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1.
Proc Natl Acad Sci U S A ; 117(45): 28496-28505, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33097671

RESUMO

Taxonomic resolution is a major challenge in palynology, largely limiting the ecological and evolutionary interpretations possible with deep-time fossil pollen data. We present an approach for fossil pollen analysis that uses optical superresolution microscopy and machine learning to create a quantitative and higher throughput workflow for producing palynological identifications and hypotheses of biological affinity. We developed three convolutional neural network (CNN) classification models: maximum projection (MPM), multislice (MSM), and fused (FM). We trained the models on the pollen of 16 genera of the legume tribe Amherstieae, and then used these models to constrain the biological classifications of 48 fossil Striatopollis specimens from the Paleocene, Eocene, and Miocene of western Africa and northern South America. All models achieved average accuracies of 83 to 90% in the classification of the extant genera, and the majority of fossil identifications (86%) showed consensus among at least two of the three models. Our fossil identifications support the paleobiogeographic hypothesis that Amherstieae originated in Paleocene Africa and dispersed to South America during the Paleocene-Eocene Thermal Maximum (56 Ma). They also raise the possibility that at least three Amherstieae genera (Crudia, Berlinia, and Anthonotha) may have diverged earlier in the Cenozoic than predicted by molecular phylogenies.


Assuntos
Fósseis , Microscopia/métodos , Redes Neurais de Computação , Filogenia , Pólen/classificação , África , África Ocidental , Aprendizado de Máquina , Filogeografia , América do Sul
2.
Dev World Bioeth ; 23(2): 109-121, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36791233

RESUMO

South Africa has an abortion law which codifies the broad themes of reproductive rights set out in the Constitution of South Africa, other laws and national guidelines. Certain wording of the conditions in the Choice Act for abortion after 20 weeks' gestation, are open to interpretation, being 'severe malformation of the fetus' and 'risk of injury to the fetus'. From 24 weeks onwards, abortion is carried out by feticide/induced fetal cardiac asystole ('IFCA') and subsequent induction of labour in South Africa. Some maternal-fetal units have developed guidelines to assist clinicians and patients in decision-making around eligibility for abortion after 20 weeks' gestation, given the broad terms in the law. We consider the guideline used by an institution in the Western Cape for abortion after 23 weeks and 6 days gestation, in terms of its alignment with the law on reproductive rights and its compliance with fair and transparent procedures. We also note its effect on respect for patients and on staff professionalism.


Assuntos
Aborto Induzido , Gestantes , Gravidez , Feminino , Humanos , África do Sul , Idade Gestacional , Feto
3.
Trans Inst Br Geogr ; 47(2): 514-528, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35910281

RESUMO

Using a unique database on investment funds and the conceptual framework of global financial networks, this paper examines the spatial structure of the European investment fund industry, with particular focus on Luxembourg and Ireland. Grounded in financial and economic geography, the paper shows how these countries became the leading investment fund domiciles through a mixture of structural factors and agency enabling a fast and flexible implementation of the European Directive on the Undertakings for the Collective Investment in Transferable Securities (UCITS) of 1985, and the cultivation of the investment fund industry ever since. In the process, Luxembourg and Ireland have built on and developed their functions as offshore jurisdictions and international financial centres, both sustained by their governments and regulatory agencies. The analysis of the functional structure of investment funds and their networked geography reveals the increasingly dominant position of London as the investment management centre for the industry, and the increasing concentration of control by large asset management firms. Stripped to its basics, the geography of European investment fund networks is about large, mainly US, asset management firms, creating and managing funds in Luxembourg and Ireland, and investing money through London. As such, the rise of European investment funds can be seen as an example of European financial integration through Americanisation. The Luxembourg and Irish investment fund industry are connected mainly through London and New York, and thus function as satellites of the NY-LON axis, rather than a Luxembourg-Dublin axis in international finance. Overall, the paper demonstrates that studying this seemingly arcane industry, and the role of two small countries in it, reveals much about the nature of financial globalisation.

4.
Afr J Reprod Health ; 26(8): 53-65, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37585032

RESUMO

Fetal Alcohol Spectrum Disorders (FASD) is a common and under-recognised health burden in South Africa. There is a limited understanding of why pregnant women drink in the South African context, particularly in rural settings, where the prevalence of FASD is highest. A purposive sample included eight women from a rural ante-natal clinic in the Northern Cape province of South Africa. Participants participated in a semi-structured interview. A process of thematic analysis was used to generate themes from the interviews. All participants were aware of the link between alcohol use during pregnancy and adverse fetal outcomes. Furthermore, most participants reduced drinking after pregnancy recognition. Participants described barriers and facilitators of alcohol abstinence. Barriers included social pressure, life stressors, and cravings and habits. Facilitators included the desire to avoid FASD, supportive relationships, availability of alternative activities. Addressing barriers at community and individual levels may aid women in reducing harmful drinking during pregnancy.


Assuntos
Alcoolismo , Transtornos do Espectro Alcoólico Fetal , Feminino , Gravidez , Humanos , Transtornos do Espectro Alcoólico Fetal/epidemiologia , Transtornos do Espectro Alcoólico Fetal/prevenção & controle , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Abstinência de Álcool , Alcoolismo/complicações , Alcoolismo/epidemiologia , Gestantes , África do Sul/epidemiologia
5.
BMC Med Genet ; 21(1): 124, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503528

RESUMO

BACKGROUND: The X-linked recessive primary immunodeficiency disease (PIDD) Wiskott-Aldrich syndrome (WAS) is identified by an extreme susceptibility to infections, eczema and thrombocytopenia with microplatelets. The syndrome, the result of mutations in the WAS gene which encodes the Wiskott-Aldrich protein (WASp), has wide clinical phenotype variation, ranging from classical WAS to X-linked thrombocytopaenia and X-linked neutropaenia. In many cases, the diagnosis of WAS in first affected males is delayed, because patients may not present with the classic signs and symptoms, which may intersect with other thrombocytopenia causes. CASE PRESENTATION: Here, we describe a three-year-old HIV negative boy presenting with recurrent infections, skin rashes, features of autoimmunity and atopy. However, platelets were initially reported as normal in numbers and morphology as were baseline immune investigations. An older male sibling had died in infancy from suspected immunodeficiency. Uncertainty of diagnosis and suspected severe PIDD prompted urgent further molecular investigation. Whole exome sequencing identified c. 397 G > A as a novel hemizygous missense mutation located in exon 4 of WAS. CONCLUSION: With definitive molecular diagnosis, we could target treatment and offer genetic counselling and prenatal diagnostic testing to the family. The identification of novel variants is important to confirm phenotype variations of a syndrome.


Assuntos
Mutação/genética , Proteína da Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/genética , Sequência de Aminoácidos , Sequência de Bases , Feminino , Humanos , Lactente , Masculino , Volume Plaquetário Médio , Linhagem , África do Sul , Síndrome de Wiskott-Aldrich/sangue , Proteína da Síndrome de Wiskott-Aldrich/química
6.
Am J Med Genet A ; 182(10): 2230-2235, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32845056

RESUMO

Hyperphosphatasia with mental retardation syndrome (HPMRS) is a rare autosomal recessive disorder caused by pathogenic variants in genes involved in glycosylphosphatidylinositol metabolism that result in a similar phenotype. We describe the first three patients with HPMRS from sub-Saharan Africa. Detection was assisted by Face2Gene phenotype matching and confirmed by the presence of elevated serum alkaline phosphatase. All three patients had severe intellectual disability, absent speech, hypotonia and palatal abnormality (cleft palate in two, very high-arched palate in one), no or minimal brachytelephalangy, and high serum alkaline phosphatase levels. Additional findings included seizures in two, and brain imaging abnormalities in two. In all three patients HPMRS was a top-20 gestalt match using Face2Gene. The overall phenotype is consistent with descriptions in the literature of HPMRS type 4, although not specific to it. Whole exome sequencing in the index patient and his mother detected a candidate variant in a homozygous state in the index patient (PGAP3:c.557G>C, p.Arg186Thr) and heterozygous in the mother. Further variant interpretation indicated pathogenicity. Sanger sequencing of another two patients identified the same homozygous, pathogenic variant, confirming a diagnosis of HPMRS type 4. The shared homozygous variant in apparently unrelated families, and in the absence of consanguinity, suggests the possibility of genetic drift due to a population bottleneck effect, and further research is recommended.


Assuntos
Anormalidades Múltiplas/genética , Encéfalo/diagnóstico por imagem , Hidrolases de Éster Carboxílico/genética , Predisposição Genética para Doença , Deficiência Intelectual/genética , Distúrbios do Metabolismo do Fósforo/genética , Receptores de Superfície Celular/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/patologia , África Subsaariana , Encéfalo/patologia , Pré-Escolar , Consanguinidade , Feminino , Homozigoto , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/patologia , Masculino , Mutação/genética , Linhagem , Distúrbios do Metabolismo do Fósforo/diagnóstico , Distúrbios do Metabolismo do Fósforo/diagnóstico por imagem , Distúrbios do Metabolismo do Fósforo/patologia , Sequenciamento do Exoma
7.
Anesthesiology ; 133(2): 350-363, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32433277

RESUMO

BACKGROUND: Prospective trials of enhanced recovery after spine surgery are lacking. We tested the hypothesis that an enhanced recovery pathway improves quality of recovery after one- to two-level lumbar fusion. METHODS: A patient- and assessor-blinded trial of 56 patients randomized to enhanced recovery (17 evidence-based pre-, intra-, and postoperative care elements) or usual care was performed. The primary outcome was Quality of Recovery-40 score (40 to 200 points) at postoperative day 3. Twelve points defined the clinically important difference. Secondary outcomes included Quality of Recovery-40 at days 0 to 2, 14, and 56; time to oral intake and discharge from physical therapy; length of stay; numeric pain scores (0 to 10); opioid consumption (morphine equivalents); duration of intravenous patient-controlled analgesia use; complications; and markers of surgical stress (interleukin 6, cortisol, and C-reactive protein). RESULTS: The analysis included 25 enhanced recovery patients and 26 usual care patients. Significantly higher Quality of Recovery-40 scores were found in the enhanced recovery group at postoperative day 3 (179 ± 14 vs. 170 ± 16; P = 0.041) without reaching the clinically important difference. There were no significant differences in recovery scores at days 0 (175 ± 16 vs. 162 ± 22; P = 0.059), 1 (174 ± 18 vs. 164 ± 15; P = 0.050), 2 (174 ± 18 vs. 167 ± 17; P = 0.289), 14 (184 ± 13 vs. 180 ± 12; P = 0.500), and 56 (187 ± 14 vs. 190 ± 8; P = 0.801). In the enhanced recovery group, subscores on the Quality of Recovery-40 comfort dimension were higher (longitudinal mean score difference, 4; 95% CI, 1, 7; P = 0.008); time to oral intake (-3 h; 95% CI, -6, -0.5; P = 0.010); and duration of intravenous patient-controlled analgesia (-11 h; 95% CI, -19, -6; P < 0.001) were shorter; opioid consumption was lower at day 1 (-57 mg; 95% CI, -130, -5; P = 0.030) without adversely affecting pain scores (-2; 95% CI, -3, 0; P = 0.005); and C-reactive protein was lower at day 3 (6.1; 95% CI, 3.8, 15.7 vs. 15.9; 95% CI, 6.6, 19.7; P = 0.037). CONCLUSIONS: Statistically significant gains in early recovery were achieved by an enhanced recovery pathway. However, significant clinical impact was not demonstrated.


Assuntos
Vértebras Lombares/cirurgia , Cuidados Pós-Operatórios/normas , Cuidados Pré-Operatórios/normas , Qualidade da Assistência à Saúde/normas , Recuperação de Função Fisiológica/fisiologia , Fusão Vertebral/normas , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/prevenção & controle , Cuidados Pós-Operatórios/tendências , Cuidados Pré-Operatórios/tendências , Estudos Prospectivos , Qualidade da Assistência à Saúde/tendências , Fusão Vertebral/tendências
8.
J Trop Pediatr ; 66(4): 441-447, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31943102

RESUMO

INTRODUCTION: In 2011, the American Academy of Paediatrics (AAP) published revised health supervision guidelines for children with Down syndrome (DS). In the absence of South African guidelines, we described the health supervision received by children with DS at a rural regional hospital in the Western Cape, South Africa compared with the AAP guidelines. METHODS: This was a 5-year retrospective description of the implementation of the 2011 AAP guidelines at the DS clinic at Worcester Provincial Hospital (WPH), specifically related to screening for and management of cardiac, thyroid, hearing and haematological disorders. RESULTS: Sixty-two children received care at WPH DS clinic during the study period. Thirty-six (58%) children lived in Worcester while 26 (42%) children were referred from peripheral hospitals. The median age at first clinic visit was 0.5 years [inter-quartile range (IQR) 0.2-1.2], a total of 177 person-years of follow-up with a median duration of 1.8 years (IQR 0.3-4.8). Two deaths occurred during the study period. Forty-nine (79%) children had a screening echocardiogram performed, the median age at first echocardiogram was 0.8 years (IQR 0.2-1.4). Five (14%) children from WPH compared with no children from the peripheral hospitals received the echocardiogram within the first month of life in keeping with AAP guidance (p = 0.06). Those requiring cardiac surgery were operated on at a median age of 2 years (IQR 0.9-2.3). Compared with the AAP guidelines, within the first month of life 17 (27%) children had a thyroid screen, 20 (32%) children had a full blood count and 7 (11%) children had a hearing assessment. CONCLUSION: AAP guidelines for health supervision in DS are challenging to achieve within our local health system. The development and advocacy for a South African DS health supervision guideline that can be applied not only in specialist clinics might improve the care of children with DS.


Assuntos
Síndrome de Down/terapia , Fidelidade a Diretrizes , Pediatria/normas , Criança , Pré-Escolar , Síndrome de Down/diagnóstico , Síndrome de Down/etnologia , Feminino , Seguimentos , Aconselhamento Genético , Conhecimentos, Atitudes e Prática em Saúde , Hospitais , Humanos , Perda de Seguimento , Masculino , Educação de Pacientes como Assunto , Pediatria/métodos , População Rural , África do Sul
9.
Genes Immun ; 20(6): 447-454, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30185814

RESUMO

While individual primary immunodeficiency diseases (PIDs) are rare, collectively they represent a significant burden of disease. Recent estimates show that about one million people in Africa suffer from a PID. However, data from African PID registries reflect only a small percentage of the estimated prevalence. This disparity is partly due to the lack of PID awareness and the masking of PIDs by the endemic pathogens. Over three million tuberculosis (TB) cases were reported in Africa in 2016, with many of these from southern Africa. Despite concerted efforts to address this high burden of disease, the underlying genetic correlates of susceptibility to TB remain poorly understood. High penetrance mutations in immune system genes can cause PIDs that selectively predispose individuals to TB and other mycobacterial diseases. Additionally, the identification of individuals at a heightened risk of developing TB or of presenting with severe or disseminated TB due to their genetic ancestry is crucial to promote a positive treatment outcome. The screening for and identification of PID mutations in TB-endemic regions by next-generation sequencing (NGS) represents a promising approach to improve the understanding of what constitutes an effective immune response to TB, as well as the range of associated PIDs and phenotypes.


Assuntos
Doenças da Imunodeficiência Primária/genética , Tuberculose/epidemiologia , África Austral/epidemiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/epidemiologia , Doenças da Imunodeficiência Primária/imunologia
10.
Anesth Analg ; 129(2): 487-492, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30418236

RESUMO

BACKGROUND: Prone positioning (PP) is necessary for surgical access during posterior spine procedure. However, physiological changes occur in the PP. Typical findings are a decrease in arterial blood pressure and in cardiac output that could potentially lead to an alteration in cerebral perfusion. Therefore, we decided to study cerebral blood flow velocity (CBFV) with transcranial Doppler ultrasonography to evaluate the effect of the PP on cerebral hemodynamics. METHODS: Twenty-two patients undergoing spine surgery in the PP were studied. General anesthesia was induced using 250 µg of fentanyl, 2 mg/kg of propofol, and 0.1 mg/kg of vecuronium, and was maintained with 0.25%-0.5% isoflurane, 50% nitrous oxide in oxygen, continuous infusion of 100 µg/kg/min of propofol, 1.5 µg/kg/h of fentanyl, and 0.15 mg/kg/h of ketamine. Continuous invasive arterial blood pressure, heart rate, electrocardiogram, and end-tidal carbon dioxide were monitored. CBFV with transcranial Doppler in the middle cerebral artery was first measured with the patients under general anesthesia in the supine position. Patients were then placed in the PP and remained in this position throughout surgery. CBFV, end-tidal carbon dioxide, heart rate, and blood pressure were measured continuously for 75 minutes after initiation of PP. This coincided with surgical exposure and minimal blood loss. Data were analyzed every 15 minutes for statistical significant change over time. RESULTS: Mean arterial blood pressure decreased 15 minutes after the installation of the PP and onward, but this decrease was not statistically significant. CBFVsyst (the maximal CBFV during the systolic phase of a cardiac cycle) and CBFVmean (the time averaged value of the maximal velocity envelope over 1 cardiac cycle) did not vary at any time points. CBFVdiast (the CBFV just before the acceleration phase [systole] of the next waveform) was lower at T3 (30 minutes after PP) compared to T1 (value derived averaging the first measure in the PP with the ones at 5 and 10 minutes) (P = .01), and the pulsatility index was higher at T5 (60 minutes after PP) compared to T0 (baseline, patient supine under general anesthesia) (P = .04). Data were analyzed at specific time points (T0 and T1). This value was derived by computing an average of the CBFV values collected at the first measure in the PP and at 5 and 10 minutes thereafter: T2, 15 minutes after PP; T3, 30 minutes after PP; T4, 45 minutes after PP; T5, 60 minutes after PP; and T6, 75 minutes after PP. CONCLUSIONS: Our data on CBFV during PP for spine surgery demonstrate preservation of cerebral perfusion during stable systemic hemodynamic conditions. The present results do not allow us to determine whether the PP would be similarly tolerated with increasing length of surgery, variations in systemic hemodynamics, and in different patient populations.


Assuntos
Circulação Cerebrovascular , Vértebras Lombares/cirurgia , Artéria Cerebral Média/fisiologia , Procedimentos Ortopédicos , Posicionamento do Paciente , Decúbito Ventral , Adolescente , Adulto , Idoso , Pressão Arterial , Velocidade do Fluxo Sanguíneo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Estudos Prospectivos , Fatores de Tempo , Ultrassonografia Doppler Transcraniana , Adulto Jovem
11.
Nano Lett ; 18(6): 3901-3910, 2018 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-29741381

RESUMO

Membrane proteins involved in transport processes are key targets for pharmaceutical research and industry. Despite continuous improvements and new developments in the field of electrical readouts for the analysis of transport kinetics, a well-suited methodology for high-throughput characterization of single transporters with nonionic substrates and slow turnover rates is still lacking. Here, we report on a novel architecture of silicon chips with embedded nanopore microcavities, based on a silicon-on-insulator technology for high-throughput optical readouts. Arrays containing more than 14 000 inverted-pyramidal cavities of 50 femtoliter volumes and 80 nm circular pore openings were constructed via high-resolution electron-beam lithography in combination with reactive ion etching and anisotropic wet etching. These cavities feature both, an optically transparent bottom and top cap. Atomic force microscopy analysis reveals an overall extremely smooth chip surface, particularly in the vicinity of the nanopores, which exhibits well-defined edges. Our unprecedented transparent chip design provides parallel and independent fluorescent readout of both cavities and buffer reservoir for unbiased single-transporter recordings. Spreading of large unilamellar vesicles with efficiencies up to 96% created nanopore-supported lipid bilayers, which are stable for more than 1 day. A high lipid mobility in the supported membrane was determined by fluorescent recovery after photobleaching. Flux kinetics of α-hemolysin were characterized at single-pore resolution with a rate constant of 0.96 ± 0.06 × 10-3 s-1. Here, we deliver an ideal chip platform for pharmaceutical research, which features high parallelism and throughput, synergistically combined with single-transporter resolution.


Assuntos
Proteínas de Membrana/análise , Nanoporos/ultraestrutura , Análise Serial de Proteínas/instrumentação , Desenho de Equipamento , Proteínas Hemolisinas/análise , Cinética , Bicamadas Lipídicas/química , Modelos Moleculares , Imagem Óptica/instrumentação , Silício/química
12.
J Environ Sci Health B ; 54(2): 98-111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30600768

RESUMO

In this study, a two-dimensional liquid chromatography tandem mass spectrometry method was developed and validated for the determination of pesticide residues and contaminants in whole wheat grains and oats. The samples were extracted with a mixture of acetonitrile and water and were injected into the two-dimensional LC-MS/MS system without any further clean-up or sample preparation. Samples were analyzed with four different matrix matched calibrations. Matrix effects were evaluated by comparing analyte signals in the respective matrix matched standard with the neat solvent standards. The final method was validated according to the current Eurachem validation guide and SANTE document. The number of successfully validated analytes throughout all three validation levels in oats and wheat, respectively, were as follows: 330 and 316 out of 370 pesticides, 6 and 13 out of 18 pyrrolizidine alkaloids and 7 out of 9 regulated mycotoxins. Moreover, both plant growth regulators mepiquat and chlormequat as well as the tropane alkaloids atropine and scopolamine met the validation criteria. The majority of pesticides showed limits of detection below 1 µg kg-1, pyrrolizidine alkaloids below 0.7 µg kg-1, tropane alkaloids below 0.2 µg kg-1, growth regulators below 0.7 µg kg-1 and mycotoxins below 8 µg kg-1 in both matrices.


Assuntos
Avena/química , Cromatografia Líquida/métodos , Contaminação de Alimentos/análise , Espectrometria de Massas em Tandem/métodos , Triticum/química , Clormequat/análise , Análise de Alimentos/métodos , Limite de Detecção , Micotoxinas/análise , Sistemas On-Line , Resíduos de Praguicidas/análise , Piperidinas/análise , Reguladores de Crescimento de Plantas/análise , Alcaloides de Pirrolizidina/análise , Reprodutibilidade dos Testes , Tropanos/análise
13.
Wien Med Wochenschr ; 169(9-10): 222-225, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29147868

RESUMO

Hydrogen peroxide has been used in medicine for more than 100 years. It is known in surgery as a highly useful irrigation solution by virtue of both its hemostatic and its antimicrobial effects. Due to its possible negative effect on wound healing and its cytotoxic effect in higher concentrations, there are concerns about the safety of its use. The objective of this paper is to review the safety and beneficial effects of hydrogen peroxide.


Assuntos
Peróxido de Hidrogênio/efeitos adversos , Peróxido de Hidrogênio/farmacologia , Cicatrização , Humanos , Procedimentos Cirúrgicos Operatórios , Cicatrização/efeitos dos fármacos
14.
J Environ Manage ; 220: 149-162, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29777998

RESUMO

Future urban development and climatic changes are likely to affect hydrologic regimes in many watersheds. Quantifying potential water regime changes caused by these stressors is therefore crucial for enabling decision makers to develop viable environmental management strategies. This study presents an approach that integrates mid-21st century impervious surface growth estimates derived from the Imperviousness Change Analysis Tool with downscaled climate model projections and a hydrologic model Soil and Water Assessment Tool to characterize potential water regime changes in a mixed-use watershed in central Missouri, USA. Results for the climate change only scenario showed annual streamflow and runoff decreases (-10.7% and -9.2%) and evapotranspiration increases (+6.8%), while results from the urbanization only scenario showed streamflow and runoff increases (+3.8% and +9.3%) and evapotranspiration decreases (-2.4%). Results for the combined impacts scenario suggested that climatic changes could have a larger impact than urbanization on annual streamflow, (overall decrease of -6.1%), and could largely negate surface runoff increases caused by urbanization. For the same scenario, climatic changes exerted a stronger influence on annual evapotranspiration than urbanization (+3.9%). Seasonal results indicated that the relative influences of urbanization and climatic changes vary seasonally. Climatic changes most greatly influenced streamflow and runoff during winter and summer, and evapotranspiration during summer. During some seasons the directional change for hydrologic processes matched for both stressors. This work presented a practicable approach for investigating the relative influences of mid-21st century urbanization and climatic changes on the hydrology of a representative mixed-use watershed, adding to a limited body of research on this topic. This was done using a transferrable approach that can be adapted for watersheds in other regions.


Assuntos
Mudança Climática , Urbanização , Abastecimento de Água , Hidrologia , Missouri , Modelos Teóricos , Rios , Movimentos da Água
15.
Molecules ; 23(2)2018 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-29401708

RESUMO

Antimicrobial peptides (AMPs) have been an area of great interest, due to the high selectivity of these molecules toward bacterial targets over host cells and the limited development of bacterial resistance to these molecules throughout evolution. The peptide C18G has been shown to be a selective, broad spectrum AMP with a net +8 cationic charge from seven lysine residues in the sequence. In this work, the cationic Lys residues were replaced with other natural or non-proteinogenic cationic amino acids: arginine, histidine, ornithine, or diaminopropionic acid. These changes vary in the structure of the amino acid side chain, the identity of the cationic moiety, and the pKa of the cationic group. Using a combination of spectroscopic and microbiological methods, the influence of these cationic groups on membrane binding, secondary structure, and antibacterial activity was investigated. The replacement of Lys with most other cationic residues had, at most, 2-fold effects on minimal inhibitory concentration against a variety of Gram-positive and Gram-negative bacteria. However, the peptide containing His as the cationic group showed dramatically reduced activity. All peptide variants retained the ability to bind lipid vesicles and showed clear preference for binding vesicles that contained anionic lipids. Similarly, all peptides adopted a helical conformation when bound to lipids or membrane mimetics, although the peptide containing diaminopropionic acid exhibited a decreased helicity. The peptides exhibited a wider variety of activity in the permeabilization of bacterial membranes, with peptides containing Lys, Arg, or Orn being the most broadly active. In all, the antibacterial activity of the C18G peptide is generally tolerant to changes in the structure and identity of the cationic amino acids, yielding new possibilities for design and development of AMPs that may be less susceptible to immune and bacterial recognition or in vivo degradation.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Arginina/química , Histidina/química , Lisina/química , Ornitina/química , Peptídeos/química , Propionatos/química , Sequência de Aminoácidos , Substituição de Aminoácidos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Membranas Artificiais , Testes de Sensibilidade Microbiana , Peptídeos/farmacologia , Fosfatidilcolinas/química , Fosfatidilgliceróis/química , Ligação Proteica , Eletricidade Estática , Relação Estrutura-Atividade
16.
BMC Med Genet ; 18(1): 26, 2017 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-28292286

RESUMO

BACKGROUND: Trichohepatoenteric syndrome (THE-S) or phenotypic diarrhoea of infancy is a rare autosomal recessive disorder characterised by severe infantile diarrhoea, facial dysmorphism, immunodeficiency and woolly hair. It was first described in 1982 in two infants with intractable diarrhoea, liver cirrhosis and abnormal hair structure on microscopy. We report on two siblings from a consanguineous family of Somali descent who, despite extensive clinical investigation, remained undiagnosed until their demise. The index patient died of fulminant cytomegalovirus pneumonitis at 3 months of age. METHODS: Whole exome sequencing (WES) was performed on a premortem DNA sample from the index case. Variants in a homozygous recessive state or compound heterozygous state were prioritized as potential candidate variants using TAPER™. Sanger sequencing was done to genotype the parents, unaffected sibling and a deceased sibling for the variant of interest. RESULTS: Exome sequencing identified a novel homozygous mutation (c.4507C > T, rs200067423) in TTC37 which was confirmed by Sanger sequencing in the index case. The identification of this mutation led to the diagnosis of THE-S in the proband and the same homozygous variant was confirmed in a male sibling who died 4 years earlier with severe chronic diarrhoea of infancy. The unaffected parents and sister were heterozygous for the identified variant. CONCLUSIONS: WES permitted definitive genetic diagnosis despite an atypical presentation in the index case and suggests that severe infection, likely secondary to immunodeficiency, may be a presenting feature. In addition definitive molecular diagnosis allows for genetic counseling and future prenatal diagnosis, and demonstrates the value of WES for post-mortem diagnosis of disorders with a non-specific clinical presentation in which a Mendelian cause is suspected.


Assuntos
Proteínas de Transporte/genética , Diarreia Infantil/diagnóstico , Retardo do Crescimento Fetal/diagnóstico , Doenças do Cabelo/diagnóstico , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , Autopsia , Diarreia Infantil/genética , Exoma , Fácies , Evolução Fatal , Retardo do Crescimento Fetal/genética , Doenças do Cabelo/genética , Humanos , Lactente , Masculino , África do Sul
17.
Value Health ; 20(8): 1092-1099, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28964441

RESUMO

BACKGROUND: Partially implantable active middle ear implants (aMEIs) offer a solution for individuals who have mild to severe sensorineural hearing loss and an outer ear medical condition that precludes the use of hearing aids. When otherwise left untreated, individuals report a lower quality of life, which may further decrease with increasing disability. In the lack of cost-effectiveness studies and long-term data, there is a need for decision modeling. OBJECTIVE: To explore individual-level variance in resource utilization patterns following aMEI implantation. METHODS: A Markov model was developed and analyzed as microsimulation to estimate the incremental cost utility ratio (ICUR) of partially implantable aMEIs compared with no (surgical) intervention in individuals with sensorineural hearing loss and an outer ear medical condition in Australia. Cost data were derived mostly from the Medicare Benefit Schedule and effectiveness data from published literature. A third-party payer perspective was adopted, and a 5% discount rate was applied over a 10-year time horizon. RESULTS: Compared with baseline strategy, aMEIs yielded an incremental cost of Australian dollars (AUD) 13,339.18, incremental quality-adjusted life-year (QALY) of 1.35, and an ICUR of AUD 9,913.72/QALY. Of the respective number of simulated patients who visited each health state, 75.73% never had a minor adverse event, 99.82% did not experience device failure, and 97.75% did not cease to use their aMEIs. Probabilistic sensitivity analyses showed the ICUR to differ by only 0.95%. CONCLUSIONS: In the Australian setting, partially implantable aMEIs offer a safe and cost-effective solution compared with no intervention and are also well accepted by users.


Assuntos
Perda Auditiva Neurossensorial/cirurgia , Prótese Ossicular/economia , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Adolescente , Adulto , Idoso , Austrália , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Feminino , Perda Auditiva Neurossensorial/economia , Humanos , Reembolso de Seguro de Saúde , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
18.
Acta Paediatr ; 106(11): 1802-1810, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28685855

RESUMO

AIM: This study examined the effects of prenatal alcohol exposure on childhood development trajectories in a rural South African community between 2003 and 2008. METHODS: We assessed 121 children at 7-12 months (year one) and 5-6 years (year five) using the Griffiths Mental Developmental Scales - Extended Revised, which measures sensorimotor, cognitive and social development, with lower scores indicating developmental delay. We also interviewed their mothers or caregivers. Three groups were identified: 29 with foetal alcohol syndrome (FAS) or partial FAS (pFAS), 57 more who had been exposed to alcohol and 35 controls who had not. RESULTS: The scale's total score was higher in the controls than in the FAS/pFAS group at year one and year five and in the alcohol-exposed group at year five. Many groups' trajectories declined when compared with global norms, but the trajectories in the FAS/pFAS and the alcohol-exposed groups declined more than the controls for eye-hand and performance and total score. Earlier pregnancy recognition in the FAS/pFAS group correlated strongly (r = -0.77) with higher GQ in year five. CONCLUSION: FAS/pFAS and prenatal alcohol exposure affected the Griffiths scores more than the control group. Efforts are needed to detect pregnancy early and reduce alcohol exposure.


Assuntos
Desenvolvimento Infantil , Transtornos do Espectro Alcoólico Fetal/fisiopatologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Transtornos do Espectro Alcoólico Fetal/epidemiologia , Humanos , Lactente , Masculino , África do Sul/epidemiologia
19.
Ecology ; 96(3): 642-53, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26236861

RESUMO

Various environmental factors, including atmospheric CO2 (pCO2), regional climate, and fire, have been invoked as primary drivers of long-term variation in C4 grass abundance. Evaluating these hypotheses has been difficult because available paleorecords often lack information on past C4 grass abundance or potential environmental drivers. We analyzed carbon isotope ratios (delta13C) of individual grains of grass pollen in the sediments of two East African lakes to infer changes in the relative abundance of C3 vs. C4 grasses during the past 25 000 years. Results were compared with concurrent changes in pCO2, temperature, moisture balance, and fire activity. Our grass-pollen delta13C analysis reveals a dynamic history of grass-dominated vegetation in equatorial East Africa: C4 grasses have not consistently dominated lowland areas, and high-elevation grasses have not always been predominantly C3. On millennial timescales, C4 grass abundance does not correlate with charcoal influx at either site, suggesting that fire was not a major proximate control of the competitive balance between C3 and C4 grasses. Above the present-day treeline on Mt. Kenya, C4 grass abundance declined from an average of approximately 90% during the glacial period to less than approximately 60% throughout the Holocene, coincident with increases in pCO2 and temperature, and shifts in moisture balance. In the lowland savanna southeast of Mt. Kilimanjaro, C4 grass abundance showed no such directional trend, but fluctuated markedly in association with variation in rainfall amount and seasonal-drought severity. These results underscore spatiotemporal variability in the relative influence of pCO2 and climate on the interplay of C3 and C4 grasses and shed light on an emerging conceptual model regarding the expansion of C4-dominated grasslands in Earth's history. They also suggest that future changes in the C3/C4 composition of grass-dominated ecosystems will likely exhibit striking spatiotemporal variability as a result of varying combinations of environmental controls.


Assuntos
Dióxido de Carbono/análise , Clima , Incêndios , Poaceae/fisiologia , Atmosfera , Carbono/química , Ciclo do Carbono , Isótopos de Carbono/metabolismo , Pradaria , Quênia , Paleontologia , Poaceae/química , Densidade Demográfica
20.
Alcohol Clin Exp Res ; 39(6): 1016-26, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25941030

RESUMO

BACKGROUND: Fetal alcohol spectrum disorder (FASD) and fetal alcohol syndrome (FAS) are common in some South African populations, notably those of mixed ancestry descent in rural areas and small towns. Little is known about FAS/FASD prevalence in the majority of South Africans: city dwellers of Black African ethnicity. This study describes the prevalence of FAS in a South African city, comparing 2 suburbs with predominantly mixed ancestry (Roodepan) and Black African (Galeshewe) populations that house over 60% of the city population. METHODS: We conducted a tiered, active case ascertainment study for the prevalence of FAS and also detected some less clinically specific FASD cases. All first-grade learners in the 2 suburbs were eligible for anthropometric screening, and screen-positive learners were assessed for dysmorphic features of FAS. Those with suggestive clinical features received neurocognitive assessment, and maternal or collateral interview. Final diagnosis was made following a case conference. RESULTS: Complete ascertainment of FAS status was made in 1,503 (94.7%) of 1,587 eligible learners (435 in Roodepan and 1,152 in Galeshewe). Overall, FAS was diagnosed in 83 (5.5%, 95% confidence interval [CI] = 4.4 to 6.8) learners and FASD in 96 (6.4%, 95% CI = 5.2 to 7.7). Levels of FAS were high in both areas: 26 (6.3%, 95% CI = 4.2 to 9.2) learners from Roodepan, compared to 57 (5.2%, 95% CI = 4.0 to 6.7) from Galeshewe (p = 0.39). No cases were previously diagnosed. The mortality rate for mothers of FASD children from Galeshewe was 19 of 65 (29%), compared to 3 of 31 (9.7%; p = 0.03) for Roodepan. Interviewed mothers in Galeshewe were older and had higher body mass index. CONCLUSIONS: Prevalence of FAS is high in both Galeshewe and Roodepan, and the lack of prior diagnoses indicates that awareness remains low. The maternal mortality rate was especially high in Galeshewe. The unexpectedly high burden of FAS in an urban area with predominantly Black African population mandates extension of surveillance and intervention measures in southern Africa.


Assuntos
População Negra/estatística & dados numéricos , Transtornos do Espectro Alcoólico Fetal/epidemiologia , População Urbana/estatística & dados numéricos , Adulto , Criança , Feminino , Humanos , Masculino , Mortalidade Materna , Prevalência , Fatores de Risco , África do Sul/epidemiologia
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