Espiritualidade , Inquéritos e Questionários , Adulto JovemRESUMO
Natural killer (NK) cells are currently in use as immunotherapeutic agents for cancer. Many different cytokines are used to generate NK cells including IL-2, IL-12, IL-15 and IL-18 in solution and membrane bound IL-21. These cytokines drive NK cell activation through the integration of STAT and NF-κB pathways, which overlap and synergize, making it challenging to predict optimal cytokine combinations. We integrated functional assays for NK cells cultured in a variety of cytokine combinations with feature selection and mechanistic regression models. Our regression model successfully predicts NK cell proliferation for different cytokine combinations and indicates synergy between STAT3 and NF-κB transcription factors. Use of IL-21 in solution in the priming, but not post-priming phase of NK cell culture resulted in optimal NK cell proliferation, without compromising cytotoxicity or IFN-γ secretion against hepatocellular carcinoma cell lines. Our work provides a mathematical framework for interrogating NK cell activation for cancer immunotherapy.
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PURPOSE: To evaluate methods which account for both eyes as a single, independent variable in glaucoma clinical trials. METHODS: A review of clinical trial articles published between January 1995 and April 2011 evaluating currently used topical glaucoma medications. RESULTS: This analysis included 17 articles with 36 treatment arms of which 14 were prostaglandins, 13 ß-blockers, 6 topical carbonic anhydrase inhibitors and 3 α-agonists. Twenty-four articles used average intraocular pressure (IOP) analysis, 12 used the highest IOP analysis and none utilized the randomized eye method. At untreated baseline, there was a difference in the IOP between average IOP and highest baseline IOP analyses at 8 a.m. (p = 0.001) and for the diurnal curve (p = 0.02) as well as specifically for ß-blockers (p = 0.002) at 8 a.m. and ß-blockers for the diurnal curve (p = 0.01). CONCLUSIONS: This study suggests that the highest IOP analysis method generally provides slightly higher IOPs at baseline than the average IOP analysis method.
Assuntos
Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Análise de Variância , Anti-Hipertensivos/uso terapêutico , Ensaios Clínicos como Assunto , Glaucoma/tratamento farmacológico , Humanos , Avaliação de Resultados em Cuidados de Saúde/métodosRESUMO
A major concern of resequencing studies is that the pathogenicity of most mutations is difficult to predict. To address this concern, linkage (i.e. co-segregation) analysis is often used to exclude neutral mutations and to better predict pathogenicity among the candidate mutations that remain. However, when linkage disequilibrium (LD) is present in the population but ignored in the analysis, unlinked regions with high LD can inflate the type 1 error and thousands of neutral mutations may be mistakenly included in a follow-up resequencing study, which could dramatically reduce the power to identify causal variants. To illustrate the need for concern, we simulated data on a sparsely spaced panel of single nucleotide polymorphisms (average spacing 1.27 cM) using an LD pattern estimated from real data. In our simulations, we find that the type 1 error of the maximum LOD can be as high as 14%. Therefore, to control the type 1 error of linkage tests we created Haplodrop - a fast and flexible simulation program that generates the haplotypes of founders with LD and then 'drops' these haplotypes with recombination to all non-founders in the pedigree. Haplodrop can be used to control the type 1 error of any linkage test, agrees well with existing software, accommodates arbitrary pedigree structures, and scales easily to the whole genome. Moreover, by correctly excluding mutations that lie in unlinked regions with high LD, Haplodrop should aid significantly in reducing the multiple testing burden of follow-up resequencing studies.
Assuntos
Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Ligação Genética , Genoma Humano , Haplótipos , Humanos , SoftwareRESUMO
The purpose was to evaluate faith-based studies within the medical literature to determine whether there are ways to help physicians understand how religion affects patients' lives and diseases. We reviewed articles that assessed the influence of religious practices on medicine as a primary or secondary variable in clinical practice. This review evaluated 49 articles and found that religious faith is important to many patients, particularly those with serious disease, and patients depend on it as a positive coping mechanism. The findings of this review can suggest that patients frequently practice religion and interact with God about their disease state. This spiritual interaction may benefit the patient by providing comfort, increasing knowledge about their disease, greater treatment adherence, and quality of life. The results of prayer on specific disease states appear inconsistent with cardiovascular disease but stronger in other disease states.
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Medicina Clínica , Relações Médico-Paciente , Religião e Medicina , Adaptação Psicológica , Doenças Cardiovasculares/psicologia , Doenças Cardiovasculares/terapia , Doença Crônica/psicologia , Dor Crônica/psicologia , Dor Crônica/terapia , Diabetes Mellitus/psicologia , Diabetes Mellitus/terapia , Oftalmopatias/psicologia , Oftalmopatias/terapia , Humanos , Neoplasias/psicologia , Neoplasias/terapia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Cooperação do Paciente/psicologia , Qualidade de Vida/psicologia , Autocuidado/psicologia , Espiritualidade , Resultado do TratamentoRESUMO
Neuroblastoma (NB) is a common type of cancer found mostly in infants and arising from the immature neural crest cells of the sympathetic nervous system. Using laser trapping (LT) technique, the present work contributes to advancing radiotherapy (RT), a leading treatment method for cancer. A single, 2-cells, 3-cells, 4-cells, and 5-cells were trapped using the high-intensity gradient infrared laser at 1064 nm and allowed to become ionized. In this work, a systematic study of Threshold Ionization Energy (TIE) and Threshold Radiation Dose (TRD) versus mass for both single and multi-cell ionization using laser trapping (LT) techniques on NB is presented. The results show that TIE increased as the mass of cells increased, meanwhile TRD decreased with the increase of cell mass. We observed an inverse correlation between TRD and cell mass. We demonstrate how to compute the maximum radiation dosage for cell death using the LT technique. Results show a possible blueprint for computing the TRD in vivo. The use of multiple cell ionization to determine radiation dosage along with better data accuracy concerning the tumor size and density will have profound implications for radiation dosimetry. The diminution in TRD becomes more significant in multiple cell ionization as we see in TRD vs the number of cells entering the trap. This is due to the chain effect generated by radiation and the absorption by water molecules at 1064 nm. This result provides us with better insight into the optimization of the therapeutic ratio.