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Mantle plumes are buoyant upwellings of hot rock that transport heat from Earth's core to its surface, generating anomalous regions of volcanism that are not directly associated with plate tectonic processes. The best-studied example is the Hawaiian-Emperor chain, but the emergence of two sub-parallel volcanic tracks along this chain, Loa and Kea, and the systematic geochemical differences between them have remained unexplained. Here we argue that the emergence of these tracks coincides with the appearance of other double volcanic tracks on the Pacific plate and a recent azimuthal change in the motion of the plate. We propose a three-part model that explains the evolution of Hawaiian double-track volcanism: first, mantle flow beneath the rapidly moving Pacific plate strongly tilts the Hawaiian plume and leads to lateral separation between high- and low-pressure melt source regions; second, the recent azimuthal change in Pacific plate motion exposes high- and low-pressure melt products as geographically distinct volcanoes, explaining the simultaneous emergence of double-track volcanism across the Pacific; and finally, secondary pyroxenite, which is formed as eclogite melt reacts with peridotite, dominates the low-pressure melt region beneath Loa-track volcanism, yielding the systematic geochemical differences observed between Loa- and Kea-type lavas. Our results imply that the formation of double-track volcanism is transitory and can be used to identify and place temporal bounds on plate-motion changes.
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PURPOSE OF REVIEW: We review recent evidence on the use of neuromodulation for treating eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge eating disorder. We evaluate studies on (a) modern non-invasive methods of brain stimulation, such as transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), (b) electroconvulsive therapy (ECT) and (c) more invasive techniques, including deep brain stimulation (DBS). RECENT FINDINGS: Most reports on the clinical applications of neuromodulation in EDs are limited to case studies, case series and small clinical trials. The majority have focused on severe, enduring and hard-to-treat cases of AN. In this population, data suggest that both rTMS and DBS have therapeutic potential and are safe and acceptable. High-quality clinical trials in different ED populations are needed which investigate different stimulation methods, sites and parameters, the use of neuromodulation as stand-alone and/or adjunctive treatment, as well as the mechanisms of action.
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Anorexia Nervosa , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Estimulação Transcraniana por Corrente Contínua , Anorexia Nervosa/terapia , Bulimia Nervosa/terapia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Estimulação Magnética Transcraniana/métodosRESUMO
Seaweeds form the second largest global aquaculture product in volume, and despite rapid growth of the sector over the last 25 years, production and quality in top producing regions is becoming increasingly limited due to disease and pest outbreaks, the spread of non-native cultivars and the degradation of genetic health due to inbreeding. Most notably, the lack of biosecurity measures leading to disease and pest outbreaks are reported to cause the most significant production losses in the seaweed industry. This study uses the Knowledge, Attitude and Practice (KAP) survey tool to quantify and compare biosecurity cross-culturally, in two major red seaweed producing countries, the Philippines and Tanzania. Both countries have significantly different political contexts and the seaweed sector sits within two very different value chains. Seaweed-based commodities from these countries, however, enters the same international market for carrageenan, a thickening agent used for a variety of products globally. This study uses the KAP survey tool to assess currently-adopted biosecurity control measures and understand how potential policy strategies could be developed on an international scale. Farmers from both producing countries have good biosecurity knowledge. In Tanzania 64% farmers scored Fair or Good, and in the Philippines this was 95%. Corresponding scores in practices were lower, 85% Poor for Tanzania, and 88% Fair for the Philippines, indicating there is a lack of resources for farmers to implement additional practices. The information gathered using the KAP tool in the context of the global seaweed industry can be used to facilitate compromise between science, policy and practice whilst taking into consideration smaller-scale regional challenges. Given the results from the seaweed industry were similar to that of smallholder agricultural sectors, it is suggested that governmental programs to incentivise biosecurity in smallholder rural agriculture could be adapted for the seaweed industry. This study also demonstrates the potential use of the KAP survey, as a tool to accurately compare biosecurity challenges faced by farmers in different aquaculture sectors globally, and to encourage alignment in international approaches to aquaculture biosecurity policies.
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Criação de Animais Domésticos , Alga Marinha , Aquicultura , Biosseguridade , Fazendeiros , HumanosRESUMO
Hotspots are anomalous regions of volcanism at Earth's surface that show no obvious association with tectonic plate boundaries. Classic examples include the Hawaiian-Emperor chain and the Yellowstone-Snake River Plain province. The majority are believed to form as Earth's tectonic plates move over long-lived mantle plumes: buoyant upwellings that bring hot material from Earth's deep mantle to its surface. It has long been recognized that lithospheric thickness limits the rise height of plumes and, thereby, their minimum melting pressure. It should, therefore, have a controlling influence on the geochemistry of plume-related magmas, although unambiguous evidence of this has, so far, been lacking. Here we integrate observational constraints from surface geology, geochronology, plate-motion reconstructions, geochemistry and seismology to ascertain plume melting depths beneath Earth's longest continental hotspot track, a 2,000-kilometre-long track in eastern Australia that displays a record of volcanic activity between 33 and 9 million years ago, which we call the Cosgrove track. Our analyses highlight a strong correlation between lithospheric thickness and magma composition along this track, with: (1) standard basaltic compositions in regions where lithospheric thickness is less than 110 kilometres; (2) volcanic gaps in regions where lithospheric thickness exceeds 150 kilometres; and (3) low-volume, leucitite-bearing volcanism in regions of intermediate lithospheric thickness. Trace-element concentrations from samples along this track support the notion that these compositional variations result from different degrees of partial melting, which is controlled by the thickness of overlying lithosphere. Our results place the first observational constraints on the sub-continental melting depth of mantle plumes and provide direct evidence that lithospheric thickness has a dominant influence on the volume and chemical composition of plume-derived magmas.
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PURPOSE: Variations in substrate metabolism have been identified in women during continuous steady-state aerobic exercise performed at the same relative intensity throughout discrete phases of the menstrual cycle, although some evidence exists that this is abolished when carbohydrate is ingested. This investigation examined the effects of a supraphysiologic exogenous glucose infusion protocol, administered during two phases of the menstrual cycle (follicular and luteal) in eumenorrheic women to identify differences between metabolic, hormonal and substrate oxidative responses. METHODS: During the experimental conditions, blood glucose was infused intravenously at rates to "clamp" blood glucose at 10 mM in seven healthy females (age 20 ± 1 y, mass 55.0 ± 4.1 kg, [Formula: see text] 40.0 ± 1.8 ml/kg/min). Following 30 min of seated rest, participants exercised on a cycle ergometer for 90 min at 60% [Formula: see text]. During the rest period and throughout exercise, blood metabolites and hormones were collected at regular intervals, in addition to expired air for the measurement of substrate oxidation. RESULTS: Significant differences between ovarian hormones and menstrual phase were identified, with estrogen significantly higher during the luteal phase compared to the follicular phase (213.28 ± 30.70 pmol/l vs 103.86 ± 13.85 pmol/l; p = 0.016), and for progesterone (14.23 ± 4.88 vs 2.11 ± 0.36 nmol/l; p = 0.042). However, no further significance was identified in any of the hormonal, metabolite or substrate utilisation patterns between phases. CONCLUSION: These data demonstrate that the infusion of a supraphysiological glucose dose curtails any likely metabolic influence employed by the fluctuation of ovarian hormones in eumenorrheic women during moderate exercise.
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Exercício Físico/fisiologia , Glucose/administração & dosagem , Hormônios/metabolismo , Hiperglicemia/fisiopatologia , Ciclo Menstrual/fisiologia , Feminino , Humanos , Consumo de Oxigênio/fisiologia , Adulto JovemRESUMO
BACKGROUND: Young age at diagnosis for breast cancer raises the question of genetic susceptibility. We explored breast cancer susceptibility genes testing on ≤40-year-old patients with HER2-amplified invasive breast cancer. PATIENTS AND METHODS: Patients were selected from a large UK cohort study. The inclusion criterion was age ≤40 at diagnosis with confirmed HER2-amplified breast cancer. The probability of finding a BRCA gene mutation was calculated based on family history. Genetic testing used was either clinical testing for BRCA1 and BRCA2, with a subset also tested for TP53 mutations, or research-based testing using a typical panel comprising 17 breast cancer susceptibility genes (CSGs) including BRCA1, BRCA2 and TP53. RESULTS: Of the 591 eligible patients, clinical testing results were available for 133 cases and an additional 263 cases had panel testing results. BRCA testing across 396 cases found 8 BRCA2 (2%) and 6 BRCA1 (2%) pathogenic mutations. Of the 304 patients tested for TP53 mutations, overall 9 (3%) had deleterious TP53 mutations. Of the 396 patients, 101 (26%) met clinical criteria for BRCA testing (≥10% probability), among whom 11% had pathogenic BRCA mutations (6 BRCA2, 5 BRCA1). Where the probability was calculated to be <10%, only 4 of 295 (1%) patients had BRCA mutations. Among the 59 patients who had TP53 testing meeting the 10% threshold, 7 had mutations (12%). Likely functionally deleterious mutations in 14 lower penetrance CSGs were present in 12 of 263 (5%) panel-tested patients. CONCLUSION: Patients aged <41 at diagnosis with HER2+ breast cancer and no family history of breast cancer can be reassured that they have a low chance of being a high-risk gene carrier. If there is a strong family history, not only BRCA but also TP53 gene testing should be considered. The clinical utility of testing lower penetrance CSGs remains unclear.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença , Testes Genéticos , Receptor ErbB-2/genética , Proteína Supressora de Tumor p53/genética , Adulto , Feminino , Humanos , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. PATIENTS AND METHODS: This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. RESULTS: Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. CONCLUSION: These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. CLINICAL TRIALS NUMBER: Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493.
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Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Nitrilas/administração & dosagem , Triazóis/administração & dosagem , Idoso , Inibidores da Aromatase/administração & dosagem , Austrália , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Letrozol , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Pós-Menopausa , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Tamoxifeno/administração & dosagem , Resultado do TratamentoRESUMO
Maori women have one of the highest incidences of breast cancer in the world. This high incidence is generally unexplained although higher rates of obesity and alcohol intake are modifiable risk factors that may be important. Maori women are less likely to attend mammographic breast screening and are likely to be diagnosed with more advanced disease. This is one of the reasons for the excess mortality. Another factor is differences in the treatment pathway. Maori women are more likely to experience delay in receiving treatment, are less likely to receive radiotherapy, are more likely to be treated with a mastectomy and are less likely to adhere to long-term adjuvant endocrine therapy. However, genetic factors in Maori women do not seem to impact significantly on mortality. This review looks at the inequity between Maori and non-Maori women and addresses the causes. It proposes ways of reducing inequity through primary prevention, increased participation in breast screening and greater standardisation of the treatment pathway for women newly diagnosed with breast cancer. We believe that health system improvements will decrease barriers to health care participation for Maori women and suggest that further research into identifying and modifying obstacles within health systems is required.
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Consumo de Bebidas Alcoólicas/etnologia , Neoplasias da Mama/etnologia , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/etnologia , Mamografia/estatística & dados numéricos , Havaiano Nativo ou Outro Ilhéu do Pacífico , Obesidade/etnologia , População Branca , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Quimioterapia Adjuvante/estatística & dados numéricos , Diagnóstico Tardio , Detecção Precoce de Câncer , Feminino , Humanos , Incidência , Mastectomia/estatística & dados numéricos , Nova Zelândia/epidemiologia , Radioterapia Adjuvante/estatística & dados numéricos , Fatores de Risco , Tempo para o Tratamento/estatística & dados numéricosRESUMO
Identifying individuals with a genetic predisposition to developing familial colorectal cancer (CRC) is crucial to the management of the affected individual and their family. In order to do so, the physician requires an understanding of the different gene mutations and clinical manifestations of familial CRC. This review summarises the genetics, clinical manifestations and management of the known familial CRC syndromes, specifically Lynch syndrome, familial adenomatous polyposis, MUTYH-associated neoplasia, juvenile polyposis syndrome and Peutz-Jeghers syndrome. An individual suspected of having a familial CRC with an underlying genetic predisposition should be referred to a familial cancer centre to enable pre-test counselling and appropriate follow up.
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Polipose Adenomatosa do Colo/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais/epidemiologia , Predisposição Genética para Doença/epidemiologia , Polipose Intestinal/congênito , Síndromes Neoplásicas Hereditárias/epidemiologia , Síndrome de Peutz-Jeghers/epidemiologia , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Austrália/epidemiologia , Quimioprevenção/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Feminino , Aconselhamento Genético , Testes Genéticos , Humanos , Polipose Intestinal/diagnóstico , Polipose Intestinal/epidemiologia , Polipose Intestinal/genética , Masculino , Mutação/genética , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Nova Zelândia/epidemiologia , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/genética , PrevalênciaRESUMO
OBJECTIVES: The aim of this study is to identify key characteristics associated with mortality from breast cancer among women with newly diagnosed breast cancer in New Zealand (NZ). STUDY DESIGN: Case-control study. METHODS: All primary breast cancers diagnosed between 01/01/2002 and 31/12/2010 in Waikato, NZ, were identified from the Waikato Breast Cancer Register. A total of 258 breast cancer deaths were identified from 1767 invasive cancers diagnosed over this period. RESULTS: Breast cancer deaths (n = 246) were compared with an age and year of diagnosis matched control group (n = 652) who were alive at the time of the death of the corresponding case and subsequently did not die from breast cancer. Diagnosis through symptomatic presentation, advanced stage, higher grade, absent hormone receptors (i.e. oestrogen and progesterone) and HER-2 amplification were associated with significantly higher risks of breast cancer mortality in bivariate analysis. Tumour stage, grade and hormone receptor status remained significant in the multivariable model, while mode of detection and HER-2 status were non-significant. In the bivariate analysis, Maori women had a higher risk of breast cancer mortality compared to NZ European women (OR 1.34) which was statistically non-significant. However in the adjusted model, risk of mortality was lower for Maori compared to NZ European women, although this was not significant statistically (OR 0.85). CONCLUSIONS: Mortality pattern from breast cancer in this study were associated with established risk factors. Ethnic inequity in breast cancer mortality in NZ appears to be largely attributable to delay in diagnosis and tumour related factors. Further research in a larger cohort is needed to identify the full impact of these factors on ethnic inequity in breast cancer mortality.
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Neoplasias da Mama/etnologia , Neoplasias da Mama/mortalidade , Disparidades nos Níveis de Saúde , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , População Branca/estatística & dados numéricos , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Diagnóstico Tardio , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nova Zelândia/epidemiologia , Sistema de Registros , Medição de Risco , Fatores de RiscoRESUMO
In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8(+) T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20-30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5-10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients.
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Linfócitos T CD4-Positivos/imunologia , Varicela/etiologia , Linfopenia/etiologia , Mutação , Receptores de Interleucina-7/genética , Rubéola (Sarampo Alemão)/etiologia , Imunodeficiência Combinada Severa/genética , Vacinação/efeitos adversos , Variações do Número de Cópias de DNA , Exoma , Feminino , Humanos , Lactente , Análise de Sequência com Séries de Oligonucleotídeos , Imunodeficiência Combinada Severa/imunologiaRESUMO
We asked whether specific inspiratory muscle training (IMT) improves respiratory structure and function and peak exercise responses in highly trained athletes with cervical spinal cord injury (SCI). Ten Paralympic wheelchair rugby players with motor-complete SCI (C5-C7) were paired by functional classification then randomly assigned to an IMT or placebo group. Diaphragm thickness (B-mode ultrasonography), respiratory function [spirometry and maximum static inspiratory (PI ,max ) and expiratory (PE ,max ) pressures], chronic activity-related dyspnea (Baseline and Transition Dyspnea Indices), and physiological responses to incremental arm-crank exercise were assessed before and after 6 weeks of pressure threshold IMT or sham bronchodilator treatment. Compared to placebo, the IMT group showed significant increases in diaphragm thickness (P = 0.001) and PI ,max (P = 0.016). There was a significant increase in tidal volume at peak exercise in IMT vs placebo (P = 0.048) and a strong trend toward an increase in peak work rate (P = 0.081, partial eta-squared = 0.33) and peak oxygen uptake (P = 0.077, partial eta-squared = 0.34). No other indices changed post-intervention. In conclusion, IMT resulted in significant diaphragmatic hypertrophy and increased inspiratory muscle strength in highly trained athletes with cervical SCI. The strong trend, with large observed effect, toward an increase in peak aerobic performance suggests IMT may provide a useful adjunct to training in this population.
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Exercícios Respiratórios , Exercício Físico/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Adulto , Vértebras Cervicais , Diafragma/anatomia & histologia , Diafragma/diagnóstico por imagem , Dispneia/fisiopatologia , Teste de Esforço , Feminino , Futebol Americano/fisiologia , Humanos , Masculino , Força Muscular , Músculo Esquelético/fisiopatologia , Consumo de Oxigênio , Esportes para Pessoas com Deficiência , Volume de Ventilação Pulmonar , Ultrassonografia , Adulto JovemRESUMO
Breast cancer is the most common cancer to affect New Zealand women. Women diagnosed face several decisions regarding surgical treatment, including whether to undergo lumpectomy, mastectomy, or breast reconstruction. Reconstructive surgery adds an additional layer of complexity, with several reconstructive options, each associated with differing surgical and recovery times. Furthermore, surgical decisions are often made under time-pressure and significant diagnostic distress, therefore provision of good information to support decision-making is crucial to adequately inform women of their options. We interviewed 24 women who had undergone breast surgery within the preceding 12 months to assess the key factors leading to their decision to opt for their chosen surgical procedure. Interviews revealed that decision-making was complex and involved multiple factors. Women were ultimately confronted with assessing feminine identity versus survival. Whether opting for breast reconstruction or not, women were fearful of what surgery would involve and how their reconstructed breast or mastectomy scar might look following surgery. Shared decision-making between patient and clinician can mitigate this fear and provide women with a sense of autonomy over their health decisions. Provision of visual depictions of surgical outcomes was not routinely provided to those interviewed but was expressed as important to help women manage surgical expectations. Therefore our findings support the multi-modal presentation of diagnostic and treatment information to support decision-making. Likewise, women reported feeling unsupported in their decision not to undergo breast reconstruction, suggesting a need to develop resources to provide women with positive discussions about 'going flat'.
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Neoplasias da Mama , Mamoplastia , Feminino , Humanos , Mastectomia , Neoplasias da Mama/cirurgia , Tomada de Decisões , Mastectomia SegmentarRESUMO
In recent years, a growing body of literature on seafloor macro-litter has been produced worldwide. However, the spatial coverage of these studies is still limited and highly unbalanced, resulting in considerable knowledge gaps in some regions. To address this lack of information in Oceania, we extracted data from the Citizen Science project Dive Against Debris® to characterize marine debris collected by volunteer scuba divers on the coastal seafloor. Overall, the average litter density was 58.22 items/100m2, with plastics accounting for approximately 50 % of the total abundance and Single Use Plastics accounting for nearly 17 %. Notably, 36 % of the total litter abundance consisted of lost Fishing Gear including fishing lines, sinkers, baits and hooks as the most abundant debris items. To reduce lost fishing gear, clean-up initiatives by divers along with management actions such as education programs for fishermen, gear restrictions and the identification of designated fishing sites are recommended.
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Ciência do Cidadão , Mergulho , Humanos , Monitoramento Ambiental/métodos , Resíduos/análise , PlásticosRESUMO
BACKGROUND: Aromatase inhibitors are the preferred adjuvant endocrine therapy for the majority of postmenopausal women with hormone-responsive early breast cancer. Although generally more effective than tamoxifen, aromatase inhibitor therapy is associated with increased bone loss and fracture risk. PATIENTS AND METHODS: Postmenopausal women receiving adjuvant letrozole (2.5 mg/day for 5 years; N = 1065) were randomly assigned to immediate zoledronic acid (zoledronate) 4 mg every 6 months for 5 years, or delayed zoledronate (initiated for fracture or on-study bone mineral density [BMD] decrease). The primary end point was the change in lumbar spine BMD at 12 months. Lumbar spine and total hip BMD at subsequent follow-up, disease-free survival (DFS), and overall survival were assessed as secondary end points. RESULTS: At 60 months (final analysis), the mean change in lumbar spine BMD was +4.3% with immediate zoledronate and -5.4% with delayed intervention (P < 0.0001). Immediate zoledronate reduced the risk of DFS events by 34% (hazard ratio [HR] = 0.66; P = 0.0375) with fewer local (0.9% versus 2.3%) and distant (5.5% versus 7.7%) recurrences versus delayed zoledronate. In the delayed group, delayed initiation of zoledronate substantially improved DFS versus no zoledronate (HR = 0.46; P = 0.0334). CONCLUSIONS: Immediate zoledronate in postmenopausal women receiving letrozole preserved BMD and is associated with improved DFS compared with letrozole alone. Clinical Trials Registration No NCT00171340.
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Antineoplásicos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Nitrilas/uso terapêutico , Triazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias da Mama/fisiopatologia , Quimioterapia Adjuvante , Difosfonatos/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Imidazóis/efeitos adversos , Letrozol , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/metabolismo , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Pós-Menopausa , Triazóis/efeitos adversos , Ácido ZoledrônicoRESUMO
VLS-grown semiconductor nanowires have emerged as a viable prospect for future solar-based energy applications. In this paper, we report highly efficient charge separation and collection across in situ doped Si p-n junction nanowires with a diameter <100 nm grown in a cold wall CVD reactor. Our photoexcitation measurements indicate an internal quantum efficiency of ~50%, whereas scanning photocurrent microscopy measurements reveal effective minority carrier diffusion lengths of ~1.0 µm for electrons and 0.66 µm for holes for as-grown Si nanowires (d(NW) ≈ 65-80 nm), which are an order of magnitude larger than those previously reported for nanowires of similar diameter. Further analysis reveals that the strong suppression of surface recombination is mainly responsible for these relatively long diffusion lengths, with surface recombination velocities (S) calculated to be 2 orders of magnitude lower than found previously for as-grown nanowires, all of which used hot wall reactors. The degree of surface passivation achieved in our as-grown nanowires is comparable to or better than that achieved for nanowires in prior studies at significantly larger diameters. We suggest that the dramatically improved surface recombination velocities may result from the reduced sidewall reactions and deposition in our cold wall CVD reactor.
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The gene ST7 has recently been implicated as the broad-range tumor suppressor on human chromosome 7q31.1. We did not detect somatic mutations in ST7 in any of 149 primary ovarian, breast or colon carcinomas. These data suggest that epigenetic downregulation or haploinsufficiency, rather than somatic genetic alterations, may be the primary mechanism of abrogation of ST7 function in these tumor types.
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Neoplasias da Mama/genética , Cromossomos Humanos Par 7 , Genes Supressores de Tumor , Proteínas de Membrana/genética , Mutação , Neoplasias Ovarianas/genética , Neoplasias Colorretais , Feminino , HumanosRESUMO
Mammographic density (MD) is the area of breast tissue that appears radiologically white on mammography. Although high MD is a strong risk factor for breast cancer, independent of BRCA1/2 mutation status, the molecular basis of high MD and its associated breast cancer risk is poorly understood. MD studies will benefit from an animal model, where hormonal, gene and drug perturbations on MD can be measured in a preclinical context. High and low MD tissues were selectively sampled by stereotactic biopsy from operative specimens of high-risk women undergoing prophylactic mastectomy. The high and low MD tissues were transferred into separate vascularised biochambers in the groins of SCID mice. Chamber material was harvested after 6 weeks for histological analyses and immunohistochemistry for cytokeratins, vimentin and a human-specific mitochondrial antigen. Within-individual analysis was performed in replicate mice, eliminating confounding by age, body mass index and process-related factors, and comparisons were made to the parental human tissue. Maintenance of differential MD post-propagation was assessed radiographically. Immunohistochemical staining confirmed the preservation of human glandular and stromal components in the murine biochambers, with maintenance of radiographic MD differential. Propagated high MD regions had higher stromal (p = 0.0002) and lower adipose (p = 0.0006) composition, reflecting the findings in the original human breast tissue, although glands appeared small and non-complex in both high and low MD groups. No significant differences were observed in glandular area (p = 0.4) or count (p = 0.4) between high and low MD biochamber tissues. Human mammary glandular and stromal tissues were viably maintained in murine biochambers, with preservation of differential radiographic density and histological features. Our study provides a murine model for future studies into the biomolecular basis of MD as a risk factor for breast cancer.
Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Mamografia , Engenharia Tecidual , Animais , Mama/fisiologia , Mama/transplante , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Camundongos , Camundongos SCID , Células Estromais , Transplante de Tecidos , Transplante HeterólogoRESUMO
This study was designed to investigate the effect of ingesting a glucose plus fructose solution on the metabolic responses to soccer-specific exercise in the heat and the impact on subsequent exercise capacity. Eleven male soccer players performed a 90 min soccer-specific protocol on three occasions. Either 3 ml · kg(-1) body mass of a solution containing glucose (1 g · min(-1) glucose) (GLU), or glucose (0.66 g · min(-1)) plus fructose (0.33 g · min(-1)) (MIX) or placebo (PLA) was consumed every 15 minutes. Respiratory measures were undertaken at 15-min intervals, blood samples were drawn at rest, half-time and on completion of the protocol, and muscle glycogen concentration was assessed pre- and post-exercise. Following the soccer-specific protocol the Cunningham and Faulkner test was performed. No significant differences in post-exercise muscle glycogen concentration (PLA, 62.99 ± 8.39 mmol · kg wet weight(-1); GLU 68.62 ± 2.70; mmol · kg wet weight(-1) and MIX 76.63 ± 6.92 mmol · kg wet weight(-1)) or exercise capacity (PLA, 73.62 ± 8.61 s; GLU, 77.11 ± 7.17 s; MIX, 83.04 ± 9.65 s) were observed between treatments (P > 0.05). However, total carbohydrate oxidation was significantly increased during MIX compared with PLA (P < 0.05). These results suggest that when ingested in moderate amounts, the type of carbohydrate does not influence metabolism during soccer-specific intermittent exercise or affect performance capacity after exercise in the heat.
Assuntos
Desempenho Atlético/fisiologia , Metabolismo dos Carboidratos/efeitos dos fármacos , Dieta/métodos , Exercício Físico/fisiologia , Temperatura Alta , Monossacarídeos/farmacologia , Futebol/fisiologia , Adulto , Sacarose Alimentar/farmacologia , Combinação de Medicamentos , Frutose/farmacologia , Glucose/farmacologia , Glicogênio/metabolismo , Humanos , Masculino , Músculo Esquelético/fisiologia , Oxirredução , Aptidão FísicaRESUMO
BACKGROUND: Younger women (defined as those < 50 years who are likely pre-menopausal at time of diagnosis) with breast cancer often experience persistent treatment-related side effects that adversely affect their physical and psychological wellbeing. The Women's Wellness After Cancer Program (WWACP) was adapted and piloted in Australia to address these outcomes in younger women. The aims of this feasibility study are to determine (1) the potential to translate the Younger WWACP (YWWACP) intervention to a broader population base in Aotearoa/New Zealand and Australia, and (2) the potential for success of a larger, international, phase ΙΙΙ, randomised controlled trial. METHODS: This bi-national, randomised, single-blinded controlled trial involves two main study sites in Aotearoa/New Zealand (Kowhai study) and Australia (EMERALD study). Young women aged 18 to 50 years who completed intensive treatment (surgery, chemotherapy, and/or radiotherapy) for breast cancer in the previous 24 months are eligible. The potential to translate the YWWACP to women in these two populations will be assessed according to several feasibility outcomes. These include examining intervention accessibility, acceptability and uptake; intervention sustainability and adherence; the prevalence components of the intervention in the control group; intervention efficacy; participants' perception of measurement burden; the effectiveness of planned recruitment strategies; and trial methods and procedures. The studies collectively aim to enrol 60 participants in the intervention group and 60 participants in the control group (total = 120 participants). DISCUSSION: Ethical approval has been received from the Southern Health and Disability Ethics Committee (Kowhai ref: 19/STH/215), and UnitingCare Human Research Ethics Committee (EMERALD ref: 202103). This study will provide important data on the feasibility of the refined YWWACP in the trans-Tasman context. This study will account for and harmonise cross-country differences to ensure the success of a proposed international grant application for a phase ΙΙΙ randomised controlled trial of this program to improve outcomes in younger women living with breast cancer. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): Kowhai ACTRN12620000260921 , registered on 27 February 2020. EMERALD ACTRN12621000447853 , registered on 19 April 2021.