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1.
Int J Mol Sci ; 23(4)2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35216360

RESUMO

Whole-genome sequencing (WGS) data present a readily available resource for mitochondrial genome (mitogenome) haplotypes that can be utilized for genetics research including population studies. However, the reconstruction of the mitogenome is complicated by nuclear mitochondrial DNA (mtDNA) segments (NUMTs) that co-align with the mtDNA sequences and mimic authentic heteroplasmy. Two minimum variant detection thresholds, 5% and 10%, were assessed for the ability to produce authentic mitogenome haplotypes from a previously generated WGS dataset. Variants associated with NUMTs were detected in the mtDNA alignments for 91 of 917 (~8%) Swedish samples when the 5% frequency threshold was applied. The 413 observed NUMT variants were predominantly detected in two regions (nps 12,612-13,105 and 16,390-16,527), which were consistent with previously documented NUMTs. The number of NUMT variants was reduced by ~97% (400) using a 10% frequency threshold. Furthermore, the 5% frequency data were inconsistent with a platinum-quality mitogenome dataset with respect to observed heteroplasmy. These analyses illustrate that a 10% variant detection threshold may be necessary to ensure the generation of reliable mitogenome haplotypes from WGS data resources.


Assuntos
DNA Mitocondrial/genética , Genoma Mitocondrial/genética , Haplótipos/genética , Mitocôndrias/genética , Núcleo Celular/genética , Humanos , Sequenciamento Completo do Genoma/métodos
2.
Electrophoresis ; 39(21): 2785-2797, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30151910

RESUMO

Nuclear mitochondrial DNA segments (NUMTs) have arisen because of the transposition of segments of the mitochondrial DNA genome (mitogenome) into the nuclear genome. When using a "mitotiling" strategy, NUMTs may be more readily amplified when targeting the entire mitogenome compared to the control region, as hundreds of primers are required for complete sequencing coverage. In samples with a high percentage of nuclear DNA copies per cell, such as whole blood, NUMT coenrichment may be exacerbated. The present study examined bioinformatic approaches for removing NUMTs and NUMT-associated variants (NAVs) from next-generation sequence data generated using two mitotiling kits (Precision ID and QIAseq). Across 16 samples with low mtDNA copy number, NUMT coenrichment produced 890 NAVs with >5% variant frequency. The use of the consensus sequence to eliminate NUMT reads proved to be effective for QIAseq data, and resulted in >85% NAV removal in Precision ID data. This method was bolstered by NAV filtering in Precision ID analysis. Alternative high stringency mapping to the revised Cambridge Reference Sequence (rCRS) and the human genome reference GRCh38 for the QIAseq data caused a reduction in mitogenome coverage without complete NUMT removal. These bioinformatic solutions facilitate mitotiling sequence data analysis for low-level variant detection.


Assuntos
Núcleo Celular/genética , DNA Mitocondrial/genética , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , DNA/sangue , DNA/genética , Impressões Digitais de DNA/métodos , Biblioteca Gênica , Genoma Mitocondrial , Humanos
3.
Foot Ankle Spec ; 16(2): 135-144, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34176315

RESUMO

BACKGROUND: Ankle fractures in the elderly are an increasing problem, with poor outcomes reported. Operative options for patients with suspected osteoporosis and needing to bear weight to ambulate can include hindfoot intramedullary nail (IMN) or fibula pro-tibia fixation (FPT). FPT involves passing 2 or more screws through a lateral fibula plate, crossing the fibular into the tibia, with 1 or more screws proximal to the incisura. We compared the outcomes of these 2 techniques. METHOD: A retrospective review identified 68 patients aged over 60 years with unstable ankle fractures, treated with IMN or FPT. Primary outcome was surgical reoperation/revision rate, secondary outcomes included complications, length of stay, and functional status. Results: There were no significant differences in demographics between IMN and FPT. Revision rates were higher in IMN compared with FPT (P < .0001). IMN patients postoperatively had longer hospital stays (P = .02), longer follow-up times (P = .008), and higher rates of delayed wound healing (P = .03) and nonunion (P = .001). Multivariate analysis identified fixation and age to affect revision rates. CONCLUSION: Outcomes were worse in the IMN group compared with FPT. We believe both techniques have a role in the management of elderly ankle fractures, but patient selection is key. We suggest that FPT should be the first-choice technique when soft tissues permit. LEVELS OF EVIDENCE: Level III.


Assuntos
Fraturas do Tornozelo , Fixação Intramedular de Fraturas , Fraturas da Tíbia , Idoso , Humanos , Pessoa de Meia-Idade , Fixação Intramedular de Fraturas/métodos , Tíbia/cirurgia , Fraturas do Tornozelo/cirurgia , Fíbula/cirurgia , Tornozelo , Fraturas da Tíbia/cirurgia , Resultado do Tratamento , Consolidação da Fratura , Estudos Retrospectivos , Pinos Ortopédicos
4.
Chem Mater ; 35(13): 5135-5149, 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37456594

RESUMO

Spinels of the general formula Li2-δM2O4 are an essential class of cathode materials for Li-ion batteries, and their optimization in terms of electrode potential, accessible capacity, and charge/discharge kinetics relies on an accurate understanding of the underlying solid-state mass and charge transport processes. In this work, we report a comprehensive impedance study of sputter-deposited epitaxial Li2-δMn2O4 thin films as a function of state-of-charge for almost the entire tetrahedral-site regime (1 ≤ δ ≤ 1.9) and provide a complete set of electrochemical properties, consisting of the charge-transfer resistance, ionic conductivity, volume-specific chemical capacitance, and chemical diffusivity. The obtained properties vary by up to three orders of magnitude and provide essential insights into the point defect concentration dependences of the overall electrode potential. We introduce a defect chemical model based on simple concentration dependences of the Li chemical potential, considering the tetrahedral and octahedral lattice site restrictions defined by the spinel crystal structure. The proposed model is in excellent qualitative and quantitative agreement with the experimental data, excluding the two-phase regime around 4.15 V. It can easily be adapted for other transition metal stoichiometries and doping states and is thus applicable to the defect chemical analysis of all spinel-type cathode materials.

5.
Genes (Basel) ; 14(11)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-38002932

RESUMO

The development of complete mitochondrial genome (mitogenome) reference data for inclusion in publicly available population databases is currently underway, and the generation of more high-quality mitogenomes will only enhance the statistical power of this forensically useful locus. To characterize mitogenome variation in Sweden, the mitochondrial DNA (mtDNA) reads from the SweGen whole genome sequencing (WGS) dataset were analyzed. To overcome the interference from low-frequency nuclear mtDNA segments (NUMTs), a 10% variant frequency threshold was applied for the analysis. In total, 934 forensic-quality mitogenome haplotypes were characterized. Almost 45% of the SweGen haplotypes belonged to haplogroup H. Nearly all mitogenome haplotypes (99.1%) were assigned to European haplogroups, which was expected based on previous mtDNA studies of the Swedish population. There were signature northern Swedish and Finnish haplogroups observed in the dataset (e.g., U5b1, W1a), consistent with the nuclear DNA analyses of the SweGen data. The complete mitogenome analysis resulted in high haplotype diversity (0.9996) with a random match probability of 0.15%. Overall, the SweGen mitogenomes provide a large mtDNA reference dataset for the Swedish population and also contribute to the effort to estimate global mitogenome haplotype frequencies.


Assuntos
DNA Mitocondrial , Genoma Mitocondrial , Suécia , Análise de Sequência de DNA , DNA Mitocondrial/genética , Genoma Mitocondrial/genética , Mitocôndrias/genética
6.
Chem Mater ; 34(23): 10548-10560, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36530944

RESUMO

Lithium insertion materials are an essential class of mixed ionic and electronic conductors, and their electrochemical properties depend on the resistive and capacitive interplay of ions and electrons. However, complete sets of the corresponding elementary material parameters, that is, composition-dependent ionic and electronic conductivity, chemical capacitance, and charge-transfer resistance, are rarely reported for lithium-ion battery electrode materials. Moreover, the interpretation of these properties from a defect chemical point of view is not very common. In this work, the impedance of sputtered Li1-δCoO2 thin films is analyzed to extract the fundamental electrochemical properties as a function of state-of-charge (SOC). Within the accessible SOC range, the charge transfer resistance and ionic conductivity vary by more than 1 order of magnitude. The chemical capacitance determined from impedance spectra agrees excellently with the differential capacitance from charge/discharge curves, and, in the dilute regime, even matches the absolute values predicted by defect thermodynamics. The evolution of lithium diffusivity along the charge curve is deconvoluted into the separate contributions of ionic conductivity and chemical capacitance. Finally, we apply the principles of defect chemistry to evaluate the observed trends in terms of lithium activity and point defect concentrations and provide a tentative defect model that is consistent with our results. The consistency of impedance measurements, cycling data, and thermodynamic theory highlights the key role of the chemical capacitance as a powerful material descriptor and emphasizes the relevance of defect chemical concepts for all lithium insertion electrode materials.

7.
Mater Adv ; 3(23): 8760-8770, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36544614

RESUMO

Li7La3Zr2O12 (LLZO) garnets are highly attractive to be used as solid electrolyte in solid-state Li batteries. However, LLZO suffers from chemical interaction with air and humidity, causing Li+/H+ exchange with detrimental implication on its performance, processing and scalability. To better understand the kinetics of the detrimental Li+/H+ exchange and its dependence on microstructural features, accelerated Li+/H+ exchange experiments were performed on single crystalline and polycrystalline LLZO, exposed for 80 minutes to 80 °C hot water. The resulting chemical changes were quantified by analytical methods, i.e. inductively coupled plasma optical emission spectroscopy (ICP-OES) and laser induced breakdown spectroscopy (LIBS). From the time dependence of the Li+ enrichment in the water, measured by ICP-OES, a bulk interdiffusion coefficient of Li+/H+ could be determined (7 × 10-17 m2 s-1 at 80 °C). Depth dependent concentrations were obtained from the LIBS data for both ions after establishing a calibration method enabling not only Li+ but also H+ quantification in the solid electrolyte. Short interdiffusion lengths in the 1 µm range are found for the single crystalline Ga:LLZO, in accordance with the measured bulk diffusion coefficient. In polycrystalline Ta:LLZO, however, very long diffusion tails in the 20 µm range and ion exchange fractions up to about 70% are observed. Those are attributed to fast ion interdiffusion along grain boundaries. The severe compositional changes also strongly affect the electrical properties measured by impedance spectroscopy. This study highlights that microstructural effects may be decisive for the Li+/H+ ion exchange kinetics of LLZO.

8.
Bone Joint J ; 103-B(4): 696-703, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33789488

RESUMO

AIMS: We report the medium-term outcomes of a consecutive series of 118 Zenith total ankle arthroplasties (TAAs) from a single, non-designer centre. METHODS: Between December 2010 and May 2016, 118 consecutive Zenith prostheses were implanted in 114 patients. Demographic, clinical, and patient-reported outcome measures (PROMs) data were collected. The endpoint of the study was failure of the implant requiring revision of one or all of the components. Kaplan-Meier survival curves were generated with 95% confidence intervals (CIs) and the rate of failure calculated for each year. RESULTS: Eight patients (ten ankles) died during follow-up, but none required revision. Of the surviving 106 patients (108 ankles: rheumatoid arthritis (RA), n = 15; osteoarthritis (OA), n = 93), 38 were women and 68 were men, with a mean age of 68.2 years (48 to 86) at the time of surgery. Mean follow-up was 5.1 years (2.1 to 9.0). A total of ten implants failed (8.5%), thus requiring revision. The implant survival at seven years, using revision as an endpoint, was 88.2% (95% CI 100% to 72.9%). There was a mean improvement in Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ) from 85.0 to 32.8 and visual analogue scale (VAS) scores from 7.0 to 3.2, and overall satisfaction was 89%. The three commonest complications were malleolar fracture (14.4%, n = 17), wound healing (13.6%, n = 16), and superficial infection (12.7%, n = 15). The commonest reason for revision was aseptic loosening. No patients in our study were revised for deep infection. CONCLUSION: Our results show that Zenith survival rates are comparable with those in the literature for other implants and in the National Joint Registry (NJR). Overall patient satisfaction was high as were functional outcomes. However, the data highlight potential complications associated with this surgery. The authors believe that these figures support ankle arthroplasty as an option in the treatment of ankle arthritis. Cite this article: Bone Joint J 2021;103-B(4):696-703.


Assuntos
Artroplastia de Substituição do Tornozelo/métodos , Medidas de Resultados Relatados pelo Paciente , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/cirurgia , Feminino , Humanos , Prótese Articular , Masculino , Pessoa de Meia-Idade , Osteoartrite/cirurgia , Complicações Pós-Operatórias/epidemiologia , Falha de Prótese , Reoperação/estatística & dados numéricos , Reino Unido/epidemiologia
9.
J Mater Chem A Mater ; 9(27): 15226-15237, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34354833

RESUMO

Cubic Li7La3Zr2O12 (LLZO) garnets are among the most promising solid electrolytes for solid-state batteries with the potential to exceed conventional battery concepts in terms of energy density and safety. The electrochemical stability of LLZO is crucial for its application, however, controversial reports in the literature show that it is still an unsettled matter. Here, we investigate the electrochemical stability of LLZO single crystals by applying electric field stress via macro- and microscopic ionically blocking Au electrodes in ambient air. Induced material changes are subsequently probed using various locally resolved analysis techniques, including microelectrode electrochemical impedance spectroscopy (EIS), laser induced breakdown spectroscopy (LIBS), laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), and microfocus X-ray diffraction (XRD). Our experiments indicate that LLZO decomposes at 4.1-4.3 V vs. Li+/Li, leading to the formation of Li-poor phases like La2Zr2O7 beneath the positively polarized electrode. The reaction is still on-going even after several days of polarization, indicating that no blocking interfacial layer is formed. The decomposition can be observed at elevated as well as room temperature and suggests that LLZO is truly not compatible with high voltage cathode materials.

10.
Bone Joint J ; 102-B(2): 220-226, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32009425

RESUMO

AIMS: Arthroplasty for end-stage hallux rigidus (HR) is controversial. Arthrodesis remains the gold standard for surgical treatment, although is not without its complications, with rates of up to 10% for nonunion, 14% for reoperation and 10% for metatarsalgia. The aim of this study was to analyze the outcome of a double-stemmed silastic implant (Wright-Medical, Memphis, Tennessee, USA) for patients with end-stage HR. METHODS: We conducted a retrospective review of 108 consecutive implants in 76 patients, between January 2005 and December 2016, with a minimum follow-up of two years. The mean age of the patients at the time of surgery was 61.6 years (42 to 84). There were 104 females and four males. Clinical, radiological, patient reported outcome measures (PROMS) data, a visual analogue score (VAS) for pain, and satisfaction scores were collected. RESULTS: The survivorship at a mean follow-up of 5.3 years (2.1 to 14.1) was 97.2%. The mean Manchester Oxford Foot and Ankle Questionnaire (MOXFQ) scores improved from 78.1 to 11.0, and VAS scores for pain from 7/10 to 1.3/10. The rate of satisfaction was 90.6%. Three implants (2.8%) required revision; one for infection, one-month postoperatively, and two for stem breakage at 10.4 and 13.3 years postoperatively. There was a 1.9% reoperation rate other than revision, 23.1% of patients developed a minor complication, and 21.1% of patients had non-progressive and asymptomatic cysts on radiological review. CONCLUSION: We report a 97.2% survivorship at a mean follow-up of 5.3 years with this implant. We did not find progressive osteolysis, as has been previously reported. These results suggest that this double-stemmed silastic implant provides a predictable and reliable alternative with comparable outcomes to arthrodesis for the treatment of end-stage HR. Cite this article: Bone Joint J 2020;102-B(2):220-226.


Assuntos
Artroplastia de Substituição/métodos , Hallux Rigidus/cirurgia , Prótese Articular , Articulação Metatarsofalângica/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Materiais Biocompatíveis , Dimetilpolisiloxanos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Genes (Basel) ; 11(10)2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32998193

RESUMO

Given the enhanced discriminatory power of the mitochondrial DNA (mtDNA) genome (mitogenome) over the commonly sequenced control region (CR) portion, the scientific merit of mitogenome sequencing is generally accepted. However, many laboratories remain beholden to CR sequencing due to privacy policies and legal requirements restricting the use of disease information or coding region (codR) information. In this report, we present an approach to obviate the reporting of sensitive codR data in forensic haplotypes. We consulted the MitoMap database to identify 92 mtDNA codR variants with confirmed pathogenicity. We determined the frequencies of these pathogenic variants in literature-quality and forensic-quality databases to be very low, at 1.2% and 0.36%, respectively. The observed effect of pathogenic variant filtering on random match statistics in 2488 forensic-quality mitogenome haplotypes from four populations was nil. We propose that pathogenic variant filtering should be incorporated into variant calling algorithms for mitogenome haplotype reporting to maximize the discriminatory power of the locus while minimizing the reveal of sensitive genetic information.


Assuntos
Algoritmos , DNA Mitocondrial/genética , Variação Genética , Genética Populacional , Genoma Mitocondrial , Haplótipos , Mitocôndrias/genética , DNA Mitocondrial/análise , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Filogenia , Análise de Sequência de DNA
12.
Genes (Basel) ; 11(11)2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-33138247

RESUMO

A total of 1327 platinum-quality mitochondrial DNA haplotypes from United States (U.S.) populations were generated using a robust, semi-automated next-generation sequencing (NGS) workflow with rigorous quality control (QC). The laboratory workflow involved long-range PCR to minimize the co-amplification of nuclear mitochondrial DNA segments (NUMTs), PCR-free library preparation to reduce amplification bias, and high-coverage Illumina MiSeq sequencing to produce an average per-sample read depth of 1000 × for low-frequency (5%) variant detection. Point heteroplasmies below 10% frequency were confirmed through replicate amplification, and length heteroplasmy was quantitatively assessed using a custom read count analysis tool. Data analysis involved a redundant, dual-analyst review to minimize errors in haplotype reporting with additional QC checks performed by EMPOP. Applying these methods, eight sample sets were processed from five U.S. metapopulations (African American, Caucasian, Hispanic, Asian American, and Native American) corresponding to self-reported identity at the time of sample collection. Population analyses (e.g., haplotype frequencies, random match probabilities, and genetic distance estimates) were performed to evaluate the eight datasets, with over 95% of haplotypes unique per dataset. The platinum-quality mitogenome haplotypes presented in this study will enable forensic statistical calculations and thereby support the usage of mitogenome sequencing in forensic laboratories.


Assuntos
DNA Mitocondrial/genética , Genoma Mitocondrial/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Impressões Digitais de DNA/métodos , Feminino , Haplótipos/genética , Humanos , Masculino , Mitocôndrias/genética , Platina/química , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNA/métodos , Estados Unidos/epidemiologia
13.
Forensic Sci Int Genet ; 43: 102143, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31473588

RESUMO

Mitochondrial haplogroup information can be useful in forensic contexts that rely primarily on mitochondrial DNA (mtDNA) testing, which often involve limited or degraded DNA. Due to the phylogeographic patterning of mtDNA in human populations, mitochondrial haplogroups are indicative of maternal ancestry (as mtDNA is a maternally inherited marker). In certain circumstances, maternal ancestry inferred from mitochondrial haplogrouping could be beneficial to forensic investigations. For example, ancestry information could assist in the identification of unknown service members from past conflicts, such as the World War II Battle of Tarawa involving American and Japanese forces. In this context, it could be useful to distinguish Native American mtDNA from Asian mtDNA to bolster the anthropological and circumstantial evidence leading to an identification or foreign national determination. Although most of the founding Native American haplogroups contain diagnostic variants in the mitochondrial control region (CR), haplogroup B2 does not, and this makes it more difficult to distinguish B2 from the parental B4 and closely related B4b haplogroups found in Asia. In this paper, the amount of mtDNA information required to distinguish Native American haplotypes from Asian haplotypes within haplogroup B was examined. Fifty-six samples belonging to subtypes of B2 and B4 were sequenced for the entire mitogenome. Haplogroups were estimated from three ranges of mitochondrial DNA (HV1 and 2, CR, and full mitogenome). Half of the samples could not be precisely haplogrouped without full mitogenome data, although enough variants were often provided to make an accurate B2 versus B4 distinction. Native American B2 haplotypes were distinguishable using CR data alone in 82% of samples, though the remaining samples required full mitogenome data for haplogroup B2 designation. The use of full mitogenome data consistently enables accurate haplogroup determination, and opens the possibility for gaining information on maternal ancestry.


Assuntos
Povo Asiático/genética , DNA Mitocondrial/genética , Genoma Mitocondrial , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Indígenas Norte-Americanos/genética , Humanos , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
14.
Health Phys ; 114(5): 507-510, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29505431

RESUMO

The Health Physics Society (HPS) provided comment to the U.S. Environmental Protection Agency (EPA) on options to consider when developing an action plan for President Trump's Executive Order to evaluate regulations for repeal, replacement, or modification. The HPS recommended that the EPA reconsider their adherence to the linear no-threshold (LNT) model for radiation risk calculations and improve several documents by better addressing uncertainties in low-dose, low dose-rate (LDDR) radiation exposure environments. The authors point out that use of the LNT model near background levels cannot provide reliable risk projections, use of the LNT model and collective-dose calculations in some EPA documents is inconsistent with the recommendations of international organizations, and some EPA documents have not been exposed to the public comment rule-making process. To assist in establishing a better scientific basis for the risks of low dose rate and low dose radiation exposure, the EPA should continue to support the "Million Worker Study," led by the National Council on Radiation Protection and Measurement.


Assuntos
Comitês Consultivos , Física Médica , Proteção Radiológica/legislação & jurisprudência , Proteção Radiológica/normas , Sociedades Médicas , United States Environmental Protection Agency , Humanos , Doses de Radiação , Medição de Risco , Estados Unidos
15.
Acta Crystallogr E Crystallogr Commun ; 73(Pt 10): 1520-1522, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29250371

RESUMO

Single crystals of the title compound, Na(H2AsO4), were obtained by partial neutralization of arsenic acid with sodium hydroxide in aqueous solution. The crystal structure of Na(H2AsO4) is isotypic with the phosphate analogue and the asymmetric unit consists of two sodium cations and two tetra-hedral H2AsO4- anions. Each of the sodium cations is surrounded by six O atoms of five H2AsO4- groups, defining distorted octa-hedral coordination spheres. In the extended structure, the sodium cations and di-hydrogen arsenate anions are arranged in the form of layers lying parallel to (010). Strong hydrogen bonds [range of O⋯O distances 2.500 (3)-2.643 (3) Å] between adjacent H2AsO4- anions are observed within and perpendicular to the layers. The isotypic structure of Na(H2PO4) is comparatively discussed.

16.
Injury ; 48(8): 1853-1857, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28648408

RESUMO

Hip fractures are a major cause of trauma related death, usually occurring in vulnerable elderly patients. There are an estimated 70,000 hip fractures in the UK per year with numbers set to rise. The estimated annual cost to the healthcare economy is in the region of £2 billion. A 17-year review examining litigation related to hip fractures was undertaken. Under a freedom of information request, data was obtained relating to all orthopaedic claims made to the NHS Litigation Authority (NHSLA) between 1995 and 2012. Data was filtered to identify cases involving hip fractures examining litigation trends related to this specific area. 10263 NHSLA orthopaedic cases were identified, of which 13.3% (n=1364) cases related to the hip and femur. Hip fractures made up 16.7% (n=229). The total cost of hip fracture litigation was over £7 million with an average cost per case of £32,700. The commonest reasons for litigation were diagnostic errors (30.6%), issues with care (24.9%) alleged incompetent surgery (15.7%) and development of pressure sores (5.7%). This study highlights the main causes of litigation in patients sustaining hip fractures, with diagnosis in the emergency department and ward presenting a significant problem. In addition, the data identifies a range of care related issues, as well as several surgical factors and highlights the importance of pressure area care. We discuss these and make suggestions on how to improve practice in this area with the aim of improving patient care and reducing litigation.


Assuntos
Compensação e Reparação/legislação & jurisprudência , Erros de Diagnóstico/legislação & jurisprudência , Fixação de Fratura/efeitos adversos , Fraturas do Quadril , Revisão da Utilização de Seguros/estatística & dados numéricos , Ortopedia , Medicina Estatal/legislação & jurisprudência , Bases de Dados Factuais , Erros de Diagnóstico/economia , Fixação de Fratura/economia , Fixação de Fratura/legislação & jurisprudência , Fidelidade a Diretrizes/legislação & jurisprudência , Humanos , Revisão da Utilização de Seguros/legislação & jurisprudência , Imperícia/legislação & jurisprudência , Imperícia/estatística & dados numéricos , Ortopedia/legislação & jurisprudência , Ortopedia/normas , Úlcera por Pressão , Reino Unido
17.
Forensic Sci Int Genet ; 29: 174-180, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28448897

RESUMO

Next-generation sequencing (NGS) facilitates the rapid and high-throughput generation of human mitochondrial genome (mitogenome) data to build population and reference databases for forensic comparisons. To this end, long-range amplification provides an effective method of target enrichment that is amenable to library preparation assays employing DNA fragmentation. This study compared the Nextera XT DNA Library Preparation Kit (Illumina, San Diego, CA) and the KAPA HyperPlus Library Preparation Kit (Kapa Biosystems, Wilmington, MA) for enzymatic fragmentation and indexing of ∼8500bp mitogenome amplicons for Illumina sequencing. The Nextera XT libraries produced low-coverage regions that were consistent across all samples, while the HyperPlus libraries resulted in uniformly high coverage across the mitogenome, even with reduced-volume reaction conditions. The balanced coverage observed from KAPA HyperPlus libraries enables not only low-level variant calling across the mitogenome but also increased sample multiplexing for greater processing efficiency.


Assuntos
Biblioteca Gênica , Genoma Mitocondrial , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Análise de Sequência de DNA
18.
Health Phys ; 88(2 Suppl): S14-6, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15654238

RESUMO

An effective radiation safety program for biomedical research minimizes both external and internal exposures. Limited time and resources can make it difficult to find the right balance between the external dosimetry and internal bioassay components: research typically involves chronic use of small activities rather than acute use of large quantities; concern for external exposures, especially extremities, distracts from the potential for intake; regulatory guidance for only tritium and iodine leave the impression there is little need to monitor for other radionuclides; conversely some licensees over rely on frequent bioassays. Too often researchers discount the potential for intake, especially those who repeatedly use small quantities. This program emphasizes minimizing external and internal exposures while providing the radiation protection staff with criteria for determining the need to assay for any radionuclide under a wide variety of working conditions.


Assuntos
Bioensaio/normas , Radioisótopos/normas , Radiometria/normas , Bioensaio/métodos , Humanos , Doses de Radiação , Radiometria/métodos
19.
Forensic Sci Int Genet ; 14: 141-55, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25450785

RESUMO

Though investigations into the use of massively parallel sequencing technologies for the generation of complete mitochondrial genome (mtGenome) profiles from difficult forensic specimens are well underway in multiple laboratories, the high quality population reference data necessary to support full mtGenome typing in the forensic context are lacking. To address this deficiency, we have developed 588 complete mtGenome haplotypes, spanning three U.S. population groups (African American, Caucasian and Hispanic) from anonymized, randomly-sampled specimens. Data production utilized an 8-amplicon, 135 sequencing reaction Sanger-based protocol, performed in semi-automated fashion on robotic instrumentation. Data review followed an intensive multi-step strategy that included a minimum of three independent reviews of the raw data at two laboratories; repeat screenings of all insertions, deletions, heteroplasmies, transversions and any additional private mutations; and a check for phylogenetic feasibility. For all three populations, nearly complete resolution of the haplotypes was achieved with full mtGenome sequences: 90.3-98.8% of haplotypes were unique per population, an improvement of 7.7-29.2% over control region sequencing alone, and zero haplotypes overlapped between populations. Inferred maternal biogeographic ancestry frequencies for each population and heteroplasmy rates in the control region were generally consistent with published datasets. In the coding region, nearly 90% of individuals exhibited length heteroplasmy in the 12418-12425 adenine homopolymer; and despite a relatively high rate of point heteroplasmy (23.8% of individuals across the entire molecule), coding region point heteroplasmies shared by more than one individual were notably absent, and transversion-type heteroplasmies were extremely rare. The ratio of nonsynonymous to synonymous changes among point heteroplasmies in the protein-coding genes (1:1.3) and average pathogenicity scores in comparison to data reported for complete substitutions in previous studies seem to provide some additional support for the role of purifying selection in the evolution of the human mtGenome. Overall, these thoroughly vetted full mtGenome population reference data can serve as a standard against which the quality and features of future mtGenome datasets (especially those developed via massively parallel sequencing) may be evaluated, and will provide a solid foundation for the generation of complete mtGenome haplotype frequency estimates for forensic applications.


Assuntos
Genética Forense , Genoma Mitocondrial , Haplótipos , Humanos , Estados Unidos
20.
Health Phys ; 86(2 Suppl): S42-7, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14744070

RESUMO

For many, the thought of terrorists detonating a dirty bomb--a radiological dispersal device--is frightening. However, the radiation health risks from such an occurrence are small. For most people directly involved, the exposure would have an estimated lifetime health risk that is comparable to the health risk from smoking five packages of cigarettes or the accident risk from taking a hike. The actual impact of a dirty bomb would be economic and social (NCRP 2001). There would be an economic cost for clean-up as well as a decrease in economic activity in the affected area due to radiation fear. If such a bomb were detonated, those exposed as well as those not exposed would have great concern about potential health effects while seeking medical attention and avoiding the impacted area. This paper discusses the health risks from radiation exposure and compares them to risks from various activities of daily life and to exposure to hazardous chemicals.


Assuntos
Guerra Nuclear , Doses de Radiação , Lesões por Radiação/mortalidade , Cinza Radioativa/análise , Radiometria/métodos , Medição de Risco/métodos , Terrorismo , Humanos , Expectativa de Vida , Fatores de Risco
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