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1.
ESMO Open ; 9(8): 103663, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39146670

RESUMEN

BACKGROUND: First-line zolbetuximab plus chemotherapy (SPOTLIGHT, mFOLFOX6; GLOW, CAPOX) significantly improved progression-free survival (PFS) and overall survival (OS) versus placebo plus chemotherapy in patients with human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors were claudin 18 isoform 2-positive in the phase III SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies. We present patient-reported outcomes (PROs) from these studies. MATERIALS AND METHODS: Health-related quality of life (HRQoL) was measured in the full analysis sets using the European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients Core Questionnaire (QLQ-C30) and Oesophago-Gastric Module (QLQ-OG25), Global Pain, and 5-level EQ-5D (EQ-5D-5L) questionnaires. Analyses focused on key PRO domains: global health status (GHS)/QoL, physical functioning, abdominal pain and discomfort, and nausea/vomiting. Least squares mean (LSM) changes from baseline and time to first definitive deterioration (TTDD) were evaluated combined across SPOTLIGHT and GLOW and for individual studies. Time to confirmed deterioration (TTCD) was evaluated independently for SPOTLIGHT and GLOW. RESULTS: The combined analysis set included 1072 patients (zolbetuximab plus chemotherapy, 537; placebo plus chemotherapy, 535). Compliance rates were similar between treatment arms. Similar trends were observed in the zolbetuximab versus placebo arms for LSM changes from baseline in key PRO domains, with no clinically meaningful deterioration. Nausea/vomiting worsened during the first few zolbetuximab cycles but later returned to baseline levels. Overall TTCD and TTDD results were similar between arms in both studies. CONCLUSIONS: Patients in SPOTLIGHT and GLOW maintained measured HRQoL relative to baseline when treated with first-line zolbetuximab added to chemotherapy. Zolbetuximab plus chemotherapy improved PFS and OS without negatively affecting HRQoL in key PRO domains compared with placebo plus chemotherapy.


Asunto(s)
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Unión Esofagogástrica , Calidad de Vida , Neoplasias Gástricas , Humanos , Adenocarcinoma/tratamiento farmacológico , Unión Esofagogástrica/patología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Masculino , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Neoplasias Esofágicas/tratamiento farmacológico , Anciano , Medición de Resultados Informados por el Paciente , Fluorouracilo/uso terapéutico , Adulto , Leucovorina/uso terapéutico , Encuestas y Cuestionarios , Compuestos Organoplatinos/uso terapéutico , Claudinas
2.
Rev Sci Instrum ; 94(6)2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37862489

RESUMEN

This paper reports an indigenously developed probe for the measurement of spatial profiles of the absorbed/generated RF power density Pabs (W/m3) in RF discharges. The technique utilizes a calibrated current (J) probe based on the Rogowski coil principle and an electric field (E) probe based on capacitive coupling, both integrated into a single probe called the J.E probe. Various aspects of the probe, such as its design, fabrication, calibration, and limitations, were resolved before it was used for obtaining axial profiles of RF power absorption/generation. Also presented are the first experimental results for the absorbed power density profiles at the fundamental (13.56 MHz) and harmonic (27.12 MHz) along the length of a capacitively coupled discharge. The axial scans between the powered and grounded electrode were taken at different argon gas pressures (10-800 mTorr) at a fixed RF power of 10 W. Detailed analysis of the results shows that even for systems with large electrode gaps, i.e., plasmas with long bulk plasma regions, practically all the fundamental power is absorbed in a narrow edge region near the powered electrode, irrespective of the pressure. Absorption is high near the RF electrode since the RF fields peak in this region. Another important conclusion is that stochastic absorption of the fundamental and harmonic generation proceeds fairly efficiently in the vicinity of the powered electrode even at high pressures. It may be mentioned that the probe technique introduced here is the first of its kind, and although there is considerable scope for miniaturization, it has, nonetheless, provided some key insights into the nature of RF power absorption in capacitive discharges.

3.
Rev Sci Instrum ; 93(12): 123514, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36586948

RESUMEN

This paper presents a joint calibration scheme for voltage (V) and current (I) probes that helps accurately resolve the voltage-current phase differences even when the difference is very close to 90°. The latter has been a major issue with V-I probes when used with miniature RF plasma devices such as the atmospheric pressure plasma jet (APPJ). Since the impedance of such miniature devices is predominantly capacitive, the phase difference between the voltage and current signals is very nearly 90°. It turns out, however, that when V-I probes are used with such devices without joint calibration, these frequently yield phase shifts over 90°. Also, since the power absorption is proportional to the resistive part of the impedance, it becomes very sensitive to the phase difference when it is close to ≈90°. Thus, it is important to be able to accurately resolve the phases. Post-calibration, V-I probes would be indispensable for the electrical characterization of APPJs for determining the average RF power Pav, plasma impedance Zp, etc. Typical post-calibration V-I data yield Zp ≈ 93.6 - j 1139 Ω (81.5 - j 1173 Ω) at Pav ≈9.8W (≈7.7W) for helium (argon) gas.

4.
ESMO Open ; 7(3): 100510, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35714477

RESUMEN

BACKGROUND: To date, the efficacy of the androgen receptor inhibitors enzalutamide and apalutamide for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) has not been compared directly in a clinical trial setting. Indirect comparisons can be used to assess relative efficacy and provide important information to guide treatment decisions. PROSPER and SPARTAN were double-blind, randomized, placebo-controlled, phase III trials in patients with nmCRPC with overall similar study designs and inclusion and exclusion criteria. Using an anchored matching-adjusted indirect comparison, based on the final data from the PROSPER and SPARTAN studies, we assessed the comparative efficacy of enzalutamide and apalutamide, both plus androgen deprivation therapy. METHODS: Using placebo as the common comparator, individual patient data from PROSPER were matched to the aggregate patient data from SPARTAN and efficacy endpoints from PROSPER were re-weighted accordingly. Patient baseline characteristics and endpoints were clinically and statistically tested to identify potential effect modifiers, according to National Institute for Health and Care Excellence guidelines. Hazard ratios for overall survival (OS), metastasis-free survival (MFS), and time to chemotherapy (TTCx) were re-estimated for PROSPER using weighted Cox proportional hazards models and indirectly compared with those of SPARTAN using a Bayesian network meta-analysis. RESULTS: Estimated hazard ratios [95% credible interval (CrI)] for enzalutamide versus apalutamide were 0.80 (95% CrI 0.58-1.10) for OS, 0.94 (95% CrI 0.69-1.29) for MFS2, and 0.90 (95% CrI 0.63-1.29) for TTCx. Similar results were seen for sensitivity analyses conducted for OS and MFS. Bayesian probability analyses showed a 91.7% favoring enzalutamide for OS, 65.1% for MFS, and 71.4% for TTCx. CONCLUSIONS: The results of this matching-adjusted indirect comparison of final data from PROSPER and SPARTAN indicate comparable efficacy of enzalutamide and apalutamide with potentially a greater probability of longer MFS, OS, and TTCx in patients with nmCRPC treated with enzalutamide versus apalutamide.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Antagonistas de Andrógenos/uso terapéutico , Teorema de Bayes , Benzamidas , Ensayos Clínicos Fase III como Asunto , Humanos , Masculino , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Tiohidantoínas , Resultado del Tratamiento
5.
J Eur Acad Dermatol Venereol ; 35(11): 2324-2330, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34014011

RESUMEN

BACKGROUND: Several clinician-rated scoring systems are available to assess nail psoriasis severity, but only one has been partially validated. OBJECTIVE: To develop and validate the Physician's Global Assessment of Fingernail Psoriasis (PGA-F), a new clinician-rated severity scale. METHODS: A literature review, concept elicitation, pilot cognitive debriefing and clinical expert consultations informed the development of the PGA-F. A multistage mixed-methods analysis consisted of practising dermatologist cognitive interviews (n = 10) for instrument clarity, relevance and comprehensiveness. Inter-rater reliability (IRR) of ratings from dermatologists (n = 22) and clinical trial investigators (n = 8) was tested using many-facet Rasch analysis. Concurrent validity between the PGA-F and modified Nail Psoriasis Severity Index (mNAPSI) at screening and baseline was assessed along with the degree of discrimination. Intraclass correlation coefficient (ICC) for single raters at multiple assessments determined IRR. RESULTS: The PGA-F synthesizes severity ratings across multiple disease features that classify individuals into 1 of 5 levels (clear to severe). Cognitive interviews confirmed content validity: all (n = 10, 100%) participants who agreed clinical criteria were consistent with nail psoriasis; no mismatched severity levels; and training photographs were realistic representations. All PGA-F items were locally independent and targeted patients along the severity continuum with complementary precision (item fit statistics: < the 1.5 acceptability threshold; exact agreements among the dermatologists [44%] and trial investigators [61.5%] exceeded 40% of acceptability threshold). Clinician reliability exceeded the threshold of acceptability for dermatologists and clinical trial investigators: 0.85 and 0.73, respectively. There was adequate correlation (>0.30) between mNAPSI and PGA-F at baseline and Week 26 with significant discrimination of severity and monotonic increases in the mNAPSI for each level of categorical severity on the PGA-F. ICC results for each type of IRR indicate that clinicians were consistent in individual patient ratings. CONCLUSION: The PGA-F is a rapid, valid and reliable clinician-rated severity scale for use in clinical practice and research.


Asunto(s)
Médicos , Psoriasis , Humanos , Uñas , Psoriasis/diagnóstico , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad
6.
Sci Adv ; 7(17)2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33893093

RESUMEN

Existing three-dimensional (3D) culture techniques are limited by trade-offs between throughput, capacity for high-resolution imaging in living state, and geometric control. Here, we introduce a modular microscale hanging drop culture where simple design elements allow high replicates for drug screening, direct on-chip real-time or high-resolution confocal microscopy, and geometric control in 3D. Thousands of spheroids can be formed on our microchip in a single step and without any selective pressure from specific matrices. Microchip cultures from human LN229 glioblastoma and patient-derived mouse xenograft cells retained genomic alterations of originating tumors based on mate pair sequencing. We measured response to drugs over time with real-time microscopy on-chip. Last, by engineering droplets to form predetermined geometric shapes, we were able to manipulate the geometry of cultured cell masses. These outcomes can enable broad applications in advancing personalized medicine for cancer and drug discovery, tissue engineering, and stem cell research.


Asunto(s)
Ensayos Analíticos de Alto Rendimiento , Esferoides Celulares , Animales , Técnicas de Cultivo de Célula/métodos , Evaluación Preclínica de Medicamentos , Ensayos Analíticos de Alto Rendimiento/métodos , Humanos , Ratones , Ingeniería de Tejidos/métodos
7.
Rev Sci Instrum ; 91(9): 094705, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-33003791

RESUMEN

An accurate, non-invasive ex situ diagnostic technique for analyzing plasma generated harmonics in radio frequency (RF) discharges is presented utilizing a broadband Dual Directional Coupler (DDC) that measures accurately both forward and reflected voltage signals in a transmission line. For usual applications such as monitoring forward and reflected power, the DDC is placed between the RF generator and the matching network (MN). However, the MN reflects all plasma generated harmonics back toward the plasma. Hence, no harmonics reach the generator side of the MN. Thus, for monitoring the harmonics, it is necessary to place the DDC between the impedance matching unit and the plasma, which was used for the first time in an asymmetric, parallel plate RF discharge at 13.56 MHz, 10 W-50 W at 200 mTorr (argon). The analysis of DDC data yields voltage, harmonic power contents, complex load impedance, plasma reflection coefficient, Voltage Standing Wave Ratio (VSWR), etc., for the fundamental frequency. For instance, at 10 W net input power, the computed plasma impedance is ZL = Rp + jXp, with Rp = 16.8 Ω and Xp = -81.9 Ω, yielding VSWR ≈11. Additionally, for 50 W input power, the third harmonic (72.31 mW) is dominant, followed by the second (8.28 mW) and fourth harmonics. In contrast, the literature states that the second harmonic is usually dominant, possibly due to the invasive nature of the diagnostics. Because harmonics are an important signature of processes taking place within the plasma, the proposed diagnostic can be effectively used for calibration and verification of theoretical models/simulations for resolving relevant physics issues.

8.
bioRxiv ; 2020 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-32511358

RESUMEN

The COVID-19 pandemic provides an urgent example where a gap exists between availability of state-of-the-art diagnostics and current needs. As assay details and primer sequences become widely known, many laboratories could perform diagnostic tests using methods such as RT-PCR or isothermal RT-LAMP amplification. A key advantage of RT-LAMP based approaches compared to RT-PCR is that RT-LAMP is known to be robust in detecting targets from unprocessed samples. In addition, RT-LAMP assays are performed at a constant temperature enabling speed, simplicity, and point-of-use testing. Here, we provide the details of an RT-LAMP isothermal assay for the detection of SARS-CoV-2 virus with performance comparable to currently approved tests using RT-PCR. We characterize the assay by introducing swabs in virus spiked synthetic nasal fluids, moving the swab to viral transport medium (VTM), and using a volume of that VTM for performing the amplification without an RNA extraction kit. The assay has a Limit-of-Detection (LOD) of 50 RNA copies/µL in the VTM solution within 20 minutes, and LOD of 5000 RNA copies/µL in the nasal solution. Additionally, we show the utility of this assay for real-time point-of-use testing by demonstrating detection of SARS-CoV-2 virus in less than 40 minutes using an additively manufactured cartridge and a smartphone-based reader. Finally, we explore the speed and cost advantages by comparing the required resources and workflows with RT-PCR. This work could accelerate the development and availability of SARS-CoV-2 diagnostics by proving alternatives to conventional laboratory benchtop tests.

9.
J Hazard Mater ; 374: 140-151, 2019 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-30991166

RESUMEN

The distinctive and tuneable physical, chemical and configurational properties of carbon nanotubes (CNTs), has prompted their combination with metal oxides to contrive carbon composites showing entrancing adsorption property with incredible potential in water treatment. MWCNT/Alumina (RMAC) nodules with effective adsorption capacity were synthesized following aqueous sol-gel route. Batch sorption experiments examined the efficiency of removal of dyes and heavy metal ions from an aqueous solution on RMAC nodules. The factors affecting adsorption were studied for adsorption of methylene blue dye (MB) and hexavalent chromium by altering the MWCNT concentration from 1 wt.% to 5 wt.%. The adsorption experiment demonstrated an adsorption capacity of 187.5 and 597 mg g-1 at 25 °C for MB and Cr (VI) respectively. Various characterization techniques such as XRD, BET, TEM, Raman, FTIR, TPD and CHN were employed to study the initial development of the material. Multiple adsorption interaction mechanisms (electrostatic interactions, hydrogen bonding, π-π electron-donor-acceptor interactions) may be credited for the remarkable adsorption capacity of these nodules. Results of this work are of great significance for environmental applications of Alumina/MWCNT composite as a promising adsorbent nanomaterial for organic pollutants from aqueous solutions. Apart from high sorption ability, these nodules offer ease of separation with splendid regeneration ability.

10.
J Eur Acad Dermatol Venereol ; 32(12): 2254-2256, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29959796

RESUMEN

BACKGROUND: Hidradenitis suppurativa clinical response (HiSCR) is a validated clinical end point for measuring response to treatment in patients with hidradenitis suppurativa (HS). Previous studies have reported on the validity, responsiveness and meaningfulness of the HiSCR. OBJECTIVE: To evaluate the HiSCR for inter- and intrarater reliability characteristics. METHODS: A stand-alone, two-site, prospective, non-interventional observational study consisted of 22 patients, with self-reported severity between mild, moderate and severe HS. The Patient Global Impression of Change (PGI-C) scale was completed by patients at Timepoint 2. Descriptive statistics of Hurley Stage, total abscesses, total draining fistulas, total inflammatory nodules and total AN count (sum of inflammatory nodules and lesions) were reported at two timepoints. Inter-rater reliability and intrarater reliability for the HS lesion count tool were evaluated at two timepoints (baseline and Day 7) using the HS lesion count tool. Intraclass correlation (ICC) coefficients of lesion counts were calculated to evaluate inter- and intrarater reliability of lesion counts between pairs of dermatologists. RESULTS: The majority of patients demonstrated either no change or minimally worse PGI-C in HS scores. Descriptive statistics were similar between rater groups and timepoints assessed. Inter-rater ICC coefficients for abscess count at Timepoints 1 and 2 were 0.38 and 0.67. The ICC coefficients for draining fistula and AN count were ≥0.61 at both timepoints. In an exploratory model, ICC coefficients were ≥0.68 for all evaluated lesion counts. The test-retest reliability using ICC coefficients was ≥0.70 for total abscess, draining fistula, inflammatory nodule and AN count. CONCLUSION: The HS lesion count tool had an acceptable inter- and intrarater reliability, indicating that HiSCR has a strong degree of reproducibility and consistency in the evaluation of patients with HS.


Asunto(s)
Absceso/etiología , Fístula Cutánea/etiología , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/terapia , Adolescente , Adulto , Anciano , Determinación de Punto Final , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estudios Prospectivos , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto Joven
11.
Nat Commun ; 9(1): 202, 2018 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-29335461

RESUMEN

Here, we present a technique that performs on-chip picoliter real-time reverse transcriptase loop mediated isothermal amplification (RT-LAMP) reactions on a histological tissue section without any analyte purification while preserving the native spatial location of the nucleic acid molecules. We demonstrate this method by amplifying TOP2A messenger RNA (mRNA) in a prostate cancer xenograft with 100 µm spatial resolution and by visualizing the variation in threshold time of amplification across the tissue. The on-chip reaction was validated by mRNA fluorescence in situ hybridization (mFISH) from cells in the tissue section. The entire process, from tissue loading on microchip to results from RT-LAMP can be carried out in less than 2 h. We anticipate that this technique, with its ease of use, fast turnaround, and quantitative molecular outputs, would become an invaluable tissue analysis tool for researchers and clinicians in the biomedical arena.


Asunto(s)
Perfilación de la Expresión Génica , Neoplasias de la Próstata/genética , Animales , Línea Celular Tumoral , ADN-Topoisomerasas de Tipo II/genética , Xenoinjertos , Humanos , Hibridación Fluorescente in Situ , Masculino , Ratones , Ratones Desnudos , Procedimientos Analíticos en Microchip , Proteínas de Unión a Poli-ADP-Ribosa/genética , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Espectroscopía Infrarroja por Transformada de Fourier
12.
Biomed Microdevices ; 19(4): 73, 2017 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-28831630

RESUMEN

Infectious diseases remain the world's top contributors to death and disability, and, with recent outbreaks of Zika virus infections there has been an urgency for simple, sensitive and easily translatable point-of-care tests. Here we demonstrate a novel point-of-care platform to diagnose infectious diseases from whole blood samples. A microfluidic platform performs minimal sample processing in a user-friendly diagnostics card followed by real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) on the same card with pre-dried primers specific to viral targets. Our point-of-care platform uses a commercial smartphone to acquire real-time images of the amplification reaction and displays a visual read-out of the assay. We apply this system to detect closely related Zika, Dengue (types 1 and 3) and Chikungunya virus infections from whole blood on the same pre-printed chip with high specificity and clinically relevant sensitivity. Limit of detection of 1.56e5 PFU/mL of Zika virus from whole blood was achieved through our platform. With the ability to quantitate the target nucleic acid, this platform can also perform point-of-care patient surveillance for pathogen load or select biomarkers in whole blood.


Asunto(s)
Fiebre Chikungunya , Dengue , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas/métodos , Técnicas de Amplificación de Ácido Nucleico , Sistemas de Atención de Punto , Teléfono Inteligente , Infección por el Virus Zika , Fiebre Chikungunya/sangre , Fiebre Chikungunya/diagnóstico , Virus Chikungunya , Dengue/sangre , Dengue/diagnóstico , Virus del Dengue , Humanos , Técnicas de Amplificación de Ácido Nucleico/instrumentación , Técnicas de Amplificación de Ácido Nucleico/métodos , Virus Zika , Infección por el Virus Zika/sangre , Infección por el Virus Zika/diagnóstico
13.
Indian J Nephrol ; 27(1): 74-77, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28182047

RESUMEN

Gitelman's syndrome (GS) is a rare autosomal recessive disorder caused by mutations in thiazide-sensitive NaCl cotransporter. We report a 49-year-old, normotensive lady with prolonged hypokalemia since her 20s who was diagnosed with GS at our renal clinic. During follow-up, she was found to have mild, asymptomatic, euvolemic hyponatremia with low serum uric acid, inappropriately high urine osmolality and sodium consistent with syndrome of inappropriate antidiuretic hormone-like presentation. Despite life-long urinary sodium losses, hyponatremia has rarely been reported in GS to be due to the primary disease process. We present relevant clinical data and hypothesize on why this disease per se may be a risk factor for dilutional hyponatremia.

14.
Sci Rep ; 6: 37527, 2016 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-27892482

RESUMEN

We have carried out detailed magnetic and transport studies of the new Sr0.5Ce0.5FBiS2-xSex (0.0 ≤ x ≤ 1.0) superconductors derived by doping Se in Sr0.5Ce0.5FBiS2. Se-doping produces several effects: it suppresses semiconducting-like behavior observed in the undoped Sr0.5Ce0.5FBiS2, the ferromagnetic ordering temperature, TFM, decreases considerably from 7.5 K (in Sr0.5Ce0.5FBiS2) to 3.5 K and the superconducting transition temperature, Tc, gets enhanced slightly to 2.9-3.3 K. Thus in these Se-doped materials, TFM is marginally higher than Tc. Magnetization studies provide evidence of bulk superconductivity in Sr0.5Ce0.5FBiS2-xSex at x ≥ 0.5 in contrast to the undoped Sr0.5Ce0.5FBiS2 (x = 0) where magnetization measurements indicate a small superconducting volume fraction. Quite remarkably, as compared with the effective paramagnetic Ce-moment (~2.2 µB), the ferromagnetically ordered Ce-moment in the superconducting state is rather small (~0.1 µB) suggesting itinerant ferromagnetism. To the best of our knowledge, Sr0.5Ce0.5FBiS2-x Sex (x = 0.5 and 1.0) are distinctive Ce-based bulk superconducting itinerant ferromagnetic materials with Tc < TFM. Furthermore, a novel feature of these materials is that they exhibit a dual and quite unusual hysteresis loop corresponding to both the ferromagnetism and the coexisting bulk superconductivity.

15.
J Clin Pharm Ther ; 40(4): 466-71, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26032753

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Clinical practice in the initiation, prescribing, dosing and monitoring of warfarin in the UK varies, but this has not been adequately documented. The objective was to undertake a survey on current clinical practice in this area, and how it compares with national guidelines that have been developed by the British Committee for Standards in Haematology. METHODS: A national online survey of anticoagulation clinics was performed using Survey Monkey(®) . The survey was designed to capture data for prescribing, dosing and monitoring of anticoagulation with warfarin. RESULTS: Of 85 clinics who responded to the survey, most were run by secondary care (68%), facilitated by specialist nurses (58%) and followed standard guidelines for the management of warfarin (87%). The majority of clinics indicated their target international normalized ratio (INR) for patients with atrial fibrillation (AF) (69/73; 94·5%) was between 2·0 and 3·0, but the indicated target INR for mechanical heart valves was more variable. Initiation and loading dosing regimens were a major source of variability with uncertainty surrounding individual patient factors such as age, ethnicity and BMI. WHAT IS NEW AND CONCLUSIONS: Current practice amongst UK anticoagulation clinics largely follows current national guidelines but better guidance on dosing, taking into account factors that determine interindividual variability in daily warfarin dose requirements would improve and standardize oral anticoagulation with warfarin.


Asunto(s)
Anticoagulantes/administración & dosificación , Monitoreo de Drogas/métodos , Guías de Práctica Clínica como Asunto , Warfarina/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Encuestas de Atención de la Salud , Humanos , Relación Normalizada Internacional , Pautas de la Práctica en Medicina/estadística & datos numéricos , Reino Unido
16.
Ann Clin Biochem ; 51(Pt 4): 503-6, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24150482

RESUMEN

BACKGROUND: Inhaled steroids are widely used for the treatment of asthma. Concerns over adrenal suppression when used at high doses or in combination with drugs such as ritonavir exist, requiring the measurement of serum cortisol. Herein, we investigate the cross-reactivity of the inhaled steroids betamethasone, fluticasone and beclomethasone in the Roche cortisol immunoassay, in addition to five other steroids. METHODS: Five replicates were produced from a serum pool for each of the eight steroids at a final concentration of 0.1 and 1 µg/mL. Each steroid was dissolved in 50% methanol, with 50% methanol of the same volume added to the control sample. The cross-reactivity of each steroid in the cortisol assay was calculated. RESULTS: There was no statistically or clinically significant cross-reactivity in the measurement of cortisol when fluticasone, beclomethasone or betamethasone were spiked at 0.1 and 1.0 µg/mL, except for beclomethasone at a concentration of 1 µg/mL (1490 nmol/L) with a cross-reactivity of 1.6%, which is unlikely to be clinically significant. At both steroid concentrations investigated, prednisolone, 17-hydroxyprogesterone and 11-deoxycortisol exhibited statistically significant cross-reactivities that were greater than the least significant change of the assay (13.1%), whereas dexamethasone and metyrapone did not. Mean inter-assay precision was 1.5% (405-1586 nmol/L). CONCLUSION: The cross-reactivity of the inhaled steroids; betamethasone, fluticasone and beclomethasone in the Roche cortisol immunoassay are unlikely to be clinically significant at the concentrations found in patients on therapeutic doses. This will enable confident assessment of adrenal status in patients at risk of adrenal suppression.


Asunto(s)
Androstadienos/farmacocinética , Antiasmáticos/farmacocinética , Beclometasona/farmacocinética , Betametasona/farmacocinética , Hidrocortisona/sangre , Administración por Inhalación , Administración Oral , Androstadienos/administración & dosificación , Antiasmáticos/administración & dosificación , Beclometasona/administración & dosificación , Betametasona/administración & dosificación , Reacciones Cruzadas , Inhibidores del Citocromo P-450 CYP3A/administración & dosificación , Inhibidores del Citocromo P-450 CYP3A/farmacocinética , Femenino , Fluticasona , Humanos , Inmunoensayo/instrumentación , Inmunoensayo/métodos , Masculino , Ritonavir/administración & dosificación , Ritonavir/farmacocinética
17.
J Appl Microbiol ; 116(3): 511-8, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24268027

RESUMEN

AIMS: Microbial exopolymer with antimicrobial properties, in particular, has gathered considerable interest due to their enormous scope of modification and wide gamut of application. The purpose of present study was to evaluate the antibacterial spectrum of a chemically modified biopolymeric flocculant produced by Klebsiella terrigena. METHODS AND RESULTS: N,N,N trimethyl biopolymer (TMB) was synthesized using dimethyl sulfate as methylating agent and was characterized by nuclear magnetic resonance and mass spectroscopic analysis, which confirmed the presence of quaternary ammonium groups on the TMB structure. The antibacterial activity of TMB was investigated against three selected bacterial pathogens viz. Aeromonas hydrophila ATCC 35654, Listeria monocytogenes ATCC 19111 and Escherichia coli O157:H7 ATCC 32150. An inactivation of 3 log CFU ml(-1) of all pathogens was noticed for TMB when compared to native polymer over a short contact time (60 min) and low dosage (60-80 µg ml(-1) ) at ambient temperature. A marked increase in glucose level, protein content and lactate dehydrogenase (LDH) activity was observed concurrently in the cell supernatant suggesting damage of the cell membranes to be a possible reason for inactivation. CONCLUSIONS: The quaternization of amino rich biopolymer isolated from a bacterium led to a water-soluble bioactive agent with enhanced inhibitive capability against all the selected bacterial pathogens. SIGNIFICANCE AND IMPACT OF STUDY: The results of this study suggest a potential application of TMB as an effective disinfectant in water treatment.


Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Biopolímeros/química , Biopolímeros/farmacología , Klebsiella/metabolismo , Aeromonas hydrophila/efectos de los fármacos , Antibacterianos/biosíntesis , Biopolímeros/biosíntesis , Desinfectantes/química , Desinfectantes/metabolismo , Desinfectantes/farmacología , Escherichia coli O157/efectos de los fármacos , Floculación , Listeria monocytogenes/efectos de los fármacos , Datos de Secuencia Molecular
18.
Work ; 43(4): 453-8, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23151735

RESUMEN

OBJECTIVE: The 'saree' worn by women in India and many South Asian countries is dyed using a tub, usually in small scale units employing low capital and a small number of workers. While using these tubs, workers adopt awkward postures over long periods of time which results in severe discomfort in the neck, shoulders and lower extremities. The purpose of the study was to redesign the dyeing tub using a participatory approach and to study the impact of the newly designed tub on the reported body discomfort and rate of production. METHODS: Redesigning of the dyeing tub was carried out using three parallel participative processes--(1) eliciting the views of workers who use the tub, (2) interacting with the proprietors of the small scale dyeing units (the employers) and the tub manufacturers, and (3) iterative prototype tub development based on inputs from the first two processes. These processes facilitated involvement of the stake-holders and the acceptance of change. The final prototype was tested by nine workers for a period of three months to evaluate the reduction in body discomfort and increase in rate of production (output). RESULTS: Studies on the impact of the new tub showed a reduction in discomfort level from 'severe' to 'moderate', and a mean increase of 7.9% in the output, confirming the benefits of the participative approach to ergonomics intervention. The involvement, trust and credibility generated by the participative process facilitated the acceptance of the final design.


Asunto(s)
Participación de la Comunidad , Eficiencia , Ergonomía/métodos , Dolor de la Región Lumbar/prevención & control , Dolor de Cuello/prevención & control , Enfermedades Profesionales/prevención & control , Adulto , Vestuario , Colorantes , Femenino , Humanos , India , Industrias/instrumentación , Dolor de la Región Lumbar/psicología , Dolor de Cuello/psicología , Enfermedades Profesionales/psicología , Salud Laboral , Innovación Organizacional , Postura , Factores de Riesgo , Lugar de Trabajo
19.
Ultrasonics ; 51(8): 911-20, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21676425

RESUMEN

This paper presents a parametric study on the efficiency of ultrasound focusing in an attenuative medium, using phased arrays. Specifically, an analytical model of ultrasound wave focusing in a homogeneous, isotropic and attenuative fluid with point sources is presented. Calculations based on the model have shown that in an attenuative medium, an optimum frequency exists for the best focusing performance for a particular size of aperture and focal distance. The effect of different f numbers on the focusing performance in the attenuative medium is further investigated. The information obtained from the analytical model provides insights into the design and installation of a phased transducer array for energy efficient wave focusing.

20.
J Phys Condens Matter ; 22(25): 255402, 2010 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-21393798

RESUMEN

We report temperature-dependent Raman spectra of CeFeAsO(0.9)F(0.1) from 4 to 300 K in the spectral range of 60-1800 cm(-1) and interpret them using estimates of phonon frequencies obtained from first-principles density functional calculations. We find evidence for strong coupling between the phonons and crystal field excitations; in particular the Ce(3 + ) crystal field excitation at 432 cm(-1) couples strongly with the E(g) oxygen vibration at 389 cm(-1). Below the superconducting transition temperature, the phonon mode near 280 cm(-1) shows softening, signaling its coupling with the superconducting gap. The ratio of the superconducting gap to T(c), thus estimated to be ~10, suggests CeFeAsO(0.9)F(0.1) to be a strong coupling superconductor. In addition, two high frequency modes observed at 1342 and 1600 cm(-1) are attributed to electronic Raman scattering from the (x(2)-y(2)) to xz /yz d-orbitals of Fe.

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