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The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.
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The mass of the W boson, a mediator of the weak force between elementary particles, is tightly constrained by the symmetries of the standard model of particle physics. The Higgs boson was the last missing component of the model. After observation of the Higgs boson, a measurement of the W boson mass provides a stringent test of the model. We measure the W boson mass, MW, using data corresponding to 8.8 inverse femtobarns of integrated luminosity collected in proton-antiproton collisions at a 1.96 tera-electron volt center-of-mass energy with the CDF II detector at the Fermilab Tevatron collider. A sample of approximately 4 million W boson candidates is used to obtain [Formula: see text], the precision of which exceeds that of all previous measurements combined (stat, statistical uncertainty; syst, systematic uncertainty; MeV, mega-electron volts; c, speed of light in a vacuum). This measurement is in significant tension with the standard model expectation.
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BACKGROUND: Tooth decay (caries) is a significant health burden in young children. There is strong evidence for the benefits of establishing appropriate home-based oral health behaviours in early childhood. Dental teams are well placed to provide this information and there is clear advice on what oral health information should be given to parents. However, research has shown that there is limited guidance, training and resources on how dental teams should deliver this advice. "Strong Teeth" is a complex oral health intervention, using evidence-based resources and training underpinned by behaviour change psychology, to support behaviour change conversations in dental practice. This early phase evaluation aims to assess the feasibility of this intervention, prior to a full-scale trial. METHODS: The study recruited 15 parents of children aged 0-2-years-old and 21 parents of children aged 3-5 years old, from five NHS dental practices across West Yorkshire. Participant demographics, self-reported brushing behaviours, dietary habits, a dental examination and three objective measures of toothbrushing were collected in a home-setting at baseline, then at 2-weeks and 2-months post-intervention. Recruitment, retention and intervention delivery were analysed as key process outcomes. Brushing habits were compared to national toothbrushing guidelines - the Delivering Better Oral Health toolkit (Public Health England). RESULTS: Strong Teeth was feasible to deliver in a General Dental Practice setting in 94% of cases. Feasibility of recruitment (37%) exceeded progression criterion, however retention of participants (75%) was below the progression criterion for the 0-2 age group. More than half of children recruited aged 3-5-years had caries experience (52%). Total compliance to toothbrushing guidance at baseline was low (28%) and increased after the intervention (52%), an improvement that was statistically significant. Dietary habits remained largely unchanged. Plaque scores significantly decreased in the 3-5-year-olds and toothbrushing duration increased in all age groups. CONCLUSION: "Strong Teeth" intervention delivery and data collection in the home setting was feasible. There was a positive indication of impact on reported toothbrushing behaviours. Some amendments to study design, particularly relating to the inclusion of the 0-2-year-old group, should be considered before progression to a full trial. Trial registration ISRCTN Register: ISRCTN10709150. Registered retrospectively 24/7/2019.
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Cárie Dentária , Saúde Bucal , Criança , Pré-Escolar , Cárie Dentária/prevenção & controle , Inglaterra , Estudos de Viabilidade , Humanos , Lactente , Recém-Nascido , Pais , Estudos Retrospectivos , Escovação DentáriaRESUMO
BACKGROUND AND OBJECTIVE: p53, an anti-tumour protein, is significantly inactivated in most tumours. A small molecule of nutlin-3a is used to activate its function by repressing (Mouse double minute 2 homolog) Mdm2 protein which inhibits its activity. In cancer patients, a high risk of drug-drug interactions (DDIs) is observed owing to their multi-dosing prescriptions, which may lead them to harmful effects. In the presented work, we have aimed to investigate the effect of pharmacodynamical interaction between two anti-cancer drugs, nutlin-3a and aspirin in the activation of p53 protein. METHODS: We have adapted control system techniques and designed a Proportional-Integral-Derivative (PID) controller. This controller is used to activate p53 protein. A drug interaction parameter is used to incorporate the effect of both drugs. Extensive simulation is performed using two different doses of aspirin, i.e. a low and a high dose of aspirin. RESULTS: The result shows no harmful effects of pharmacodynamical interaction when a low dose is administered along with nutlin-3a. When a high dose of aspirin is administered it acts as input disturbance and leads to undesirable over-expression of p53 protein. This can further harm other growth cells, thus inducing harmful effects. A comparative analysis is also tabulated with different dosing regimens which shows that a combination of nutlin-3a and a low dose of aspirin provides better results than a high dose of aspirin. CONCLUSION: Overall, the work provides an insight to the activation of p53 protein in cancer patients under the presence of pharmacodynamical interaction and might contribute to the effective management of cancer patients.
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Aspirina , Imidazóis , Piperazinas , Proteína Supressora de Tumor p53 , Apoptose , Aspirina/farmacologia , Linhagem Celular Tumoral , Humanos , Imidazóis/farmacologia , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-mdm2/metabolismoRESUMO
This paper reports the enhanced performance of cholesterol oxidase (COx) conjugated CdSe/ZnS quantum dots (QDs) by using water-soluble mercaptoacitic acid (MAA) as linker. The functionalized MAA-CdSe/ZnS QDs conjugated in four different dilutions of cholesterol oxidase significantly affected QDs photoluminescence intensities, which affected the process of charge transfer from QDs to MAA. The conjugation of COx to MAA-QDs in increased dilutions resulted in the regain of PL intensities, which were attributed to the passivation of MAA HOMO/LUMO states. The electrochemical impedance spectroscopy and cyclic voltammetry of the conjugated QDs were performed to get study the charge transfer mechanism. The 1:1000 diluted COx conjugated MAA-CdSe/ZnS QDs was found to have the lowest charge transfer resistance of 228 Ω, the highest diffusion (~ 1.39 × 10-13 cm2/s) and charge transfer rates (~ 4.5 × 10-6 s-1) between the electrode and the redox species. The current study demonstrated the sensitivity of electrochemical and optical based detection on the alkaline.
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Fungal infections in immune-compromised patients are an important cause of mortality and morbidity. Amphotericin B (Amp B) is considered a powerful fungicidal drug but its clinical usage has certain limitations when administered intravenously due to its toxicity and poor solubility. In consideration of such challenges, in cutaneous leishmaniasis, the topical application of Amp B can be a safer option in many aspects. Thus, herein, biopolymer of polycaprolactone (PCL) nanoparticles (NPs) were developed with the loading of Amp B by nanoprecipitation for the treatment of topical leishmanial infections. Various parameters, such as concentration of PCL and surfactant Poloxamer 407, were varied in order to optimize the formation of nanoparticles for the loading of Amp B. The optimized formulation exhibited a mean hydrodynamic particle size of 183 nm with a spherical morphology and an encapsulation efficiency of 85%. The applications of various kinetic models reveal that drug release from nanoformulation follows Korsmeyer-Peppas kinetics and has a high diffusion exponent at a physiological pH of 7.4 as well a skin relevant pH = 5.5. The activity of the prepared nanoparticles was also demonstrated in Leishmania infected macrophages. The measured IC50 of the prepared nanoparticle formulation was observed to be significantly lower when compared to control free Amp B and AmBisome® for both L. tropica KWH23 and L. donovani amastigotes in order to demonstrate maximum parasite inhibition. The prepared topical nanoformulations are capable of providing novel options for the treatment of leishmaniasis, which can be possible after in vivo assays as well as the establishment of safety profiles.
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Pertussis (or whooping cough) is a contagious disease mainly affecting infants and children and predominantly caused by Bordetella pertussis followed by Bordetella parapertussis. B. parapertussis causes a milder cough but usually symptomatically appears like B. pertussis infection. Thus the epidemiology of illness caused by B. parapertussis is not well understood. In this study, a sensitive and specific method for the rapid diagnosis of B. parapertussis is presented. The covalent immobilization of thiol-terminated DNA oligonucleotides (ss DNA SAM) on a silicon surface by disulfide bond formation is investigated with atomic force microscopy (AFM) and ellipsometry. The measurements indicated an average layer thickness of 5 ± 0.84 nm for 2 µg/µl concentration and 24 h incubation time. This thickness changed to 8.4 ± 0.92 nm for the same concentration (2 µg/µl) by altering the incubation time to 48 h. Ellipsometric data recorded before and after hybridization of B. parapertussis revealed an increase in mean grain area from 91 nm2 to 227 nm2 and a change in the refractive index from 1.489 to 1.648 for 2 µg/µl B. parapertussis, respectively. This change in the refractive index was used to evaluate the amount of adsorbed molecules and their density. The results showed that the density of adsorbed molecules increased from 0.2 to 0.97 g/cm3 after B. parapertussis attachment, respectively. To confirm the hybridization of B. parapertussis to ss DNA SAM, the ds DNA SAM was denatured and the ss DNA SAM surface was reproduced with an average height variation of 6.42 ± 0.75 nm. This showed the stability of the DNA film that can be tuned by varying the concentration and incubation time, thus providing a robust method for the label-free detection of B. parapertussis other than routinely used PCR detection.
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Técnicas Biossensoriais/métodos , Bordetella parapertussis/isolamento & purificação , DNA de Cadeia Simples/química , Adsorção , Ouro/química , Modelos Moleculares , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , Propriedades de Superfície , Fatores de TempoRESUMO
Esophageal perforation is an uncommon and challenging surgical emergency associated with high rates of morbidity and mortality. At present, no consensus exists on optimal management of the condition. The Pittsburgh Severity Score (PSS) is a tool intended to stratify perforation severity and guide treatment. However, there is a paucity of literature examining the validity of the score or its application in a UK population. This study aims to validate the PSS and explore its use in stratifying patients with esophageal perforation into distinct subgroups with differential outcomes in an independent UK study population.All patients treated for esophageal perforation at Queen Elizabeth Hospital, Birmingham between September 2003 and October 2017 were included in this study. Cases were identified using a combination of ICD-10 and OPCS informatics search codes and prospective case collection. Data relating to the clinical presentation, diagnosis, management, and outcome of cases were recorded using a preformed data collection form. PSS predictive performance was assessed against five outcomes: rates of post-perforation and post-operative complications, in-hospital mortality, length of intensive care (ICU/HDU) stay, and total length of hospital stay.A total of 87 cases were identified, consisting of 48 (55%) iatrogenic perforations, 24 (28%) cases of spontaneous (Boerhaave's) perforation, and 15 perforations due to other etiologies (17%). Operative management was favored in this series, with 47% of all perforations being treated surgically. Overall in-hospital mortality was 13%, coupled with a median length of hospital stay of 24 days (interquartile range [IQR]: 12-49), of which a median of 2 days was spent in intensive care facilities (IQR: 0-14). A total of 46% of patients developed post-perforation complications, with 59% of the operatively managed cohort developing complications post-operatively.The PSS was not found to be significantly predictive of post-perforation complications (area under the ROC curve [AUROC]: 0.62, p = 0.053) or in-hospital mortality (AUROC: 0.69, p = 0.057) for the cohort as a whole. However, a subgroup analysis found the accuracy of the PSS to vary considerably by etiology, being significantly predictive of post-perforation complications within the subgroup of Boerhaave's perforations (AUROC: 0.86, p = 0.004).In conclusion, we found that the PSS has some utility in stratifying esophageal perforation severity and predicting specific patient outcomes. However, it appears to be of more value when applied to the subgroup of patients with Boerhaave's perforations.
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Perfuração Esofágica/diagnóstico , Avaliação de Resultados da Assistência ao Paciente , Índice de Gravidade de Doença , Idoso , Perfuração Esofágica/mortalidade , Perfuração Esofágica/terapia , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos ProspectivosRESUMO
Pyrazinamide (PZA) is a key first-line antibiotic used for the short-course treatment of drug-sensitive and multidrug-resistant (MDR) isolates of tuberculosis. PZA exhibits potent action against semi-dormant bacilli in acidic environments. However, mutations that occur in target genes may cause technical difficulties in the diagnosis of PZA resistance during drug susceptibility testing. The objective of the current study is to identify mutations in pncAWT rpsA and rpsAWT panD genes among PZA-resistant isolates of Mycobacterium tuberculosis (MTB) circulating in the Pashtun dominant region, Khyber Pakhtunkhwa, Pakistan. We selected 18 PZA-resistant pncAWT strains from the Provincial Tuberculosis Reference Laboratory (PTRL) Khyber Pakhtunkhwa to investigate mutations in the coding region of rpsA and panD genes. The experiments were repeated for drug susceptibility testing using MGIT 960 automated system. In addition, eighteen PZA-resistant rpsA genes along with 5 susceptible strains and one H37Rv strain were sequenced. All 18 isolates were PZA-resistant. The majority of these isolates exhibited multidrug resistance (MDR) (13/18). We identified 14 non-synonymous and one synonymous mutation in the coding region of rpsA in 11 strains. All mutations were scattered throughout the gene and not reported previously. Further, we did not identify any mutation in 7 rpsAWT panD genes. Mutations in rpsA but not in panD occur in PZA-resistant pncAWT MTB isolates circulating in Khyber Pakhtunkhwa, Pakistan.
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Amidoidrolases/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Mutação , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Humanos , PaquistãoRESUMO
A search for the exotic meson X(5568) decaying into the B_{s}^{0}π^{±} final state is performed using data corresponding to 9.6 fb^{-1} from pp[over ¯] collisions at sqrt[s]=1960 GeV recorded by the Collider Detector at Fermilab. No evidence for this state is found and an upper limit of 6.7% at the 95% confidence level is set on the fraction of B_{s}^{0} produced through the X(5568)âB_{s}^{0}π^{±} process.
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The Physiologically based pharmacokinetic (PBPK) modeling is a supporting tool in drug discovery and improvement. Simulations produced by these models help to save time and aids in examining the effects of different variables on the pharmacokinetics of drugs. For this purpose, Sheila and Peters suggested a PBPK model capable of performing simulations to study a given drug absorption. There is a need to extend this model to the whole body entailing all another process like distribution, metabolism, and elimination, besides absorption. The aim of this scientific study is to hypothesize a WB-PBPK model through integrating absorption, distribution, metabolism, and elimination processes with the existing PBPK model.Absorption, distribution, metabolism, and elimination models are designed, integrated with PBPK model and validated. For validation purposes, clinical records of few drugs are collected from the literature. The developed WB-PBPK model is affirmed by comparing the simulations produced by the model against the searched clinical data. . It is proposed that the WB-PBPK model may be used in pharmaceutical industries to create of the pharmacokinetic profiles of drug candidates for better outcomes, as it is advance PBPK model and creates comprehensive PK profiles for drug ADME in concentration-time plots.
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Modelos Biológicos , Farmacocinética , Simulação por Computador , Coleta de Dados , Descoberta de Drogas/métodos , Descoberta de Drogas/normas , HumanosRESUMO
Background: Cervical cancer is the third most common cancer in women throughout the world. The human papillomavirus (HPV) E6 viral protein plays an essential role in proteasomal degradation of the cancer suppressant protein p53. As a result, p53 negative regulation and apoptosis relevant activities are abrogated, facilitating development of cervical cancer. Methods: A mathematical model of E6-p53 interactions was developed using mathematical laws. In-silico simulations were carried out on CellDesigner and as a test case the small molecule drug RITA was considered for its ability to rescue the functions of tumor suppressor p53 by inhibiting E6 mediated proteasomal degradation. Results: Using a computational model we scrutinized how p53 responds to RITA, and chemical reactions of this small molecule drug were incorporated to perceive the full effects. The evolved strategy allowed the p53 response and rescue of its tumor suppressor function to be delineated, RITA being found to block p53 interactions with E6 associated proteins. Conclusion: We could develop a model of E6-p53 interactions with incorporation of actions of the small molecule drug RITA. Suppression of E6 associated proteins by RITA induces accumulation of tumor suppressant p53. Using CellDesigner to encode the model ensured that it can be easily modified and extended as more data become available. This strategy should play an effective role in the development of therapies against cancer.
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Micro/nano electrodes employing nanotubes has attracted paramount attention in recent years due to their inherent superior mechanical and structural properties. Electrical interfaces with different geometries and sizes have been developed as electrodes for measuring action potentials and investigating neural information processing in neural networks. In this work, we investigated the possibility of using TiO2 nanotube arrays that were grown using electrochemical anodization technique, as a micro/nano electrode for neural interfacing. The morphology of fabricated nanotube arrays were found to be significantly affected by the applied voltage. Annealing and doping of TiO2 nanotube arrays has been performed to improve the structural and electrical properties of the nanotube arrays. It was found that the annealing and doping with nitrogen improve the electrical conductivity of the nanotube arrays. Moreover, the tube diameter and length can be controlled by changing the applied voltage and that can significantly affect the biocompatibility of the nanotube arrays. It was observed that nitrogen doped nanotubes with morphology consisting of 61nm diameter, 25nm wall thickness and tube length of 2.25µm could be good candidate to be used as electrodes for biological interfacing. This is due to the fact that the nitrogen doped nanotubes with aforementioned morphology possess great properties necessary for effective biological interfacing such as low impedance, high capacitance and good biocompatibility.
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Nanotubos , Técnicas Eletroquímicas , Eletrodos , TitânioRESUMO
We propose a new paradigm in the drug design for the revival of the p53 pathway in cancer cells. It is shown that the current strategy of using small molecule based Mdm2 inhibitors is not enough to adequately revive p53 in cancerous cells, especially when it comes to the extracting pulsating behavior of p53. This fact has come to notice when a novel method for the drug dosage design is introduced using system oriented concepts. As a test case, small molecule drug Mdm2 repressor Nutlin 3a is considered. The proposed method determines the dose of Nutlin to revive p53 pathway functionality. For this purpose, PBK dynamics of Nutlin have also been integrated with p53 pathway model. The p53 pathway is the focus of researchers for the last thirty years for its pivotal role as a frontline cancer suppressant protein due to its effect on cell cycle checkpoints and cell apoptosis in response to a DNA strand break. That is the reason for finding p53 being absent in more than 50% of tumor cancers. Various drugs have been proposed to revive p53 in cancer cells. Small molecule based drugs are at the foremost and are the subject of advanced clinical trials. The dosage design of these drugs is an important issue. We use control systems concepts to develop the drug dosage so that the cancer cells can be treated in appropriate time. We investigate by using a computational model how p53 protein responds to drug Nutlin 3a, an agent that interferes with the MDM2-mediated p53 regulation. The proposed integrated model describes in some detail the regulation network of p53 including the negative feedback loop mediated by MDM2 and the positive feedback loop mediated by Mdm2 mRNA as well as the reversible represses of MDM2 caused by Nutlin. The reported PBK dynamics of Nutlin 3a are also incorporated to see the full effect. It has been reported that p53 response to stresses in two ways. Either it has a sustained (constant) p53 response, or there are oscillations in p53 concentration. The claimed dosage strategy achieves the p53 response in the first case. However, for the induction of oscillations, it is shown through bifurcation analysis that to achieve oscillating behavior of p53 inhibition of Mdm2 is not enough, rather antirepression of the p53-Mdm2 complex is also needed which leads to the need of a new drug design paradigm.
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Desenho de Fármacos , Cálculos da Dosagem de Medicamento , Imidazóis/farmacologia , Piperazinas/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Biologia Computacional/métodos , Retroalimentação , Humanos , Imidazóis/uso terapêutico , Piperazinas/uso terapêutico , Ligação Proteica , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/agonistasRESUMO
@#BACKGROUND: We assessed whether the paediatric-appropriate facilities were available at Emergency Departments (ED) in community hospitals in a Canadian province. METHODS: We conducted a cross-sectional survey of EDs in community hospitals in Ontario, Canada that had inpatient paediatric facilities and a neonatal intensive care unit. Key informants were ED chiefs, clinical educators, or managers. The survey included questions about paediatric facilities related to environment, triage, training, and staff in EDs. RESULTS: Of 52 hospitals, 69% (n=36) responded to our survey. Of them, 14% EDs (n=5) had some separated spaces available for paediatric patients. About 53% (n=19) of EDs lacked children activities, e.g., toys. Only 11% (n=4) EDs were using paediatric triage scales and 42% (n=15) had a designated paediatric resuscitation bay. Only half of the ED (n=18) required from their staff to update paediatric life support training. Only 31% (n=11) had a designated liaison paediatrician for the ED. Paediatric social worker was present in only 8% (n=3) of EDs in community hospitals. CONCLUSION: Most of the Ontario community hospital EDs included in this survey had inadequate facilities for paediatric patients such as specific waiting and treatment areas.
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Extracellular data analysis has become a quintessential method for understanding the neurophysiological responses to stimuli. This demands stringent techniques owing to the complicated nature of the recording environment. In this paper, we highlight the challenges in extracellular multi-electrode recording and data analysis as well as the limitations pertaining to some of the currently employed methodologies. To address some of the challenges, we present a unified algorithm in the form of selective sorting. Selective sorting is modelled around hypothesized generative model, which addresses the natural phenomena of spikes triggered by an intricate neuronal population. The algorithm incorporates Cepstrum of Bispectrum, ad hoc clustering algorithms, wavelet transforms, least square and correlation concepts which strategically tailors a sequence to characterize and form distinctive clusters. Additionally, we demonstrate the influence of noise modelled wavelets to sort overlapping spikes. The algorithm is evaluated using both raw and synthesized data sets with different levels of complexity and the performances are tabulated for comparison using widely accepted qualitative and quantitative indicators.
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Nanotube structures have attracted tremendous attention in recent years in many applications. Among such nanotube structures, titania nanotubes (TiO2) have received paramount attention in the medical domain due to their unique properties, represented by high corrosion resistance, good mechanical properties, high specific surface area, as well as great cell proliferation, adhesion and mineralization. Although lot of research has been reported in developing optimized titanium nanotube structures for different medical applications, however there is a lack of unified literature source that could provide information about the key parameters and experimental conditions required to develop such optimized structure. This paper addresses this gap, by focussing on the fabrication of TiO2 nanotubes through anodization process on both pure titanium and titanium alloys substrates to exploit the biocompatibility and electrical conductivity aspects, critical factors for many medical applications from implants to in-vivo and in-vitro living cell studies. It is shown that the morphology of TiO2 directly impacts the biocompatibility aspects of the titanium in terms of cell proliferation, adhesion and mineralization. Similarly, TiO2 nanotube wall thickness of 30-40nm has shown to exhibit improved electrical behaviour, a critical factor in brain mapping and behaviour investigations if such nanotubes are employed as micro-nano-electrodes.
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Materiais Biocompatíveis , Nanotubos , Próteses e Implantes , Titânio , Osso e Ossos/cirurgia , Condutividade Elétrica , Eletrodos , Humanos , Dente/cirurgiaRESUMO
AIM: The burden of Type 2 diabetes is alarmingly high in South Asia, a region that has many genetically diverse ethnic populations. Genome-wide association studies (GWAS) conducted largely in European populations have identified a number of loci predisposing to Type 2 diabetes risk, however, the relevance of such genetic loci in many South Asian sub-ethnicities remains elusive. The aim of this study was to replicate 49 single nucleotide polymorphisms (SNPs) previously identified through GWAS in Punjabis living in Pakistan. METHODS: We examined the association of 49 SNPs in 853 Type 2 diabetes cases and 1945 controls using additive logistic regression models after adjusting for age and gender. RESULTS: Of the 49 SNPs investigated, eight showed a nominal association (P < 0.05) that also remained significant after controlling for the false discovery rate. The most significant association was found for rs7903146 at the TCF7L2 locus. For a per unit increase in the risk score comprising of all the 49 SNPs, the odds ratio in association with Type 2 diabetes risk was 1.16 (95% CI 1.13-1.19, P < 2.0E-16). CONCLUSION: These results suggest that some Type 2 diabetes susceptibility loci are shared between Europeans and Punjabis living in Pakistan.
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Povo Asiático/genética , Diabetes Mellitus Tipo 2/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Paquistão , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos TestesRESUMO
PURPOSE: To correlate the accuracy of intraoperative and surgical specimen (ex vivo) ultrasound (US) with pathological margin status at partial nephrectomy. MATERIALS AND METHODS: Patients undergoing partial nephrectomy for T1 renal tumours in the period May 2010-January 2014 at a single institution who had intraoperative specimen US were included. PN was performed by standardised technique with intraoperative tumour localisation. Following excision, surgical specimen (ex vivo) US was performed and the margin status was compared to the final histopathological analysis. The specificity of US to identify margin status was calculated as was the correlation between the ultrasonographic and final pathological margin. RESULTS: Forty-five patients were included (median age 61 years). Mean tumour size was 28.1 ± 10 mm, and 89 % were renal cell carcinomas with the remainder being oncocytomas. Forty-four cases had negative surgical margins on pathological analysis, and US had a specificity of 100 %. There was a strong correlation between the margin as measured on US and final analysis (Pearson's r = 0.86, p < 0.001). CONCLUSION: Results show that intraoperative, surgical specimen (ex vivo) US control of resection margins in patients undergoing PN is feasible and efficient. It represents a promising tool to ensure margin negativity during PN.
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Adenoma Oxífilo/diagnóstico por imagem , Adenoma Oxífilo/cirurgia , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Adenoma Oxífilo/patologia , Adulto , Idoso , Carcinoma de Células Renais/patologia , Feminino , Humanos , Cuidados Intraoperatórios , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Sensibilidade e Especificidade , UltrassonografiaRESUMO
OBJECTIVE: To compare the failure rates between Jet continuous positive airway pressure device (J-CPAP-variable flow) and Bubble continuous positive airway device (B-CPAP) in preterm infants with respiratory distress. STUDY DESIGN: Preterm newborns <34 weeks gestation with onset of respiratory distress within 6 h of life were randomized to receive J-CPAP (a variable flow device) or B-CPAP (continuous flow device). A standardized protocol was followed for titration, weaning and removal of CPAP. Pressure was monitored close to the nares in both the devices every 6 hours and settings were adjusted to provide desired CPAP. The primary outcome was CPAP failure rate within 72 h of life. Secondary outcomes were CPAP failure within 7 days of life, need for surfactant post-randomization, time to CPAP failure, duration of CPAP and complications of prematurity. An intention to treat analysis was done. RESULTS: One-hundred seventy neonates were randomized, 80 to J-CPAP and 90 to B-CPAP. CPAP failure rates within 72 h were similar in infants who received J-CPAP and in those who received B-CPAP (29 versus 21%; relative risks 1.4 (0.8 to 2.3), P=0.25). Mean (95% confidence intervals) time to CPAP failure was 59 h (54 to 64) in the Jet CPAP group in comparison with 65 h (62 to 68) in the Bubble CPAP group (log rank P=0.19). All other secondary outcomes were similar between the two groups. CONCLUSION: In preterm infants with respiratory distress starting within 6 h of life, CPAP failure rates were similar with Jet CPAP and Bubble CPAP.