Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 163
Filtrar
1.
Sci Adv ; 10(15): eadj0954, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38608027

RESUMO

Occupied between ~10,300 and 9300 years ago, the Pre-Pottery Neolithic site of Asikli Höyük in Central Anatolia went through early phases of sheep domestication. Analysis of 629 mitochondrial genomes from this and numerous sites in Anatolia, southwest Asia, Europe, and Africa produced a phylogenetic tree with excessive coalescences (nodes) around the Neolithic, a potential signature of a domestication bottleneck. This is consistent with archeological evidence of sheep management at Asikli Höyük which transitioned from residential stabling to open pasturing over a millennium of site occupation. However, unexpectedly, we detected high genetic diversity throughout Asikli Höyük's occupation rather than a bottleneck. Instead, we detected a tenfold demographic bottleneck later in the Neolithic, which caused the fixation of mitochondrial haplogroup B in southwestern Anatolia. The mitochondrial genetic makeup that emerged was carried from the core region of early Neolithic sheep management into Europe and dominates the matrilineal diversity of both its ancient and the billion-strong modern sheep populations.


Assuntos
Genoma Mitocondrial , Animais , Ovinos/genética , Filogenia , Carneiro Doméstico/genética , Turquia , África
2.
J Homosex ; 71(5): 1177-1200, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36688863

RESUMO

There are currently debates inside and outside intersex communities about whether to include the I in LGBTQI+. Intersex has historically been critical in arguments about the boundaries between significant ontological and epistemological categories, particularly: female and male; homosexuality and heterosexuality; and sex, gender and sexuality. There is also a long history of conflation and confusion of categories of sex, gender and sexuality. It is clear that intersex is in some way inseparable from LGBT politics. This article will present the historical case study of Georgina Somerset, a British intersex woman, focusing on 1960-1970. Somerset's story illustrates both that intersex is different and separate from issues of gender and sexuality, and that intersex is always intimately connected to LGBT issues, whether historically or in contemporary politics. I identify four contemporary tensions that can be illuminated by this history of the entanglements and tensions of LGBT and I: the difficult boundary work between intersex and trans; the association of both intersex and trans with homosexuality; the issues of distraction and instrumentalization; and the affordances and limitations of identity politics. As the "I" was there all along, the politics of recognition might help us generate different discussions of LGBTQI+ politics and responsibilities.


Assuntos
Transtornos do Desenvolvimento Sexual , Minorias Sexuais e de Gênero , Transexualidade , Humanos , Masculino , Feminino , Homossexualidade , Identidade de Gênero , Heterossexualidade
3.
Curr Biol ; 33(21): 4751-4760.e14, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37935117

RESUMO

Domestic cats were derived from the Near Eastern wildcat (Felis lybica), after which they dispersed with people into Europe. As they did so, it is possible that they interbred with the indigenous population of European wildcats (Felis silvestris). Gene flow between incoming domestic animals and closely related indigenous wild species has been previously demonstrated in other taxa, including pigs, sheep, goats, bees, chickens, and cattle. In the case of cats, a lack of nuclear, genome-wide data, particularly from Near Eastern wildcats, has made it difficult to either detect or quantify this possibility. To address these issues, we generated 75 ancient mitochondrial genomes, 14 ancient nuclear genomes, and 31 modern nuclear genomes from European and Near Eastern wildcats. Our results demonstrate that despite cohabitating for at least 2,000 years on the European mainland and in Britain, most modern domestic cats possessed less than 10% of their ancestry from European wildcats, and ancient European wildcats possessed little to no ancestry from domestic cats. The antiquity and strength of this reproductive isolation between introduced domestic cats and local wildcats was likely the result of behavioral and ecological differences. Intriguingly, this long-lasting reproductive isolation is currently being eroded in parts of the species' distribution as a result of anthropogenic activities.


Assuntos
Felis , Hibridização Genética , Humanos , Gatos/genética , Animais , Bovinos , Abelhas , Ovinos , Suínos , Galinhas , Felis/genética , Europa (Continente) , Fluxo Gênico
4.
Animals (Basel) ; 13(18)2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37760331

RESUMO

Detailed knowledge related to the morphology, anatomy, physiology, and pathology of the canine mammary gland is scarce. Mammary tissue undergoes massive changes instructed by hormones multiple times within the lifespan of every bitch, affecting its appearance. To address the ductal system's appearance and to present how different our findings regarding the canine mammary gland are in comparison with the available literature, we obtained cadaveric specimens after euthanasia and mastectomy. All bitches were euthanised due to poor prognosis for their recovery from maladies unrelated to mammae. Using intraductal cannulation ex vivo, milk- or fluid-yielding ducts were perfused using VasQtec (polyurethane resin), which revealed casts, i.e., imprints of ducts and glandular structures in situ. We observed primary, vertically positioned ducts that ascended throughout the teat and continued branching to secondary, tertiary, etc., horizontally positioned ducts, which drained mammary gland lobes under the skin located close to the abdominal wall. The ascendant teat canal could be split into two and could be connected to gland alveoli or end blind. Alveolar formations were located along ducts and ductules in bigger and/or smaller clusters. This study is the first to generate a 3D image of canine ducts and glandular tissue using an intraductal approach.

5.
Cancer Res Commun ; 3(3): 444-458, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36936664

RESUMO

Metastatic prostate cancer is essentially incurable and is a leading cause of cancer-related morbidity and mortality in men, yet the underlying molecular mechanisms are poorly understood. Plexins are transmembrane receptors for semaphorins with divergent roles in many forms of cancer. We show here that prostate epithelial cell-specific expression of a mutant form of Plexin-B1 (P1597L) which was identified in metastatic deposits in patients with prostate cancer, significantly increases metastasis, in particular metastasis to distant sites, in two transgenic mouse models of prostate cancer (PbCre+Ptenfl /flKrasG12V and PbCre+Ptenfl /flp53fl/ fl ). In contrast, prostate epithelial cell-specific expression of wild-type (WT) Plexin-B1 in PbCre+Ptenfl /flKrasG12V mice significantly decreases metastasis, showing that a single clinically relevant Pro1597Leu amino-acid change converts Plexin-B1 from a metastasis-suppressor to a metastasis-promoter. Furthermore, PLXNB1P1597L significantly increased invasion of tumor cells into the prostate stroma, while PLXNB1WT reduced invasion, suggesting that Plexin-B1 has a role in the initial stages of metastasis. Deletion of RhoA/C or PDZRhoGEF in Ptenfl /flKrasG12VPLXNB1P1597L mice suppressed metastasis, implicating the Rho/ROCK pathway in this phenotypic switch. Germline deletion of Plexin-B1, to model anti-Plexin-B1 therapy, significantly decreased invasion and metastasis in both models. Our results demonstrate that Plexin-B1 plays a complex yet significant role in metastasis in mouse models of prostate cancer and is a potential therapeutic target to block the lethal spread of the disease. Significance: Few therapeutic targets have been identified specifically for preventing locally invasive/oligometastatic prostate cancer from becoming more widely disseminated. Our findings suggest Plexin-B1 signaling, particularly from the clinically relevant P1597L mutant, is such a target.


Assuntos
Antineoplásicos , Neoplasias da Próstata , Humanos , Masculino , Camundongos , Animais , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Receptores de Superfície Celular/genética , Transdução de Sinais/genética , Neoplasias da Próstata/genética , Camundongos Transgênicos
6.
Am J Sports Med ; 51(2): 367-378, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36661257

RESUMO

BACKGROUND: There are limited randomized controlled trials with long-term outcomes comparing autologous chondrocyte implantation (ACI) versus alternative forms of surgical cartilage management within the knee. PURPOSE: To determine at 5 years after surgery whether ACI was superior to alternative forms of cartilage management in patients after a failed previous treatment for chondral or osteochondral defects in the knee. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: In total, 390 participants were randomly assigned to receive either ACI or alternative management. Patients aged 18 to 55 years with one or two symptomatic cartilage defects who had failed 1 previous therapeutic surgical procedure in excess of 6 months prior were included. Dual primary outcome measures were used: (1) patient-completed Lysholm knee score and (2) time from surgery to cessation of treatment benefit. Secondary outcome measures included International Knee Documentation Committee and Cincinnati Knee Rating System scores, as well as number of serious adverse events. Analysis was performed on an intention-to-treat basis. RESULTS: Lysholm scores were improved by 1 year in both groups (15.4 points [95% CI, 11.9 to 18.8] and 15.2 points [95% CI, 11.6 to 18.9]) for ACI and alternative, with this improvement sustained over the duration of the trial. However, no evidence of a difference was found between the groups at 5 years (2.9 points; 95% CI, -1.8 to 7.5; P = .46). Approximately half of the participants (55%; 95% CI, 47% to 64% with ACI) were still experiencing benefit at 5 years, with time to cessation of treatment benefit similar in both groups (hazard ratio, 0.97; 95% CI, 0.72 to 1.32; P > .99). There was a differential effect on Lysholm scores in patients without previous marrow stimulation compared with those with marrow stimulation (P = .03; 6.4 points in favor of ACI; 95% CI, -0.4 to 13.1). More participants experienced a serious adverse event with ACI (P = .02). CONCLUSION: Over 5 years, there was no evidence of a difference in Lysholm scores between ACI and alternative management in patients who had previously failed treatment. Previous marrow stimulation had a detrimental effect on the outcome of ACI. REGISTRATION: International Standard Randomised Controlled Trial Number: 48911177.


Assuntos
Cartilagem Articular , Procedimentos Ortopédicos , Humanos , Cartilagem Articular/cirurgia , Condrócitos/transplante , Articulação do Joelho/cirurgia , Procedimentos Ortopédicos/métodos , Transplante Autólogo/métodos
7.
Front Psychol ; 13: 870090, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756314

RESUMO

Sporadic efforts have been made to introduce computational thinking methods into K-12 education in Palestine, but these have been held back by the challenging educational environment. However, a recent in-service training initiative, funded and organized by the Ministry or Education of Palestine, constitutes a significant effort to embed computational thinking in K-12 practice. The middle school teachers who participated in the training course were invited to participate in the present study, and 38 did so. A qualitative approach involving both interviews with teachers and classroom observations was used in data collection. All the teachers agreed to be observed in their classrooms, while 20 of the 38 also agreed to participate in the interviews. The findings showed that teachers of a range of topics, including social sciences and languages, employed computational thinking skills in teaching their students, but they were confronted by a number of challenges, including technical infrastructure and support, and a lack of time to prepare CT classes and space in the curriculum to deliver them. The results indicate that the most appropriate action to support teachers' delivery of CT would be to provide peer exchanges and expert coaching in the integration of CT in the curriculum.

8.
Nat Commun ; 13(1): 2416, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35504909

RESUMO

A multimer of retroviral integrase (IN) synapses viral DNA ends within a stable intasome nucleoprotein complex for integration into a host cell genome. Reconstitution of the intasome from the maedi-visna virus (MVV), an ovine lentivirus, revealed a large assembly containing sixteen IN subunits1. Herein, we report cryo-EM structures of the lentiviral intasome prior to engagement of target DNA and following strand transfer, refined at 3.4 and 3.5 Å resolution, respectively. The structures elucidate details of the protein-protein and protein-DNA interfaces involved in lentiviral intasome formation. We show that the homomeric interfaces involved in IN hexadecamer formation and the α-helical configuration of the linker connecting the C-terminal and catalytic core domains are critical for MVV IN strand transfer activity in vitro and for virus infectivity. Single-molecule microscopy in conjunction with photobleaching reveals that the MVV intasome can bind a variable number, up to sixteen molecules, of the lentivirus-specific host factor LEDGF/p75. Concordantly, ablation of endogenous LEDGF/p75 results in gross redistribution of MVV integration sites in human and ovine cells. Our data confirm the importance of the expanded architecture observed in cryo-EM studies of lentiviral intasomes and suggest that this organization underlies multivalent interactions with chromatin for integration targeting to active genes.


Assuntos
DNA Viral , Integrases , Animais , Humanos , Domínio Catalítico , DNA Viral/metabolismo , Integrases/metabolismo , Lentivirus/genética , Lentivirus/metabolismo , Modelos Moleculares , Retroviridae/genética , Ovinos/genética , Integração Viral
9.
Equine Vet J ; 54(1): 82-96, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33534938

RESUMO

BACKGROUND: Osteochondrosis occurs due to failure of the blood supply to growth cartilage. Osteochondrosis lesions have been identified in small tarsal bones and suggested to cause distal tarsal osteoarthritis; however, it has not been determined whether distal tarsal osteochondrosis lesions were the result of vascular failure. OBJECTIVES: To perform post-mortem arterial perfusion and micro-computed tomography (CT) of the central (CTB) and third tarsal bones (TIII) of fetuses and foals up to 5 months old, to describe tarsal development and any lesions detected. STUDY DESIGN: Descriptive, nonconsecutive case series. METHODS: Twenty-three animals that died or were euthanased from 228 days of gestation to 5 months old were collected, comprising two fetuses and nine foals of miscellaneous breeds and 12 Icelandic Horse foals, a breed with high prevalence of distal tarsal osteoarthritis. One hindlimb from each foal was perfused arterially with barium, and the CTB and TIII were examined with micro-CT. RESULTS: Perfusion yielded partial information from 41% of the animals. The CTB and TIII were supplied by nutrient arteries and perichondrial vessels with vertical, transverse and circumferential configurations. Fourteen of the 23 (61%) animals had focal defects in the ossification front, that is, radiological osteochondrosis. The majority of lesions matched the configuration and development of vertical vessels. Additionally, full-thickness, cylindrical defects matched transverse vessels, and the long axes of some dorsal lesions matched circumferential vessels. MAIN LIMITATIONS: Lack of histological validation. CONCLUSIONS: Post-mortem perfusion was poor for examination of the blood supply to the growth cartilage of the CTB and TIII. Radiological osteochondrosis lesions were compatible with vascular failure because they were focal, and because lesion geometry matched vessel configuration. The relationship between osteochondrosis and distal tarsal osteoarthritis warrants further investigation.


Assuntos
Doenças dos Cavalos , Osteoartrite , Osteocondrose , Ossos do Tarso , Animais , Tornozelo , Doenças dos Cavalos/diagnóstico por imagem , Cavalos , Osteoartrite/diagnóstico por imagem , Osteoartrite/etiologia , Osteoartrite/veterinária , Osteocondrose/diagnóstico por imagem , Osteocondrose/veterinária , Microtomografia por Raio-X
11.
Antibiotics (Basel) ; 10(2)2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33572497

RESUMO

Thailand spends $203 million on antibiotics every year, and patients can still access antimicrobials over the counter without a prescription. Community pharmacy plays a pivotal role in improving access and ensuring the appropriate use of antimicrobials. However, little is known about current practices in this setting. This study aims to assess Thai community pharmacists' knowledge, attitudes and practices (KAP) regarding antimicrobials' use and resistance. A cross-sectional study was conducted in Bangkok and Chonburi province in 2017 using an online self-administered questionnaire. The questionnaire was completed by 372 community pharmacists (71.4% response rate). The most commonly encountered infections in the community were upper and lower respiratory tract infections. The most commonly dispensed antimicrobials were broad-spectrum antibiotics including aminopenicillins and fluoroquinolones. Thai pharmacists have a good knowledge, attitude, and practice regarding antimicrobials' use and resistance. They dispense anti-microbials in line with local guidelines, although international guidelines may not indicate anti-biotics for viral self-limiting infections. While community pharmacy in Thailand could be the most accessible healthcare resource for patients, inappropriate provision of antimicrobials for self-limiting viral infections by pharmacists will increase antimicrobial resistance. This highlights the need for updated guidance and improved pharmacists' training.

12.
Proc Biol Sci ; 288(1942): 20202823, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33434457

RESUMO

The motion dazzle hypothesis posits that high contrast geometric patterns can cause difficulties in tracking a moving target and has been argued to explain the patterning of animals such as zebras. Research to date has only tested a small number of patterns, offering equivocal support for the hypothesis. Here, we take a genetic programming approach to allow patterns to evolve based on their fitness (time taken to capture) and thus find the optimal strategy for providing protection when moving. Our 'Dazzle Bug' citizen science game tested over 1.5 million targets in a touch screen game at a popular visitor attraction. Surprisingly, we found that targets lost pattern elements during evolution and became closely background matching. Modelling results suggested that targets with lower motion energy were harder to catch. Our results indicate that low contrast, featureless targets offer the greatest protection against capture when in motion, challenging the motion dazzle hypothesis.


Assuntos
Ciência do Cidadão , Percepção de Movimento , Animais , Movimento (Física) , Movimento
13.
Front Med Technol ; 3: 729658, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35047956

RESUMO

Objectives: The provision of high-quality personal protective equipment (PPE) has been a critical challenge during the COVID-19 pandemic. We evaluated an alternative strategy, mass deployment of a powered air-purifying respirator (PeRSo), in a large university hospital. Methods: We performed prospective user feedback via questionnaires sent to healthcare workers (HCWs) issued PeRSos, economic analysis, and evaluated the real-world impact. Results: Where paired responses were available, PeRSo was preferred over droplet precautions for comfort, patient response, overall experience, and subjective feeling of safety. For all responses, more participants reported the overall experience being rated "Very good" more frequently for PeRSo. The primary limitation identified was impairment of hearing. Economic simulation exercises revealed that the adoption of PeRSo within ICU is associated with net cost savings in the majority of scenarios and savings increased progressively with greater ITU occupancy. In evaluation during the second UK wave, over 3,600 respirators were deployed, all requested by staff, which were associated with a low staff absence relative to most comparator hospitals. Conclusions: Health services should consider a widespread implementation of powered reusable respirators as a safe and sustainable solution for the protection of HCWs as SARS-CoV-2 becomes an endemic viral illness.

14.
Equine Vet J ; 53(1): 134-142, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32144821

RESUMO

BACKGROUND: Growth cartilage is found in the articular-epiphyseal cartilage complex (AECC) and the physis. It has a temporary blood supply organised as end arteries. Vascular failure is associated with osteochondrosis, but infection can also obstruct vessels. The location of bacteria was recently compared to arterial perfusion, and the results indicated that they were located in the distal tips of AECC end arteries. Systematic perfusion studies were not available for comparison to the infected physes. Further studies may improve our understanding of infections and other pathologies. OBJECTIVES: To describe development of the blood supply to the growth cartilage of the medial femoral condyle in fetuses and foals from 228 days of gestation to 62 days old. STUDY DESIGN: Ex vivo arterial perfusion study. METHODS: The left medial femoral condyle of 10 Norwegian Fjord Pony fetuses and foals (228 days of gestation to 62 days old) and one Norwegian-Swedish Coldblooded Trotter foal (10 days old) was arterially perfused with barium and underwent micro-computed tomography, qualitative and quantitative description of vessels. RESULTS: In the fetus, the physis was supplied by metaphyseal-origin arteries. In 1-10 day-old foals, the physis was supplied by a mixture of metaphyseal- and epiphyseal-origin arteries, and from 15 days of age by epiphyseal-origin arteries only. The number of vessels increased before it decreased in both the AECC and the physis postnatally. Vessels in the cartilage showed a monopodial branching pattern, whereas vessels in epiphyseal and metaphyseal bone showed both monopodial and dichotomous branching. MAIN LIMITATIONS: Foals with confirmed pathologies were not examined. CONCLUSIONS: The blood supply to growth cartilage changed with age, including the physeal supply that changed from metaphyseal- to epiphyseal-origin arteries. The number of vessels increased before it decreased postnatally, and two different branching patterns were observed. These results may improve our understanding of growth cartilage vascular failure and osteomyelitis.


Assuntos
Doenças dos Cavalos , Osteocondrose , Animais , Cartilagem , Epífises , Fêmur , Lâmina de Crescimento , Cavalos , Osteocondrose/veterinária , Microtomografia por Raio-X
15.
Post Reprod Health ; 26(3): 155-161, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32997591

RESUMO

Vulval irritation and discomfort can be a common presentation to both primary and secondary care. These symptoms can become increasingly prevalent due to physiological changes, which occur to the female genitalia following menopausal transition or due to inflammatory conditions. The correct diagnosis and management can have a huge impact on the patients' quality of life. However, due to the nature of the symptoms, there can be delayed presentation to healthcare professionals. This article gives an overview of the most common benign vulval conditions in the post-menopausal woman, their clinical features and the diagnosis and initial management.


Assuntos
Exame Ginecológico/métodos , Administração dos Cuidados ao Paciente/métodos , Pós-Menopausa , Qualidade de Vida , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Líquen Plano/etiologia , Líquen Plano/fisiopatologia , Líquen Plano/psicologia , Líquen Plano/terapia , Prurido Vulvar/etiologia , Prurido Vulvar/fisiopatologia , Prurido Vulvar/psicologia , Prurido Vulvar/terapia , Líquen Escleroso Vulvar/etiologia , Líquen Escleroso Vulvar/fisiopatologia , Líquen Escleroso Vulvar/psicologia , Líquen Escleroso Vulvar/terapia
16.
J Fish Biol ; 97(4): 964-973, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32613622

RESUMO

Predator-prey size (PPS) relationships are determined by predator behaviour, with the likelihood of prey being eaten dependent on their size relative to that of the consumer. Published PPS relationships for 30 pelagic or benthic marine fish species were analysed using quantile regression to determine how median, lower and upper prey sizes varied with predator size and habitat. Habitat effects on predator foraging activity/mode, morphology, growth and natural mortality are quantified and the effects on PPS relationships explored. Pelagic species are more active, more likely to move by caudal fin propulsion and grow more rapidly but have higher mortality rates than benthic species, where the need for greater manoeuvrability when foraging in more physically complex habitats favours ambush predators using pectoral fin propulsion. Prey size increased with predator size in most species, but pelagic species ate relatively smaller prey than benthic predators. As pelagic predators grew, lower prey size limits changed little, and prey size range increased but median relative prey size declined, whereas the lower limit increased and median relative prey size was constant or increased in benthic species.


Assuntos
Organismos Aquáticos/fisiologia , Tamanho Corporal/fisiologia , Ecossistema , Peixes/anatomia & histologia , Peixes/fisiologia , Animais , Comportamento Predatório
17.
Eur J Med Genet ; 63(9): 103972, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32531461

RESUMO

Mutations in the TRIM8 gene have been described in patients with severe developmental delay, intellectual disability and epilepsy. Only six patients have been described to date. All the previous mutations were truncating variants clustered in the C-terminus of the protein. A previous patient with TRIM8-related epileptic encephalopathy was reported to have nephrotic syndrome. Here we describe the clinical, radiological and histological features of an 8-year-old male patient with a TRIM8 mutation who, in contrast to previous patients, had only mild intellectual disability and well-controlled epilepsy. The patient was found to have proteinuria at 2 years of age. Renal biopsy findings were suggestive of focal segmental glomerulosclerosis. His kidney function declined and peritoneal dialysis was started at 5 years of age. He underwent renal transplant at 7 years of age. Trio-based whole genome sequencing identified a novel de novo heterozygous frameshift mutation in TRIM8 (NM_030912.2) c.1198_1220del, p.(Tyr400ArgfsTer2). This patient is further evidence that TRIM8 mutations cause a syndrome with both neurological and renal features. Our findings suggest the spectrum of TRIM8-related disease may be wider than previously thought with the possibility of milder neurodevelopmental problems and/or a more severe, progressive renal phenotype. We highlight the need for proteinuria screening in patients with TRIM8 mutations.


Assuntos
Proteínas de Transporte/genética , Glomerulosclerose Segmentar e Focal/genética , Deficiência Intelectual/genética , Mutação , Proteínas do Tecido Nervoso/genética , Proteinúria/genética , Criança , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Deficiência Intelectual/patologia , Masculino , Proteinúria/patologia , Síndrome
18.
Artigo em Inglês | MEDLINE | ID: mdl-32205351

RESUMO

Resistance to amoxicillin-clavulanate, a widely used beta-lactam/beta-lactamase inhibitor combination antibiotic, is rising globally, and yet susceptibility testing remains challenging. To test whether whole-genome sequencing (WGS) could provide a more reliable assessment of susceptibility than traditional methods, we predicted resistance from WGS for 976 Escherichia coli bloodstream infection isolates from Oxfordshire, United Kingdom, comparing against phenotypes from the BD Phoenix (calibrated against EUCAST guidelines). A total of 339/976 (35%) isolates were amoxicillin-clavulanate resistant. Predictions based solely on beta-lactamase presence/absence performed poorly (sensitivity, 23% [78/339]) but improved when genetic features associated with penicillinase hyperproduction (e.g., promoter mutations and copy number estimates) were considered (sensitivity, 82% [277/339]; P < 0.0001). Most discrepancies occurred in isolates with MICs within ±1 doubling dilution of the breakpoint. We investigated two potential causes: the phenotypic reference and the binary resistant/susceptible classification. We performed reference standard, replicated phenotyping in a random stratified subsample of 261/976 (27%) isolates using agar dilution, following both EUCAST and CLSI guidelines, which use different clavulanate concentrations. As well as disagreeing with each other, neither agar dilution phenotype aligned perfectly with genetic features. A random-effects model investigating associations between genetic features and MICs showed that some genetic features had small, variable and additive effects, resulting in variable resistance classification. Using model fixed-effects to predict MICs for the non-agar dilution isolates, predicted MICs were in essential agreement (±1 doubling dilution) with observed (BD Phoenix) MICs for 691/715 (97%) isolates. This suggests amoxicillin-clavulanate resistance in E. coli is quantitative, rather than qualitative, explaining the poorly reproducible binary (resistant/susceptible) phenotypes and suboptimal concordance between different phenotypic methods and with WGS-based predictions.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio , Escherichia coli , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ácido Clavulânico/farmacologia , Escherichia coli/genética , Testes de Sensibilidade Microbiana , Fenótipo , Reino Unido , beta-Lactamases/genética
19.
BJU Int ; 125(4): 506-514, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31900963

RESUMO

OBJECTIVE: To test the hypothesis that the baseline clinico-pathological features of the men with localized prostate cancer (PCa) included in the ProtecT (Prostate Testing for Cancer and Treatment) trial who progressed (n = 198) at a 10-year median follow-up were different from those of men with stable disease (n = 1409). PATIENTS AND METHODS: We stratified the study participants at baseline according to risk of progression using clinical disease stage, pathological grade and PSA level, using Cox proportional hazard models. RESULTS: The findings showed that 34% of participants (n = 505) had intermediate- or high-risk PCa, and 66% (n = 973) had low-risk PCa. Of 198 participants who progressed, 101 (51%) had baseline International Society of Urological Pathology Grade Group 1, 59 (30%) Grade Group 2, and 38 (19%) Grade Group 3 PCa, compared with 79%, 17% and 5%, respectively, for 1409 participants without progression (P < 0.001). In participants with progression, 38% and 62% had baseline low- and intermediate-/high-risk disease, compared with 69% and 31% of participants with stable disease (P < 0.001). Treatment received, age (65-69 vs 50-64 years), PSA level, Grade Group, clinical stage, risk group, number of positive cores, tumour length and perineural invasion were associated with time to progression (P ≤ 0.005). Men progressing after surgery (n = 19) were more likely to have a higher Grade Group and pathological stage at surgery, larger tumours, lymph node involvement and positive margins. CONCLUSIONS: We demonstrate that one-third of the ProtecT cohort consists of people with intermediate-/high-risk disease, and the outcomes data at an average of 10 years' follow-up are generalizable beyond men with low-risk PCa.


Assuntos
Neoplasias da Próstata/patologia , Idoso , Estudos de Coortes , Progressão da Doença , Seguimentos , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Medição de Risco , Fatores de Tempo
20.
Am Psychol ; 74(8): 940-953, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31697129

RESUMO

This article charts the historical period from the 1950s to the 1990s, focusing on the role of Psychology in the lives of lesbian, gay, bisexual, trans, intersex and queer (LGBTIQ) people in Britain. Psychology has been, and is, central to the social, legal, and medical understandings of biological sex and how best to understand diversity in gender and sexuality. Likewise, gay liberation and liberationist politics also had an effect on Psychology. For the 1950s to 1960s, we outline how psychologists influenced the law in relation to the Wolfenden Report (1957) and how expertise was centrally located within the 'psy' disciplines. Following this, in the 1960s to 1970s, activists began to challenge this expertise and became increasingly critical of pathologization and of 'treatments' for homosexuality. They did not reject Psychology wholesale, however, and some groups engaged with queer affirmative psychologists who had similar liberatory aims. Finally, for the 1980s to 1998, we highlight the establishment of the Lesbian and Gay Section of the British Psychological Society, which signaled institutional recognition of lesbian and gay psychologists. This is explored against a backdrop of a specific British history of HIV/AIDS and Section 28. The past 50 years have been a battleground of categories in which LGBTIQ people were conflated, compared, and confused. We demonstrate that psychologists (not all of whom adopted a pathologizing perspective), alongside politicians, lawyers, doctors, journalists, and activists, all played a role in the boundary-making practices of this period. Across this entangled history, we demonstrate varied and significant shifts in the legitimacy of professional and personal expertise. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Psicologia/história , Minorias Sexuais e de Gênero/história , Minorias Sexuais e de Gênero/psicologia , Sexualidade/história , Feminino , História do Século XX , Humanos , Masculino , Política , Minorias Sexuais e de Gênero/legislação & jurisprudência , Sexualidade/psicologia , Reino Unido
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA