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PURPOSE OF REVIEW: Higher degrees of myopia are currently being treated with refractive surgery. However, there is limited characterization and outcomes data for this cohort. This article aims to review the literature on highly myopic patients who had refractive surgery and present a retrospective analysis of 149 patients (270 eyes) with high to extreme myopia (≤-5.0D SE) who underwent refractive surgery [laser-assisted subepithelial keratomileusis (LASIK), photorefractive keratectomy (PRK), or implantable collamer lense (ICL)] at a single practice. RECENT FINDINGS: There is substantial literature on the efficacy of LASIK, PRK, and phakic intraocular lenses for refractive error correction, but a dearth of studies on patients with high to extreme myopia undergoing different types of refractive surgery. Our study reveals that this cohort of patients has excellent outcomes with minimal complications. SUMMARY: Our study reveals that the average preoperative myopia was highest in ICL patients (-10.03D), followed by PRK (-7.21D), and LASIK (-7.04D) patients. Not surprisingly, eyes with high myopia and thin corneas were offered and elected ICLs for their procedure. Highly myopic patients achieved outcomes consistent with data reported in the literature- average postoperative uncorrected visual acuity was 20/20 for LASIK and ICL eyes and 20/25 for PRK eyes.
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Ceratectomia Fotorrefrativa , Acuidade Visual , Humanos , Acuidade Visual/fisiologia , Resultado do Tratamento , Ceratectomia Fotorrefrativa/métodos , Implante de Lente Intraocular/métodos , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Refração Ocular/fisiologia , Estudos Retrospectivos , Miopia Degenerativa/cirurgia , Miopia Degenerativa/fisiopatologia , Miopia/cirurgia , Miopia/fisiopatologia , Lentes Intraoculares Fácicas , Adulto , Masculino , FemininoRESUMO
A handball is one of two technical skills used to dispose of the ball in Australian Football. Previous research has only considered handball effectiveness in the analysis of team performance and there is a need to understand whether there are other more important characteristics of handball execution that explain effectiveness (i.e., performance). 1342 handballs from Australian Football League matches were analysed. Ten characteristic variables were created that represent the context and execution of each handball included in the analysis. A mixed effects generalised linear model was used to evaluate the effect of the (ten) characteristics on handball outcome. Three out of ten characteristics were associated with handball outcome, and these related to the posture of the handballer and the type of defensive pressure applied to the handballer and the receiver of the handball. These findings explain both how to increase handball effectiveness and how to reduce the handball effectiveness of an opposition team. Given the important role of handballing in passing sequences and maintaining ball possession, the practical application of these findings could enhance overall team performance.
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Desempenho Atlético , Humanos , Austrália , Modelos Lineares , Esportes de EquipeRESUMO
OBJECTIVE: We aimed to compare discharge opioid prescriptions pre- and post-ERAS implementation. SUMMARY OF BACKGROUND DATA: ERAS programs decrease inpatient opioid use, but their relationship with postdischarge opioids remains unclear. METHODS: All patients undergoing hysterectomy between October 2016 and November 2020 and pancreatectomy or hepatectomy between April 2017 and November 2020 at 1 tertiary care center were included. For each procedure, ERAS was implemented during the study period. PSM was performed to compare pre - versus post-ERAS patients on discharge opioids (number of pills and oral morphine equivalents). Patients were matched on age, sex, race, payor, American Society of Anesthesiologists score, prior opioid use, and procedure. Sensitivity analyses in open versus minimally invasive surgery cohorts were performed. RESULTS: A total of 3983 patients were included (1929 pre-ERAS; 2054 post-ERAS). Post-ERAS patients were younger (56.0 vs 58.4 years; P < 0.001), more often female (95.8% vs 78.1%; P < 0.001), less often white (77.2% vs 82.0%; P < 0.001), less often had prior opioid use (20.1% vs 28.1%; P < 0.001), and more often underwent hysterectomy (91.1% vs 55.7%; P < 0.001). After PSM, there were no significant differences between cohorts in baseline characteristics. Matched post-ERAS patients were prescribed fewer opioid pills (17.4 pills vs 22.0 pills; P < 0.001) and lower oral morphine equivalents (129.4 mg vs 167.6 mg; P < 0.001) than pre-ERAS patients. Sensitivity analyses confirmed these findings [open (18.8 pills vs 25.4 pills; P < 0.001 \ 138.9 mg vs 198.7 mg; P < 0.001); minimally invasive surgery (17.2 pills vs 21.1 pills; P < 0.001 \ 127.1 mg vs 160.1 mg; P < 0.001). CONCLUSIONS: Post-ERAS patients were prescribed significantly fewer opioids at discharge compared to matched pre-ERAS patients.
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Recuperação Pós-Cirúrgica Melhorada , Transtornos Relacionados ao Uso de Opioides , Humanos , Feminino , Analgésicos Opioides/uso terapêutico , Alta do Paciente , Assistência ao Convalescente , Dor Pós-Operatória/tratamento farmacológico , Derivados da MorfinaRESUMO
Recently, we introduced an optimized and automated Multi-Attribute Method (MAM) workflow, which (a) significantly reduces the number of missed cleavages using an automated two-step digestion procedure and (b) dramatically reduces chromatographic peak tailing and carryover of hydrophobic peptides by implementing less retentive reversed-phase column chemistries. Here, further insights are provided on the impact of postdigest acidification and the importance of maintaining hydrophobic peptides in solution using strong chaotropic agents after digestion. We demonstrate how oxidation can significantly increase the solubility of hydrophobic peptides, a fact that can have a profound impact on quantitation of oxidation levels if care is not taken in MAM workflows. We conclude that (a) postdigestion acidification can result in significant acid-catalyzed deamidation during storage in an autosampler at 5 °C and (b) a strong chaotropic agent, such as guanidine hydrochloride, is critical for preventing loss of hydrophobic peptides through adsorption, which can result in (sometimes extreme) biases in quantitation of tryptophan oxidation levels. An optimized method is presented, which effectively addressed acid-catalyzed deamidation and solubility of hydrophobic peptides in MAM workflows.
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Peptídeos , Fluxo de Trabalho , Solubilidade , Peptídeos/química , CatáliseRESUMO
PURPOSE OF REVIEW: The purpose of this article is to provide a review of the literature on refractive lens exchange and present a retrospective analysis of 55 patients who underwent refractive lens exchange at a single practice. RECENT FINDINGS: Our study substantiates refractive lens exchange as an important option for presbyopic patients, hyperopic patients or patients with extremely high refractive error who desire spectacle independence. SUMMARY: Our study reveals that the refractive lens exchange population is younger than the average cataract population and their primary motivations are to resolve hyperopic or myopic refractive errors, gain spectacle independence, and address near vision loss. A variety of presbyopia-addressing intraocular lens options are available and we present our experience with multifocal, extended depth-of-focus, light-adjustable, and monofocal lenses.
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Cristalino , Lentes Intraoculares , Presbiopia , Humanos , Acuidade Visual , Estudos Retrospectivos , Implante de Lente Intraocular , Presbiopia/cirurgiaRESUMO
Transgender and gender-diverse (TGD) people endure numerous physical and mental health disparities secondary to lifelong stigma and marginalization, which are often perpetuated in medical spaces. Despite such barriers, TGD people are seeking gender-affirming care (GAC) with increased frequency. GAC facilitates the transition from the sex assigned at birth to the affirmed gender identity and is comprised of hormone therapy (HT) and gender-affirming surgery (GAS). The anesthesia professional is uniquely poised to serve as an integral support for TGD patients within the perioperative space. To provide affirmative perioperative care to TGD patients, anesthesia professionals should understand and attend to the biological, psychological, and social dimensions of health that are relevant to this population. This review outlines the biological factors that impact the perioperative care of TGD patients, such as the management of estrogen and testosterone HT, safe use of sugammadex, interpretation of laboratory values in the context of HT, pregnancy testing, drug dosing, breast binding, altered airway and urethral anatomy after prior GAS, pain management, and other GAS considerations. Psychosocial factors are reviewed, including mental health disparities, health care provider mistrust, effective patient communication, and the interplay of these factors in the postanesthesia care unit. Finally, recommendations to improve TGD perioperative care are reviewed through an organizational approach with an emphasis on TGD-focused medical education. These factors are discussed through the lens of patient affirmation and advocacy with the intent to educate the anesthesia professional on the perioperative management of TGD patients.
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Cirurgia de Readequação Sexual , Pessoas Transgênero , Transexualidade , Recém-Nascido , Humanos , Masculino , Feminino , Pessoas Transgênero/psicologia , Identidade de Gênero , TestosteronaRESUMO
This study aimed to determine whether machine learning models based on technical performance and not score margin could be used to predict end-of-match outcome of Australian football matches in real-time. If efficacious, these models could be used to generate insights about team performance and support the decision-making of coaches during matches. A database of 168 team technical performance indicators from 829 Australian Football League matches played between 2017 and 2021 was used. Two feature sets (data-driven and data-informed) were used to train and evaluate six models (generalised linear model, random forest and adaboost) on match outcome prediction (Win/Loss) over 120 epochs (a representation of normalised time during each match). All models performed well (mean classification accuracy = 73.5-75.8%) in comparison with a benchmark score-based model (mean classification accuracy = 77.4%). Data-informed feature sets performed better than data-driven in most cases. Classification accuracy was low at the start of a match (45.7-48.8%) but increased to a peak near the end of a match (87.2-92.7%). These findings suggest that any of the employed models can be used to formulate in-match decision support. The model which is best in practice will depend on factors such as time-cost trade-off, feasibility and the perceived value of its suggestions.
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Desempenho Atlético , Humanos , Austrália , Comportamento Competitivo , Esportes de EquipeRESUMO
Peptide mapping by liquid chromatography mass spectrometry (LC-MS) and the related multi-attribute method (MAM) are well-established analytical tools for verification of the primary structure and mapping/quantitation of co- and post-translational modifications (PTMs) or product quality attributes in biopharmaceutical development. Proteolytic digestion is a key step in peptide mapping workflows, which traditionally is labor-intensive, involving multiple manual steps. Recently, simple high-temperature workflows with automatic digestion were introduced, which facilitate robustness and reproducibility across laboratories. Here, a modified workflow with an automatic digestion step is presented, which includes a two-step digestion at high and low temperatures, as opposed to the original one-step digestion at a high temperature. The new automatic digestion workflow significantly reduces the number of missed cleavages, obtaining a more complete digestion profile. In addition, we describe how chromatographic peak tailing and carry-over is dramatically reduced for hydrophobic peptides by switching from the traditional C18 reversed-phase (RP) column chemistry used for peptide mapping to a less retentive C4 column chemistry. No negative impact is observed on MS/MS-derived sequence coverage when switching to a C4 column chemistry. Overall, the new peptide mapping workflow significantly reduces the number of missed cleavages, yielding more robust and simple data interpretation, while providing dramatically reduced tailing and carry-over of hydrophobic peptides.
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Peptídeos , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Cromatografia Líquida/métodos , Mapeamento de Peptídeos/métodos , Peptídeos/química , Fluxo de TrabalhoRESUMO
The use of bismuth in the society has steadily increased during the last decades, both as a substitute for lead in hunting ammunition and various metallurgical applications, as well as in a range of consumer products. At the same time, the environmental behavior of bismuth is largely unknown. Here, the binding of bismuth(III) to organic soil material was investigated using extended X-ray absorption spectroscopy (EXAFS) and batch experiments. Moreover, the capacity of suwannee river fulvic acid (SRFA) to enhance the solubility of metallic bismuth was studied in a long-term (2 years) equilibration experiment. Bismuth(III) formed exceptionally strong complexes with the organic soil material, where >99% of the added bismuth(III) was bound by the solid phase, even at pH 1.2. EXAFS data suggest that bismuth(III) was bound to soil organic matter as a dimeric Bi3+ complex where one carboxylate bridges two Bi3+ ions, resulting in a unique structural stability. The strong binding to natural organic matter was verified for SRFA, dissolving 16.5 mmol Bi per gram carbon, which largely exceeds the carboxylic acid group density of this compound. Our study shows that bismuth(III) will most likely be associated with natural organic matter in soils, sediments, and waters.
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Bismuto , Solo , Bismuto/química , Rios/química , Solubilidade , Espectroscopia por Absorção de Raios XRESUMO
Youth violence remains a significant public health problem despite efforts to address it. We describe the evaluation results of Youth Empowerment Solutions (YES), an after-school active learning program implemented by trained local teachers and designed to engage middle school youth in multi-systematic promotive behaviors at the individual-, interpersonal-, and community-level to make lasting positive changes within the context of institutional disadvantages, such as racism. First, we used a modified randomized controlled trial design to examine the direct and indirect influence of YES on prosocial and delinquent behaviors 12 months after the conclusion of the program, through youth empowerment. Next, we evaluated these models by race, to determine if the intervention equitably promotes prosocial outcomes and decreases aggressive behaviors. Among 329 middle school students, YES participation enhanced prosocial behaviors through empowerment, and directly reduced aggressive behaviors a year after the conclusion of the program. This trend was particularly pronounced for African American youth. These effects were found after controlling for age, sex, and behavioral outcomes at baseline, and across different schools and teachers, suggesting that YES can also be sustainable and readily implemented by communities. The implications of the results for youth violence prevention, empowerment theory and intervention development and practice for ethnic minority youth who face structural disenfranchisement are discussed.
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Comportamento do Adolescente , Altruísmo , Adolescente , Agressão , Etnicidade , Humanos , Grupos Minoritários , Violência/prevenção & controleRESUMO
We investigated the impact of preoperative gabapentin on perioperative intravenous opioid requirements and post anesthesia care unit length of stay (PACU LOS) for patients undergoing laparoscopic and vaginal hysterectomies within an Enhanced Recovery After Surgery (ERAS) pathway. A multidisciplinary team retrospectively examined 2,015 patients who underwent laparoscopic or vaginal hysterectomies between October 2016 and January 2020 at a single academic institution. The average PACU LOS was 168 min among patients who did not receive gabapentin vs. 180 min both among patients who received ≤ 300 mg of gabapentin and patients who received > 300 mg of gabapentin. After adjusting for demographics and medical comorbidities, PACU LOS for patients given ≤ 300 mg gabapentin was 6% longer (rate ratio (RR) = 1.06, 95% CI = 1.01-1.11) than for patients who were not given gabapentin, and for patients who received > 300 mg of gabapentin was 7% longer (RR = 1.07, 95%CI = 1.01-1.13) than for those who did not receive gabapentin. Patients who received ≤ 300 mg gabapentin received 9% less perioperative intravenous hydromorphone than patients who did not receive gabapentin (RR = 0.91, 95% CI = 0.86 - 0.97); patients who received > 300 mg of gabapentin received 12% less perioperative intravenous hydromorphone than patients who did not receive gabapentin (RR = 0.88, 95% CI = 0.82 - 0.95). These findings represent an absolute difference of 0.09 mg intravenous hydromorphone. There were no statistically significant differences in total intravenous fentanyl received. Preoperative gabapentin given as part of an ERAS pathway is associated with statistically but not clinically significant increases in PACU LOS and decreases in total perioperative intravenous opioid use.
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Analgésicos Opioides , Recuperação Pós-Cirúrgica Melhorada , Analgésicos Opioides/uso terapêutico , Feminino , Gabapentina , Humanos , Hidromorfona , Histerectomia , Tempo de Internação , Dor Pós-Operatória/tratamento farmacológico , Estudos RetrospectivosRESUMO
In household-based surveys that include rapid HIV testing services (HTS), passive referral systems that give HIV-positive participants information about how and where to access ART but minimal follow-up support from survey staff may result in suboptimal linkage. In the 2017 Namibia Population-based HIV Impact Assessment (NAMPHIA), we piloted a system of active linkage to care and ART (ALCART) that utilized the infrastructure of existing community-based partner organizations (CBPOs). All HIV-positive participants age 15-64 years not on ART were given standard passive referrals to ART plus the option to participate in ALCART. Cases were assigned to CBPOs in participants' localities. Healthcare workers from the CBPO's contacted cases and facilitated their linkage to facility-based ART. A total of 510 participants were eligible and consented to ALCART. The majority were new diagnoses (80.8%), while the remainder were previously diagnosed but not on ART (19.2%). Of the 510, 473 (92.7%) were successfully linked into care. Of these, all but one initiated ART. Our ALCART system used existing CBPOs and contributed to >90% linkage-to-care and >99% ART-initiation among linked participants in a large, nationally-representative survey. This approach can be used to improve the potential benefits of HTS in other large population-based surveys.
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Infecções por HIV , Teste de HIV , Adolescente , Adulto , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Pessoa de Meia-Idade , Namíbia/epidemiologia , Encaminhamento e Consulta , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: The Massachusetts General Hospital is a large, quaternary care institution with 58 operating rooms, 164 anesthesiologists, 76 certified nurse anesthetists (CRNAs), an anesthesiology residency program that admits 25 residents annually, and 35 surgeons who perform laparoscopic, vaginal, and open hysterectomies. In March of 2018, our institution launched an Enhanced Recovery After Surgery (ERAS) pathway for patients undergoing hysterectomy. To implement the anesthesia bundle of this pathway, an intensive 14-month educational endeavor was created and put into effect. There were no subsequent additional educational interventions. METHODS: We retrospectively reviewed records of 2570 patients who underwent hysterectomy between October 2016 and March 2020 to determine adherence to the anesthesia bundle of the ERAS Hysterectomy pathway. RESULTS: Increased adherence to the four elements of the anesthesia bundle (p < 0.001) was achieved during the intervention period. Compliance with the pathway was sustained in the post-intervention period despite no additional actions. CONCLUSIONS: Implementing the anesthesia bundle of an ERAS pathway in a large anesthesia group with diverse providers successfully occurred using implementation science-based approach of intense interventions, and these results were maintained after the intervention ceased.
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Serviço Hospitalar de Anestesia , Anestesiologia/métodos , Recuperação Pós-Cirúrgica Melhorada , Histerectomia , Feminino , Humanos , Massachusetts , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-con- trolled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.
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Substância Própria/virologia , Infecções Oculares Virais/tratamento farmacológico , Glucocorticoides/uso terapêutico , Ceratite Herpética/tratamento farmacológico , Prednisolona/análogos & derivados , Administração Oftálmica , Adulto , Antivirais/uso terapêutico , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Prednisolona/uso terapêutico , Resultado do Tratamento , Trifluridina/uso terapêutico , Acuidade Visual/fisiologiaRESUMO
An improved quantitative and qualitative understanding of the interaction of per- and polyfluoroalkyl substances (PFASs) and short-range ordered Fe (hydr)oxides is crucial for environmental risk assessment in environments low in natural organic matter. Here, we present data on the pH-dependent sorption behavior of 12 PFASs onto ferrihydrite. The nature of the binding mechanisms was investigated by sulfur K-edge X-ray absorption near-edge structure (XANES) spectroscopy and by phosphate competition experiments. Sulfur K-edge XANES spectroscopy showed that the sulfur atom of the head group of the sulfonated PFASs retained an oxidation state of +V after adsorption. Furthermore, the XANES spectra did not indicate any involvement of inner-sphere surface complexes in the sorption process. Adsorption was inversely related to pH (p < 0.05) for all PFASs (i.e., C3-C5 and C7-C9 perfluorocarboxylates, C4, C6, and C8 perfluorosulfonates, perfluorooctane sulfonamide, and 6:2 and 8:2 fluorotelomer sulfonates). This was attributed to the pH-dependent charge of the ferrihydrite surface, as reflected in the decrease of surface ζ-potential with increasing pH. The importance of surface charge for PFAS adsorption was further corroborated by the observation that the adsorption of PFASs decreased upon phosphate adsorption in a way that was consistent with the decrease in ferrihydrite ζ-potential. The results show that ferrihydrite can be an important sorbent for PFASs with six or more perfluorinated carbons in acid environments (pH ≤ 5), particularly when phosphate and other competitors are present in relatively low concentrations.
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Fluorocarbonos , Adsorção , Alcanossulfonatos , Compostos FérricosRESUMO
BACKGROUND: The first Canadian outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was identified in 2004 in Calgary, Alberta. Using a novel model of MRSA population-based surveillance, sociodemographic risk associations, yearly geospatial dissemination and prevalence of CA-MRSA infections over an 11 year period was identified in an urban healthcare jurisdiction of Calgary. METHODS: Positive MRSA case records, patient demographics and laboratory data were obtained from a centralized Laboratory Information System of Calgary Laboratory Services in Calgary, Alberta, Canada between 2004 and 2014. Public census data was obtained from Statistics Canada, which was used to match with laboratory data and mapped using Geographic Information Systems. RESULTS: During the study period, 52.5% of positive MRSA infections in Calgary were CA-MRSA cases. The majority were CMRSA10 (USA300) clones (94.1%; n = 4255), while the remaining case (n = 266) were CMRSA7 (USA400) clones. Period prevalence of CMRSA10 increased from 3.6 cases/100000 population in 2004, to 41.3 cases/100000 population in 2014. Geospatial analysis demonstrated wide dissemination of CMRSA10 annually in the city. Those who are English speaking (RR = 0.05, p < 0.0001), identify as visible minority Chinese (RR = 0.09, p = 0.0023) or visible minority South Asian (RR = 0.25, p = 0.015), and have a high median household income (RR = 0.27, p < 0.0001) have a significantly decreased relative risk of CMRSA10 infections. CONCLUSIONS: CMRSA10 prevalence increased between 2004 and 2007, followed by a stabilization of cases by 2014. Certain sociodemographic factors were protective from CMRSA10 infections. The model of MRSA population-surveillance and geomap outbreak events can be used to track the epidemiology of MRSA in any jurisdiction.
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Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Vigilância da População , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Adulto , Alberta/epidemiologia , Feminino , Sistemas de Informação Geográfica , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Análise EspacialRESUMO
Basal cells are multipotent airway progenitors that generate distinct epithelial cell phenotypes crucial for homeostasis and repair of the conducting airways. Little is known about how these progenitor cells expand and transition to differentiation to form the pseudostratified airway epithelium in the developing and adult lung. Here, we show by genetic and pharmacological approaches that endogenous activation of Notch3 signaling selectively controls the pool of undifferentiated progenitors of upper airways available for differentiation. This mechanism depends on the availability of Jag1 and Jag2, and is key to generating a population of parabasal cells that later activates Notch1 and Notch2 for secretory-multiciliated cell fate selection. Disruption of this mechanism resulted in aberrant expansion of basal cells and altered pseudostratification. Analysis of human lungs showing similar abnormalities and decreased NOTCH3 expression in subjects with chronic obstructive pulmonary disease suggests an involvement of NOTCH3-dependent events in the pathogenesis of this condition.
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Proteínas de Ligação ao Cálcio/metabolismo , Diferenciação Celular/fisiologia , Células Epiteliais/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Pulmão/embriologia , Proteínas de Membrana/metabolismo , Receptores Notch/metabolismo , Mucosa Respiratória/embriologia , Transdução de Sinais/fisiologia , Animais , Western Blotting , Técnicas de Cultura de Células , Imunofluorescência , Humanos , Imuno-Histoquímica , Hibridização In Situ , Proteína Jagged-1 , Camundongos , Microscopia Confocal , Reação em Cadeia da Polimerase em Tempo Real , Receptor Notch3 , Mucosa Respiratória/citologia , Proteínas Serrate-Jagged , Especificidade da EspécieRESUMO
AIMS: Previous genetic association studies have shown that variation in the GATA4 gene encoding the GATA binding protein 4, a binding protein that binds to the ANA sequence GATA, increase susceptibility for alcohol use disorder (AUD). In this study, we aimed to replicate those findings in an independent sample and analyze their association with anxiety. METHODS: Overall, 1044 individuals with AUD [534 European American (EA), 510 African Americans (AA)] and 645 controls [413 EA, 232 AA] were genotyped using 34 markers. Genotype and allele frequencies were compared between cases and controls using chi-square analysis. Other phenotype data were analyzed for possible associations with GATA4 single-nucleotide polymorphisms (SNPs) in individuals with AUD. RESULTS: Rs6601604 was nominally significantly associated with AUD in EA, and 3 SNPs (rs6990313, rs11250159 and rs17153694) showed trend-level significance (P < 0.10) in AA. However, none of the SNPs were significant after correcting for multiple testing. Haplotype analysis of the 34 SNPs did not find a significant association between haplotype blocks and AUD diagnosis after correcting for multiple testing. From the phenotype analysis, anxiety was associated with GATA4 SNP rs10112596 among the AA group with AUD after a correction for multiple testing. CONCLUSIONS: Although previous studies have shown a relationship between variants of the GATA4 gene and a diagnosis of AUD, we did not replicate these findings in our sample. Additional studies of variation in this gene are needed to elucidate whether polymorphisms of the GATA4 gene are associated with AUD and other alcohol-related phenotypes. SHORT SUMMARY: GATA4 variants were not associated with AUD in either the European ancestry or African ancestry groups after correcting for multiple comparisons. Rs10112596 demonstrated a significant relationship with an anxiety measure among the African ancestry group with AUD.
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Alcoolismo/genética , Ansiedade/genética , Fator de Transcrição GATA4/genética , Predisposição Genética para Doença/genética , Negro ou Afro-Americano/genética , Alcoolismo/complicações , Ansiedade/complicações , Estudos de Casos e Controles , Frequência do Gene , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único/genética , População Branca/genéticaRESUMO
Accurate forecasting of dairy cow milk yield is useful to dairy farmers, both in relation to financial planning and for detection of deviating yield patterns, which can be an indicator of mastitis and other diseases. In this study we developed a dynamic linear model (DLM) designed to forecast milk yields of individual cows per milking, as they are milked in milking robots. The DLM implements a Wood's function to account for the expected total daily milk yield. It further implements a second-degree polynomial function to account for the effect of the time intervals between milkings on the proportion of the expected total daily milk yield. By combining these 2 functions in a dynamic framework, the DLM was able to continuously forecast the amount of milk to be produced in a given milking. Data from 169,774 milkings on 5 different farms in 2 different countries were used in this study. A separate farm-specific implementation of the DLM was made for each of the 5 farms. To determine which factors would influence the forecast accuracy, the standardized forecast errors of the DLM were described with a linear mixed effects model (lme). This lme included lactation stage (early, middle, or late), somatic cell count (SCC) level (nonelevated or elevated), and whether or not the proper farm-specific version of the DLM was used. The standardized forecast errors of the DLM were only affected by SCC level and interactions between SCC level and lactation stage. Therefore, we concluded that the implementation of Wood's function combined with a second-degree polynomial is useful for dynamic modeling of milk yield in milking robots, and that this model has potential to be used as part of a mastitis detection system.
Assuntos
Bovinos/fisiologia , Indústria de Laticínios/métodos , Modelos Lineares , Mastite Bovina/diagnóstico , Leite/metabolismo , Animais , Contagem de Células/veterinária , Indústria de Laticínios/instrumentação , Fazendas , Feminino , Lactação , RobóticaRESUMO
BACKGROUND: Multiresistant bacteria (MRB) is an increasing problem. Early identification of patients with MRB is mandatory to avoid transmission and to target the antibiotic treatment. The emergency department (ED) is a key player in the early identification of patients who are colonized with MRB. There is currently sparse knowledge of both prevalence and risk factors for colonization with MRSA, ESBL, VRE, CPE and CD in acutely admitted patients in Western European countries including Denmark. To develop evidence-based screening tools for identifying carriers of resistant bacteria among acutely admitted patients, systematic collection of information on risk factors and exposures is required. Since a geographical variation is suspected, it is desirable to include emergency departments across the country. The aim of this project is to provide a comprehensive overview of prevalence and risk factors for MRSA, ESBL, VRE, CPE and CD colonization in patients admitted to Danish ED's. The objectives are to describe the prevalence and demography of resistance, co-infections, to identify risk factors for carrier state and to develop and validate a screening tool for identification of carriers. METHODS: Multicenter descriptive and analytic cross-sectional survey from January-May 2018 of around 10.000 acutely admitted patients > 18 years in 8 EDs for carrier state and risk factors for antibiotic resistant bacteria. Information about the background and possible risk factors for carrier status together with swabs from the nose, throat and rectum is collected and analyzed for MRSA, ESBL, VRE, CPE and CD. The prevalence of the resistant bacteria are calculated at hospital level, regional level and national level and described with relation to residency, sex, age and risk factors. A screening model for identification of carrier stage of resistant bacteria is developed and validated. DISCUSSION: The study will provide the prevalence of colonized patients with resistant bacteria on arrival to the ED and variation in demographic patterns, and will develop a clinical tool to identify certain risk groups. This will enable the clinician to target antibiotic treatments and to reduce the in-hospital spreading of resistant bacteria. This knowledge is important for implementing and evaluating antimicrobial stewardships, screening and infection control strategies. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03352167 (registration date: 20. November 2017).