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1.
Hum Mol Genet ; 31(24): 4286-4294, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-35925860

RESUMO

The complex pathogenesis of rheumatoid arthritis (RA) is not fully understood, with few studies exploring the genomic contribution to RA in patients from Africa. We report a genome-wide association study (GWAS) of South-Eastern Bantu-Speaking South Africans (SEBSSAs) with seropositive RA (n = 531) and population controls (n = 2653). Association testing was performed using PLINK (logistic regression assuming an additive model) with sex, age, smoking and the first three principal components as covariates. The strong association with the Human Leukocyte Antigen (HLA) region, indexed by rs602457 (near HLA-DRB1), was replicated. An additional independent signal in the HLA region represented by the lead SNP rs2523593 (near the HLA-B gene; Conditional P-value = 6.4 × 10-10) was detected. Although none of the non-HLA signals reached genome-wide significance (P < 5 × 10-8), 17 genomic regions showed suggestive association (P < 5 × 10-6). The GWAS replicated two known non-HLA associations with MMEL1 (rs2843401) and ANKRD55 (rs7731626) at a threshold of P < 5 × 10-3 providing, for the first time, evidence for replication of non-HLA signals for RA in sub-Saharan African populations. Meta-analysis with summary statistics from an African-American cohort (CLEAR study) replicated three additional non-HLA signals (rs11571302, rs2558210 and rs2422345 around KRT18P39-NPM1P33, CTLA4-ICOS and AL645568.1, respectively). Analysis based on genomic regions (200 kb windows) further replicated previously reported non-HLA signals around PADI4, CD28 and LIMK1. Although allele frequencies were overall strongly correlated between the SEBSSA and the CLEAR cohort, we observed some differences in effect size estimates for associated loci. The study highlights the need for conducting larger association studies across diverse African populations to inform precision medicine-based approaches for RA in Africa.


Assuntos
Artrite Reumatoide , Estudo de Associação Genômica Ampla , Antígenos HLA , Humanos , Artrite Reumatoide/genética , Predisposição Genética para Doença , Antígenos HLA/genética , Cadeias HLA-DRB1/genética , Quinases Lim/genética , Polimorfismo de Nucleotídeo Único , África do Sul
2.
Diabet Med ; 40(9): e15126, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37171467

RESUMO

AIMS: Use of the CamAPS FX hybrid closed loop (CL) system is associated with improved time in range and glycated haemoglobin A1c across the age span, but little is known about its effects on patient-reported outcomes (PROs). METHODS: This open-label, randomized, multi-site study compared CamAPS FX to sensor-augmented pump (SAP) in a sample of older adults (≥60 years) with type 1 diabetes (T1D). Thirty-five older adults completed PROs surveys at the start of the study and after each period of 16 weeks using either CL or SAP. At the end of the study, 19 participated in interviews about their experiences with CL. RESULTS: Results examining the 16 weeks of CL use showed that the overall Diabetes Distress Scale score and two subscales (powerlessness and physician distress) improved significantly along with trust on the Glucose Monitoring Satisfaction Survey. User experience interview responses were consistent in noting benefits of 'improved glycaemic control' and 'worrying less about diabetes'. CONCLUSION: In this sample of older adults with T1D who have previously shown glycaemic benefit, there are indicators of improved PROs and subjective user experience benefits.


Assuntos
Diabetes Mellitus Tipo 1 , Idoso , Humanos , Glicemia , Automonitorização da Glicemia/métodos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Resultado do Tratamento , Pessoa de Meia-Idade
3.
Environ Sci Technol ; 57(44): 16823-16833, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37874250

RESUMO

Haloacetaldehydes (HALs) represent the third-largest category of disinfection byproducts (DBPs) in drinking water in terms of weight. As a subset of unregulated DBPs, only a few HALs have undergone assessment, yielding limited information regarding their genotoxicity mechanisms. Herein, we developed a simplified yeast-based toxicogenomics assay to evaluate the genotoxicity of five specific HALs. This assay recorded the protein expression profiles of eight Saccharomyces cerevisiae strains fused with green fluorescent protein, including all known DNA damage and repair pathways. High-resolution real-time pathway activation data and protein expression profiles in conjunction with clustering analysis revealed that the five HALs induced various DNA damage and repair pathways. Among these, chloroacetaldehyde and trichloroacetaldehyde were found to be positively associated with genotoxicity, while dichloroacetaldehyde, bromoacetaldehyde, and tribromoacetaldehyde displayed negative associations. The protein effect level index, which are molecular end points derived from a toxicogenomics assay, exhibited a statistically significant positive correlation with the results of traditional genotoxicity assays, such as the comet assay (rp = 0.830 and p < 0.001) and SOS/umu assay (rp = 0.786 and p = 0.004). This yeast-based toxicogenomics assay, which employs a minimal set of gene biomarkers, can be used for mechanistic genotoxicity screening and assessment of HALs and other chemical compounds. These results contribute to bridging the knowledge gap regarding the molecular mechanisms underlying the genotoxicity of HALs and enable the categorization of HALs based on their distinct DNA damage and repair mechanisms.


Assuntos
Desinfetantes , Poluentes Químicos da Água , Purificação da Água , Desinfecção/métodos , Saccharomyces cerevisiae/genética , Toxicogenética/métodos , Purificação da Água/métodos , Dano ao DNA , Poluentes Químicos da Água/análise , Desinfetantes/análise , Desinfetantes/química
4.
Curr Opin Obstet Gynecol ; 35(4): 306-310, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37266567

RESUMO

PURPOSE OF REVIEW: The 2022 Supreme Court ruling in Dobbs vs Jackson marks a frightening new reality in America. Physicians and patients have been left confused and concerned regarding the broader implications of this ruling. Now that the constitutional right to an abortion has been overturned and the power has been relinquished to individual states, there is justifiable concern regarding the impact on in-vitro fertilization (IVF). This review explores the ways IVF and fertility care are at risk in the context of our new reality. RECENT FINDINGS: The decision to overturn the right to an abortion without specifying a viability standard opens the door to interpretation of when 'life' begins. Laws that do not specifically exempt IVF, or that include language suggesting that 'life begins at fertilization' pose a real threat to IVF. The potential for personhood laws poses a threat to embryo freezing and disposition, preimplantation genetic testing and culpability among other concerns. SUMMARY: Limitations to IVF may become an unintended consequence to the Dobbs decision, making IVF less efficient, more costly and unsafe, and inevitably limiting access to care. It is therefore crucial that public health legislation be rooted in science and not dictated by religion or politics. Physicians must act alongside legislators to protect reproductive freedom and access to care.


Assuntos
Aborto Induzido , Fertilidade , Feminino , Humanos , Gravidez , Fertilização , Estados Unidos , Cuidado Pré-Concepcional
5.
Trop Anim Health Prod ; 55(2): 72, 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36757509

RESUMO

Improved management of livestock in resource-limited settings can provide a means towards improved human nutrition and livelihoods. However, gastrointestinal nematodes (GIN) are a significant production-limiting factor. Anthelmintics play a role in GIN management; however, few anthelmintic classes are available in many low-middle-income countries. Utilising a limited range of classes may increase selection for anthelmintic resistance; therefore, strategies to reduce other selective pressures are of heightened importance. Avoiding anthelmintic underdosing is one such strategy, but it can be challenging without access to accurate bodyweight measurement. Many previous studies have used thoracic girth as a practical proxy for bodyweight in goats; however, they have rarely considered the potential impact of natural variation on therapeutic doses. Here, the relationship between bodyweight and thoracic girth was modelled using data from 820 goats from three Malawian biomes in two seasons, with the specific aim of avoiding underestimation of bodyweight. The internally cross-validated linear regression (∛Weight ~ 0.053 + 0.040*Girth, R2 = 0.92, rounded up to the nearest 5 kg) was validated against data from an additional 352 Malawian goats (1.4% of goats allocated an underdose and 10.2% allocated a dose > 200% of bodyweight). The equation was further externally validated using an historical dataset of 150 goats from Assam, India (2.7% of goats were allocated to an underdose and 24.8% allocated to a > 200% of bodyweight). These results suggest that a more globally generalisable approach may be feasible, provided the accuracy of the estimate is considered alongside the therapeutic index of the pharmaceutical.


Assuntos
Anti-Helmínticos , Doenças das Cabras , Nematoides , Infecções por Nematoides , Animais , Humanos , Infecções por Nematoides/veterinária , Cabras , Doenças das Cabras/tratamento farmacológico , Resistência a Medicamentos , Contagem de Ovos de Parasitas/veterinária , Anti-Helmínticos/farmacologia
6.
Ann Oncol ; 33(8): 836-844, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35715285

RESUMO

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.


Assuntos
COVID-19 , Neoplasias , COVID-19/epidemiologia , Humanos , Oncologia , Neoplasias/epidemiologia , Neoplasias/terapia , Pandemias , Estudos Prospectivos
7.
Surgeon ; 20(6): e382-e391, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35033455

RESUMO

BACKGROUND: To review whether online decision aids are available for patients contemplating pelvic exenteration (PE) for locally advanced and recurrent rectal cancer (LARC and LRRC). METHODS: A grey literature review was carried out using the Google Search™ engine undertaken using a predefined search strategy (PROSPERO database CRD42019122933). Written health information was assessed using the DISCERN criteria and International Patient Decision Aids Standards (IPDAS) with readability content assessed using the Flesch-Kincaid reading ease test and Flesch-Kincaid grade level score. RESULTS: Google search yielded 27, 782, 200 results for the predefined search criteria. 131 sources were screened resulting in the analysis of 6 sources. No sources were identified as a decision aid according to the IPDAS criteria. All sources provided an acceptable quality of written health information, scoring a global score of 3 for the DISCERN written assessment. The median Flesch-Kincaid reading ease was 50.85 (32.5-80.8) equating to a reading age of 15-18 years and the median Flesch-Kincaid grade level score was 7.65 (range 3-9.7), which equates to a reading age of 13-14. CONCLUSIONS: This study has found that there is a paucity of online information for patients contemplating PE. Sources that are available are aimed at a high health literate patient. Given the considerable morbidity associated with PE surgery there is a need for high quality relevant information in this area. A PDA should be developed to improve decision making and ultimately improve patient experience.


Assuntos
Compreensão , Neoplasias Retais , Humanos , Adolescente , Leitura , Internet , Tomada de Decisões , Neoplasias Retais/cirurgia
8.
Sensors (Basel) ; 22(18)2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36146393

RESUMO

The adverse health effects of the presence of lead in wastewater streams are well documented, with conventional methods of lead recovery and removal suffering from disadvantages such as high energy costs, the production of toxic sludge, and low lead selectivity. Klebsiella pneumoniae and Paraclostridium bifermentans have been identified as potential lead-precipitating species for use in a lead recovery bioreactor. Electrical impedance spectroscopy (EIS) on a low-cost device is used to determine the potential for the probe-free and label-free monitoring of cell growth in a bioreactor containing these bacteria. A complex polynomial is fit for several reactive equivalent circuit components. A direct correlation is found between the extracted supercapacitance and the plated colony-forming unit count during the exponential growth phase, and a qualitative correlation is found between all elements of the measured reactance outside the exponential growth phase. Strong evidence is found that Pb(II) ions act as an anaerobic respiration co-substrate for both cells observed, with changes in plated count qualitatively mirrored in the Pb(II) concentration. Guidance is given on the implementation of EIS devices for continuous impedance monitoring.


Assuntos
Esgotos , Águas Residuárias , Bactérias , Espectroscopia Dielétrica/métodos , Impedância Elétrica , Chumbo , Esgotos/microbiologia
9.
Int J Mol Sci ; 23(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36293112

RESUMO

The study focused on determining the microbial precipitation abilities of bacterial strains that were isolated from an industrially obtained Pb(II)-resistant microbial consortium. Previous research has demonstrated the effectiveness of the consortium on the bioprecipitation and adsorption of Pb(II) from solution. The bioremediation of Pb(II) using microbial precipitation provides an alternative option for Pb(II) removal from wastewater. Both strains, Klebsiella pneumoniae and Paraclostridium bifermentans, were successfully isolated from the consortium obtained from a battery recycling plant in South Africa. The experiments were conducted over both 30 h and 5 d, providing insight into the short- and long-term precipitation abilities of the bacteria. Various initial concentrations of Pb(II) were investigated, and it was found that P. bifermentans was able to remove 83.8% of Pb(II) from solution with an initial Pb(II) concentration of 80 mg L-1, while K. pneumoniae was able to remove 100% of Pb(II) with the same initial Pb(II) concentration after approximately 5 d. With the same initial Pb(II) concentration, P. bifermentans was able to remove 86.1% of Pb(II) from solution, and K. pneumoniae was able to remove 91.1% of Pb(II) from solution after 30 h. The identities of the precipitates obtained for each strain vary, with PbS and Pb0 being the main species precipitated by P. bifermentans and PbO with either PbCl or Pb3(PO4)2 precipitated by K. pneumoniae. Various factors were investigated in each experiment, such as metabolic activity, nitrate concentration, residual Pb(II) concentration, extracellular and intracellular Pb(II) concentration and the precipitate identity. These factors provide a greater understanding of the mechanisms utilised by the bacteria in the bioprecipitation and adsorption of Pb(II). These results can be used as a step towards applying the process on an industrial scale.


Assuntos
Klebsiella pneumoniae , Águas Residuárias , Consórcios Microbianos , Nitratos/metabolismo , Biodegradação Ambiental , Bactérias/metabolismo , Adsorção
10.
Molecules ; 27(21)2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36364207

RESUMO

Electrokinetic remediation has, in recent years, shown great potential in remediating polluted environments. The technology can efficiently remove heavy metals, chlorophenols, polychlorinated biphenyls, phenols, trichloroethane, benzene, toluene, ethylbenzene, and xylene (BTEX) compounds and entire petroleum hydrocarbons. Electrokinetic remediation makes use of electrolysis, electroosmosis, electrophoresis, diffusion, and electromigration as the five fundamental processes in achieving decontamination of polluted environments. These five processes depend on pH swings, voltage, electrodes, and electrolytes used in the electrochemical system. To apply this technology at the field scale, it is necessary to pursue the design of effective processes with low environmental impact to meet global sustainability standards. It is, therefore, imperative to understand the roles of the fundamental processes and their interactions in achieving effective and sustainable electrokinetic remediation in order to identify cleaner alternative solutions. This paper presents an overview of different processes involved in electrokinetic remediation with a focus on the effect of pH, electrodes, surfactants, and electrolytes that are applied in the remediation of contaminated soil and how these can be combined with cleaner technologies or alternative additives to achieve sustainable electrokinetic remediation. The electrokinetic phenomenon is described, followed by an evaluation of the impact of pH, surfactants, voltage, electrodes, and electrolytes in achieving effective and sustainable remediation.


Assuntos
Recuperação e Remediação Ambiental , Poluentes do Solo , Poluentes do Solo/análise , Solo/química , Tensoativos/análise , Eletrodos , Eletrólitos , Concentração de Íons de Hidrogênio
11.
Environ Monit Assess ; 194(11): 831, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36163406

RESUMO

High frequency ultraviolet - visible (UV-VIS) sensors offer a way of improving dissolved organic carbon (DOC) load estimates in rivers as they can be calibrated to DOC concentration. This is an improvement on periodic grab sampling, or the use of pumped sampling systems which store samples in-field before collection. We hypothesised that the move to high frequency measurements would increase the load estimate based on grab sampling due to systemic under-sampling of high flows. To test our hypotheses, we calibrated two sensors in contrasting catchments (Exe and Bow Brook, UK) against weekly grab sampled DOC measurements and then created an hourly time series of DOC for the two sites. Taking this measurement as a 'true' value of DOC load, we simulated 1,000 grab sampling campaigns at weekly, fortnightly and monthly frequency to understand the likely distribution of load and error estimates. We also performed an analysis of daily grab samples collected using a pumped storage sampling system with weekly collection. Our results show that: a) grab sampling systemically underestimates DOC loads and gives positively skewed distributions of results, b) this under-estimation and positive skew decreases with increasing sampling frequency, c) commonly used estimates of error in the load value are also systemically lowered by the oversampling of low, stable flows due to their dependence on the variance in the flow-weighted mean concentration, and d) that pumped storage systems may lead to under-estimation of DOC and over estimation of specific ultra-violet absorbance (SUVA), a proxy for aromaticity, due to biodegradation during storage.


Assuntos
Matéria Orgânica Dissolvida , Monitoramento Ambiental , Carbono/análise , Monitoramento Ambiental/métodos , Rios
12.
Molecules ; 26(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209142

RESUMO

The objective of the study was to gather insight into the metabolism of lead-removing microorganisms, coupled with Pb(II) removal, biomass viability and nitrate concentrations for Pb(II) bioremoval using an industrially obtained microbial consortium. The consortium used for study has proven to be highly effective at removing aqueous Pb(II) from solution. Anaerobic batch experiments were conducted with Luria-Bertani broth as rich growth medium over a period of 33 h, comparing a lower concentration of Pb(II) with a higher concentration at two different nutrient concentrations. Metabolite profiling and quantification were conducted with the aid of both liquid chromatography coupled with tandem mass spectroscopy (UPLC-HDMS) in a "non-targeted" fashion and high-performance liquid chromatography (HPLC) in a "targeted" fashion. Four main compounds were identified, and a metabolic study was conducted on each to establish their possible significance for Pb(II) bioremoval. The study investigates the first metabolic profile to date for Pb(II) bioremoval, which in turn can result in a clarified understanding for development on an industrial and microbial level.


Assuntos
Biomassa , Chumbo/metabolismo , Metaboloma , Consórcios Microbianos , Águas Residuárias/microbiologia , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental
13.
J Sport Exerc Psychol ; 43(3): 248-258, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33952704

RESUMO

The authors explored how sport structure predisposed a team to subgroup formation and influenced athlete interactions and team functioning. A season-long qualitative case study was undertaken with a nationally ranked Canadian track and field team. Semistructured interviews were conducted with coaches (n = 4) and athletes (n = 11) from different event groups (e.g., sprinters, jumpers) at the beginning and at the end of the season. The results highlighted constraints that directly impacted athlete interactions and predisposed the group to subgroup formation (e.g., sport/event type, facility/schedule limitations, team size/change over time). The constraints led to structural divides that impacted interactions but could be overcome through team building, engaging with leaders, and prioritizing communication. These findings underline how structure imposed by the design of sports impacts teammate interactions and how practitioners, coaches, and athletes can manage groups when facing such constraints. The authors describe theoretical and practical implications while also proposing potential future directions.


Assuntos
Esportes , Atletas , Canadá , Humanos , Estações do Ano
14.
Soc Sci Res ; 94: 102446, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33648680

RESUMO

In formulating views of just reward for high-status and low-status work, do ordinary citizens take cues from their nation's public stance on income inequality as institutionally embedded in their welfare state, i.e. their social welfare and labor market policies, their "welfarism"? How large a morally correct earnings gap flows from that? Our multilevel analyses (fixed effects, random intercepts) replicate prior research on the impact of individual characteristics and socioeconomic development. They open new territory with the discovery that public opinion on legitimate/just earnings of high-status occupations aligns moderately strongly with welfarism, ceteris paribus, with welfare state citizens advocating lower pay for the elite but not higher pay for working-class occupations: The welfare state is not (or no longer) a matter of helping the poor but instead of bringing down the elite, "cutting down the tall poppies". Data: World Inequality Study v2.1: 30 countries, 71 surveys, and over 88,000 individuals.


Assuntos
Renda , Ocupações , Humanos , Seguridade Social , Fatores Socioeconômicos
15.
J Relig Health ; 60(3): 1924-1936, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33415602

RESUMO

Perinatal autopsy rates have declined significantly in recent decades. There is a lack of consensus concerning the potential religious influences for bereaved parents in their decision making process for post-mortem. This online study of British and Irish maternity healthcare chaplains explored their understanding of general and local perinatal post-mortem procedures and their experiences in the support of parents. Participants included Christian, Muslim and non-faith chaplains. No chaplain identified any religious prohibition to perinatal post-mortem. A majority of chaplains reported that they had been asked about post-mortem by parents; only a minority felt adequately prepared. A key recommendation is that following appropriate training chaplains may be well placed to support colleagues and parents during the decision making process.


Assuntos
Luto , Clero , Autopsia , Atenção à Saúde , Feminino , Humanos , Irlanda , Gravidez , Natimorto , Reino Unido
16.
J Intern Med ; 288(5): 581-592, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32638487

RESUMO

BACKGROUND: Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. METHODS: A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. RESULTS: A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min-1 /1.73 m2 were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. CONCLUSION: In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.


Assuntos
Biomarcadores/sangue , Infarto do Miocárdio/complicações , Proteômica , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Adrenomedulina/sangue , Idoso , Feminino , Fator 15 de Diferenciação de Crescimento/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Perilipina-2/sangue , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/sangue , Receptores do Fator de Necrose Tumoral/sangue
17.
Blood ; 132(17): 1770-1780, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-30206115

RESUMO

Hemoglobinopathies are caused by genetic mutations that result in abnormal hemoglobin molecules, resulting in hemolytic anemia. Chronic complications involving the lung parenchyma, vasculature, and cardiac function in hemoglobinopathies result in impaired gas exchange, resulting in tissue hypoxia. Hypoxia is defined as the deficiency in the amount of oxygen reaching the tissues of the body and is prevalent in patients with hemoglobinopathies, and its cause is often multifactorial. Chronic hypoxia in hemoglobinopathies is often a sign of disease severity and is associated with increased morbidity and mortality. Therefore, a thorough understanding of the pathophysiology of hypoxia in these disease processes is important in order to appropriately treat the underlying cause and prevent complications. In this article, we discuss management of hypoxia based on three different cases: sickle cell disease, ß-thalassemia, and hereditary spherocytosis. These cases are used to review the current understanding of the disease pathophysiology, demonstrate the importance of a thorough clinical history and physical examination, explore diagnostic pathways, and review the current management.


Assuntos
Anemia Falciforme/complicações , Hipóxia/etiologia , Hipóxia/terapia , Esferocitose Hereditária/complicações , Talassemia beta/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Br J Surg ; 107(12): 1667-1672, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32618371

RESUMO

BACKGROUND: Patients undergoing surgery for soft tissue sarcoma have high morbidity rates, particularly after preoperative radiation therapy (RT). An enhanced recovery after surgery (ERAS) programme may improve perioperative outcomes in abdominal surgery. This study reported outcomes of an ERAS programme tailored to patients with soft tissue sarcoma. METHODS: A prospective ERAS protocol was implemented in 2015 at a high-volume sarcoma centre. Patients treated within the ERAS programme from 2015 to 2018 were case-matched retrospectively with patients treated between 2012 and 2018 without use of the protocol, matched by surgical site, surgeon, sarcoma histology and preoperative RT treatment. Postoperative outcomes, specifically wound complications and duration of hospital stay, were reported. RESULTS: In total, 234 patients treated within the ERAS programme were matched with 237 who were not. The ERAS group had lower wound dehiscence rates overall (2 of 234 (0·9 per cent) versus 31 of 237 (13·1 per cent); P < 0·001), after preoperative RT (0 of 41 versus 11 of 51; P = 0·004) and after extremity sarcoma surgery (0 of 54 versus 6 of 56; P = 0·040) compared with the non-ERAS group. Rates of postoperative ileus or obstruction were lower in the ERAS group (21 of 234 (9·9 per cent) versus 40 of 237 (16·9 per cent); P = 0·016) and in those with retroperitoneal sarcoma (4 of 36 versus 15 of 36; P = 0·007). Duration of hospital stay was shorter in the ERAS group (median 5 (range 0-36) versus 6 (0-67) days; P = 0·003). CONCLUSION: Treatment within an ERAS protocol for patients with soft tissue sarcoma was associated with lower morbidity and shorter hospital stay.


ANTECEDENTES: Los pacientes sometidos a cirugía por sarcoma de tejido blando (soft tissue sarcoma, STS) tienen altas tasas de morbilidad, particularmente después de la radioterapia preoperatoria (RT). El programa de recuperación intensificada después de la cirugía (enhanced recovery after surgery, ERAS) puede mejorar los resultados perioperatorios en la cirugía abdominal. Este estudio analizó los resultados de un programa ERAS diseñado para pacientes con STS. MÉTODOS: Se implementó un protocolo prospectivo ERAS en el año 2015 en un centro de alto volumen de sarcomas. Los pacientes en ERAS desde 2015 hasta 2018 fueron emparejados retrospectivamente con pacientes sin ERAS desde 2012 hasta 2018, según la localización quirúrgica, el cirujano, la histología del sarcoma y el tratamiento con RT preoperatoria. Se analizaron los resultados postoperatorios, específicamente las complicaciones de la herida y la duración de la estancia hospitalaria (length of stay, LOS). RESULTADOS: En total, 234 pacientes tratados con ERAS se compararon con 237 pacientes no tratados con ERAS. Los pacientes con ERAS tuvieron tasas globales más bajas de dehiscencia de la herida (2 (0,9%) versus 31 (13,1%), P < 0,001)), después de la RT preoperatoria (0 versus 11 (21,6%), P = 0,004)), y después de la cirugía de STS de extremidades (0 versus 6 (0,7%), P = 0,04)) en comparación con los pacientes no ERAS. Las tasas de íleo u obstrucción postoperatorias fueron más bajas en el grupo ERAS (21 (9,9%) versus 40 (16,9%), P = 0,02)) y en aquellos pacientes con sarcoma retroperitoneal (4 (11,1%) versus 15 (41,7%), P = 0,007)). La mediana (rango) de la LOS fue más corta en los pacientes con ERAS que fue de 5 (0-36) días que en los pacientes sin ERAS que fue de 6 (0-67) días (P = 0,003). CONCLUSIÓN: ERAS para pacientes con STS se asoció con una menor morbilidad y una estancia hospitalaria más corta.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Sarcoma/cirurgia , Procedimentos Clínicos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
19.
Phys Rev Lett ; 124(17): 171102, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32412252

RESUMO

The first detection of gravitational waves by the Laser Interferometer Gravitational-Wave Observatory (LIGO) in 2015 launched the era of gravitational-wave astronomy. The quest for gravitational-wave signals from objects that are fainter or farther away impels technological advances to realize ever more sensitive detectors. Since 2019, one advanced technique, the injection of squeezed states of light, is being used to improve the shot-noise limit to the sensitivity of the Advanced LIGO detectors, at frequencies above ∼50 Hz. Below this frequency, quantum backaction, in the form of radiation pressure induced motion of the mirrors, degrades the sensitivity. To simultaneously reduce shot noise at high frequencies and quantum radiation pressure noise at low frequencies requires a quantum noise filter cavity with low optical losses to rotate the squeezed quadrature as a function of frequency. We report on the observation of frequency-dependent squeezed quadrature rotation with rotation frequency of 30 Hz, using a 16-m-long filter cavity. A novel control scheme is developed for this frequency-dependent squeezed vacuum source, and the results presented here demonstrate that a low-loss filter cavity can achieve the squeezed quadrature rotation necessary for the next planned upgrade to Advanced LIGO, known as "A+."

20.
Alcohol Clin Exp Res ; 44(2): 541-552, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31943243

RESUMO

BACKGROUND: Students' alcohol use behaviors are shaped by the attitudes and behaviors of others, especially the peers within students' proximal social groups. Explaining the association between perceived drinking norms and alcohol use, researchers propose contradicting pathways that focus on conformity (i.e., social norms predict alcohol use) and projection (i.e., alcohol use predicts perceived norms). The current study examined the extent to which conformity and projection processes were evident in the association between college student alcohol use and the perceived alcohol use norms for students' club sport teams. METHODS: The sample comprised 1,054 college students (61% female) nested in 35 intact same-sex club sport teams. On 3 separate occasions during a single school year (3-month lag), participants reported drinking frequency and perceptions of descriptive and injunctive group drinking norms. We employed random intercepts cross-lagged panel modeling to estimate prospective within-person associations separately from stable trait-like between-person associations. RESULTS: Descriptive and injunctive group drinking norms were both positively related to students' alcohol use frequency at the between-person level. Individuals nevertheless demonstrated variability at the within-person level. Results revealed a strong contemporaneous association between descriptive norms and alcohol use frequency within each timepoint, but no prospective associations. Models including perceptions of injunctive drinking norms demonstrated similar contemporaneous associations with alcohol use frequency, but also identified significant prospective associations signifying conformity. CONCLUSIONS: Findings align with previous research reporting a strong and positive association between student's self-reported alcohol use and subjective peer alcohol use norms. After disentangling within- and between-person effects to probe for conformity and projection processes, the current findings are somewhat contrary to previous research that has reported reciprocal relationships between social norms and alcohol use behavior. Further investigation of the potential conformity and projection mechanisms of social norms is critical to advance norm-based strategies to reduce harm.


Assuntos
Consumo de Álcool na Faculdade/psicologia , Grupo Associado , Esportes/psicologia , Esportes/tendências , Estudantes/psicologia , Universidades/tendências , Adolescente , Atletas/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Percepção , Estudos Prospectivos , Adulto Jovem
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