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Critical drug studies explore the discursive and material dimensions of sexualised drug use to overcome individualised and often pathologising notions such as risk, safety, responsibility and pleasure. This article uses an object-oriented approach-following the use and flow of social apps, syringes and antiretroviral therapy (ART)-to analyse gay and bisexual Taiwanese men's drug practices. Interview data from fourteen men are used to articulate how objects were brought into gay and bisexual men's chemsex repertoire in ways that shaped individuals' safe-sex communication, intimacy maintenance and stigma negotiation. An object-oriented approach scrutinises risk, pleasure and identities in assemblages of the human and nonhuman, and can help identify new opportunities for implementing health promotion interventions and policies.
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Homosexualidad Masculina , Minorías Sexuales y de Género , Masculino , Humanos , Jeringas , Conducta Sexual , Parejas SexualesRESUMEN
BACKGROUND: To determine patient and surgical factors associated with the use of 360-degree laser retinopexy during primary pars plana vitrectomy (PPV) ± scleral buckle (SB) for rhegmatogenous retinal detachment (RRD) and its impact on surgical outcomes. METHODS: Patients who underwent PPV ± SB for repair of non-complex RRD at a single centre were included in this retrospective study. The primary outcome was single surgery anatomical success (SSAS). Secondary outcomes included visual acuity, epiretinal membrane formation, the presence of cystoid macular oedema, tonic pupil and corneal epithelial defects. Multiple logistic regression and multivariate regression was used. RESULTS: The study included 192 cases, of which 130 received 360-degree laser. Worse preoperative logMAR visual acuity (P = 0.009), male sex (P = 0.060), higher PVR grades, supplemental SB (P = 0.0468) and silicone oil/C3F8 tamponade (P < 0.0001) were associated with 360-degree laser use. No significant associations between 360-degree laser and SSAS (P = 0.079), final logMAR visual acuity (P = 0.0623), ERM development (P = 0.8208), postoperative CMO (P = 0.5946), tonic pupil (P > 0.9999) or corneal epithelial defects (P = N/A) were found. CONCLUSIONS: 360-degree laser retinopexy during primary PPV ± SB for RRD was associated with more complex cases and more extensive operations. Even when accounting for this, there was no difference in surgical outcomes or complication rates.
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One of the most challenging obstacles to realizing exascale computing is minimizing the energy consumption of L2 cache, main memory, and interconnects to that memory. For promising cryogenic computing schemes utilizing Josephson junction superconducting logic, this obstacle is exacerbated by the cryogenic system requirements that expose the technology's lack of high-density, high-speed and power-efficient memory. Here we demonstrate an array of cryogenic memory cells consisting of a non-volatile three-terminal magnetic tunnel junction element driven by the spin Hall effect, combined with a superconducting heater-cryotron bit-select element. The write energy of these memory elements is roughly 8 pJ with a bit-select element, designed to achieve a minimum overhead power consumption of about 30%. Individual magnetic memory cells measured at 4 K show reliable switching with write error rates below 10-6, and a 4 × 4 array can be fully addressed with bit select error rates of 10-6. This demonstration is a first step towards a full cryogenic memory architecture targeting energy and performance specifications appropriate for applications in superconducting high performance and quantum computing control systems, which require significant memory resources operating at 4 K.
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Human epidermal growth factor receptor 2-positive (HER2+) breast cancer accounts for â¼20% of invasive breast cancers and is associated with poor prognostics. The recent outcome of HER2+ breast cancer treatment has been vastly improved owing to the application of antibody-targeted therapies. Trastuzumab (Herceptin) is a monoclonal antibody designed to target HER2+ breast cancer cells. In addition to improved survival in the adjuvant treatment of HER2+ breast cancer, trastuzumab treatment has also been associated with cardiotoxicity side effect. However, the molecular mechanisms of trastuzumab action and trastuzumab-mediated cardiotoxicity are still not fully understood. Previous research utilized bulk transcriptomics analysis to study the underlining mechanisms, which relied on averaging molecular signals from bulk tumor samples and might have overlooked key expression features within breast cancer tumor. In contrast to previous research, we compared the single cancer cell level transcriptome profile between trastuzumab-treated and nontreated patients to reveal a more in-depth transcriptome profile. A total of 461 significantly differential expressed genes were identified, including previously defined and novel gene expression signatures. In addition, we found that trastuzumab-enhanced MGP gene expression could be used as prognostics marker for longer patient survival in breast invasive carcinoma patients, and validated our finding using TCGA (The Cancer Genome Atlas) breast cancer dataset. Moreover, our study revealed a 48-gene expression signature that is associated with cell death of cardiomyocytes, which could be used as early biomarkers for trastuzumab-mediated cardiotoxicity. This work is the first study to look at single cell level transcriptome profile of trastuzumab-treated patients, providing a new understanding of the molecular mechanism(s) of trastuzumab action and trastuzumab-induced cardiotoxicity side effects.
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Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/metabolismo , Transcriptoma/efectos de los fármacos , Trastuzumab/uso terapéutico , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/epidemiología , Proteínas de Unión al Calcio/metabolismo , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/epidemiología , Carcinoma Ductal de Mama/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proyectos Piloto , Pronóstico , ARN Mensajero/metabolismo , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Análisis de Supervivencia , Proteína Gla de la MatrizAsunto(s)
Enfermedades de la Conjuntiva/diagnóstico , Histiocitosis de Células de Langerhans/diagnóstico , Enfermedades de la Conjuntiva/cirugía , Crioterapia , Histiocitosis de Células de Langerhans/cirugía , Humanos , Presión Intraocular , Células de Langerhans/patología , Masculino , Agudeza Visual , Adulto JovenRESUMEN
PURPOSE: Low inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrier-based DPIs was investigated. METHODS: Cyclohaler®, Accuhaler® and Easyhaler® were tested with and without the spacers between 30 and 60 Lmin−1. Deposition of particles in the next generation impactor and within the devices was determined by high performance liquid chromatography. RESULTS: Reduced induction port deposition of the emitted particles from the cyclones was observed due to the high retention of the drug within the spacers (e.g. salbutamol sulphate (SS): 67.89 ± 6.51% at 30 Lmin−1 in Cheng 1). Fine particle fractions of aerosol as emitted from the cyclones were substantially higher than the DPIs alone. Moreover, the aerodynamic diameters of particles emitted from the cyclones were halved compared to the DPIs alone (e.g. SS from the Cyclohaler® at 4 kPa: 1.08 ± 0.05 µm vs. 3.00 ± 0.12 µm, with and without Cheng 2, respectively) and unaltered with increased flow rates. CONCLUSION: This work has shown the potential of employing a cyclone spacer for commercial carrier-based DPIs to improve inhaled drug delivery.
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Sistemas de Liberación de Medicamentos , Polvos , Cromatografía Líquida de Alta Presión , Técnicas In Vitro , Tamaño de la PartículaRESUMEN
BACKGROUND: Nicotine has an antinociceptive effect in animal models. The analgesic effect in humans has been examined, but studies have had mixed results. A proposed etiology is variability in chronic nicotine exposure because of differences in tobacco smoking rates and second-hand smoke exposure. In this study, we examined the postoperative analgesic effect of a transdermal nicotine patch in smokers in a parallel design to a previous study in nonsmokers. METHODS: We conducted a randomized, double-blind, prospective, placebo-controlled trial of 28 patients undergoing abdominal or pelvic surgery who required patient-controlled analgesia and an overnight hospital stay. Before anesthetic induction, a transdermal nicotine patch was applied (0, 5, 10, or 15 mg). The primary outcome variable was postoperative pain reported over the first hour and over the next 5 days using a standard numerical rating scale. Secondary outcome variables were pain medication use, hemodynamic values, nausea, and sedation. RESULTS: Patients treated with nicotine reported higher pain scores than those treated with placebo over the first hour after surgery (P < 0.01, average numerical rating scale increase = 0.67) and there was no difference between groups in the subsequent 5 days (P > 0.05). There was no significant dose effect. Diastolic blood pressure in the first hour was higher in the placebo group compared with the nicotine-treated group (P < 0.01, average increase = 11 mm Hg). There was no difference in nausea or sedation. CONCLUSIONS: Transdermal nicotine, 5-15 mg, failed to relieve postoperative pain or reduce opioid use in smokers.
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Analgésicos/administración & dosificación , Nicotina/administración & dosificación , Agonistas Nicotínicos/administración & dosificación , Dolor Postoperatorio/prevención & control , Fumar/efectos adversos , Administración Cutánea , Adulto , Analgesia Controlada por el Paciente , Analgésicos/efectos adversos , Analgésicos Opioides/administración & dosificación , Formas de Dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morfina/administración & dosificación , Nicotina/efectos adversos , Agonistas Nicotínicos/efectos adversos , Dimensión del Dolor , Dolor Postoperatorio/etiología , Proyectos Piloto , Estudios Prospectivos , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
Orbital myositis is an extremely rare extra-intestinal manifestation of Crohn's disease. Herein we describe a patient with self-limiting episodes of episcleritis and uveitis prior to the diagnosis of Crohn's disease, and subsequent development of recurrent orbital myositis with radiological features mimicking thyroid eye disease.
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Enfermedad de Crohn/complicaciones , Enfermedad de Graves/diagnóstico por imagen , Miositis Orbitaria/diagnóstico por imagen , Miositis Orbitaria/etiología , Adulto , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Diagnóstico Diferencial , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/administración & dosificación , Imagen por Resonancia Magnética , Mercaptopurina/administración & dosificación , Metilprednisolona/uso terapéutico , Músculos Oculomotores/diagnóstico por imagen , Músculos Oculomotores/patología , Miositis Orbitaria/tratamiento farmacológico , Recurrencia , Escleritis/diagnóstico , Escleritis/tratamiento farmacológico , Escleritis/etiología , Tomografía Computarizada por Rayos X , Uveítis Anterior/diagnóstico , Uveítis Anterior/tratamiento farmacológico , Uveítis Anterior/etiologíaRESUMEN
An extreme premature infant born at 25 weeks post menstrual age (PMA) presented at PMA of 32 weeks with non-multiresistant methicillin resistant Staphylococcus aureus (MRSA) Pott's puffy tumor (PPT) involving both orbital and intracranial extension is described here. This is the youngest case of PPT ever reported in the antibiotic era.
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Absceso/microbiología , Sinusitis Frontal/microbiología , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Enfermedades Orbitales/microbiología , Osteomielitis/microbiología , Infecciones Estafilocócicas/microbiología , Absceso/diagnóstico , Absceso/tratamiento farmacológico , Antibacterianos/uso terapéutico , Clindamicina/uso terapéutico , Drenaje/métodos , Sinusitis Frontal/diagnóstico , Sinusitis Frontal/tratamiento farmacológico , Edad Gestacional , Humanos , Recien Nacido con Peso al Nacer Extremadamente Bajo , Recién Nacido , Recien Nacido Prematuro , Imagen por Resonancia Magnética , Masculino , Enfermedades Orbitales/diagnóstico , Enfermedades Orbitales/tratamiento farmacológico , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Tomografía Computarizada por Rayos XRESUMEN
An extended computational model of the circulatory system has been developed to predict blood flow in the presence of ventricular assist devices (VADs). A novel VAD, placed in the descending aorta, intended to offload the left ventricle (LV) and augment renal perfusion is being studied. For this application, a better understanding of the global hemodynamic response of the VAD, in essence an electrically driven pump, and the cardiovascular system is necessary. To meet this need, a model has been established as a nonlinear, lumped-parameter electrical analog, and simulated results under different states [healthy, congestive heart failure (CHF), and postinsertion of VAD] are presented. The systemic circulation is separated into five compartments and the descending aorta is composed of three components to accurately yield the system response of each section before and after the insertion of the VAD. Delays in valve closing time and blood inertia in the aorta were introduced to deliver a more realistic model. Pump governing equations and optimization are based on fundamental theories of turbomachines and can serve as a practical initial design point for rotary blood pumps. The model's results closely mimic established parameters for the circulatory system and confirm the feasibility of the intra-aortic VAD concept. This computational model can be linked with models of the pump motor to provide a valuable tool for innovative VAD design.
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Fenómenos Fisiológicos Cardiovasculares , Corazón Auxiliar , Hemodinámica/fisiología , Modelos Cardiovasculares , Diseño de Prótesis , AlgoritmosRESUMEN
BACKGROUND: Nicotine has been shown to be antinociceptive in the postoperative period in animal studies. Human studies with nasal nicotine sprays have had mixed results, possibly due to variability in pharmacokinetics and potential patient variables such as exposure to nicotine in tobacco smokers. In this pilot study, we examined the analgesic effect of a transdermal nicotine patch applied before surgery in nonsmokers. METHODS: We conducted a randomized, double-blind, prospective placebo-controlled trial of 40 subjects, undergoing general surgery that required postoperative patient-controlled analgesia and an overnight hospital admission. Immediately before surgery, a transdermal nicotine patch containing 0, 5, 10, or 15 mg was applied. The primary outcome variable was pain report using a numerical rating scale (NRS) in the first hour after surgery and over the next 5 days. Secondary outcomes were pain medication use, hemodynamic values, nausea, and sedation. RESULTS: Patients treated with nicotine reported lower pain scores when compared with those treated with placebo during the first hour after surgery (P = 0.003, average NRS decrease = 1.4, 95% CI = 0.3-2.6) and for 5 days after surgery (P = 0.03, average NRS decrease = 1.0, 95% CI = 0.1-1.9). There was no increased benefit of nicotine with doses larger than 5 mg. There was a trend suggesting decreased pain medicine use, increased nausea, decreased tachycardia, and slightly decreased systolic blood pressure in the nicotine groups, but these values did not reach significance. CONCLUSIONS: Transdermal nicotine, 5-15 mg, reduced postoperative pain scores but failed to decrease the need for opioid analgesics or opioid-related side effects after general surgical procedures.
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Administración Cutánea , Analgésicos/administración & dosificación , Nicotina/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Nicotina/uso terapéutico , Proyectos Piloto , Placebos , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Preclinical studies have suggested that some volatile anesthetics induce a hyperalgesic state that may be secondary to nicotinic inhibition. A previous trial of treatment with nicotine nasal spray demonstrated postoperative analgesia in women anesthetized with isoflurane. To determine whether the effect of nicotine was reversing hyperalgesia induced by isoflurane, or simply acting as an analgesic, we studied the effect of nicotine on postoperative pain in women anesthetized with isoflurane or propofol, with fentanyl. METHODS: In a randomized, prospective, double-blind trial, we assigned 80 women having open uterine surgery to be anesthetized with isoflurane or propofol. Within each anesthetic group, the subjects were further randomly assigned to receive nicotine 3 mg or placebo. Pain reported with a numerical analog scale was the primary outcome variable. RESULTS: The patient demographics were similar. Women who were anesthetized with propofol reported less pain and used less morphine during the first day after surgery than women who were anesthetized with isoflurane (P < 0.01, P < 0.01). Nicotine treatment did not change pain report or morphine use in either anesthetic group (P > 0.05). CONCLUSIONS: General anesthesia with propofol and is associated with less postoperative pain and morphine use than general anesthesia with isoflurane. Nicotine was not analgesic in this trial. If these results are repeated in other populations, reduced postoperative pain can be added to the previously described improvement in nausea and vomiting as a potential benefit of anesthesia with propofol.