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Tuberculosis (TB) is one of the top 10 leading causes of morbidity and mortality worldwide . In 2017, approximately 10 million people were infected with TB and 1.3 million patients faced mortality . Patients with active TB can infect up to 10–15 people over a year. There is a greater risk of transmission in overcrowded areas with limited air ventilation including large family units, prisons and slums [1, 2]. Without proper diagnosis and treatment, roughly 45% of non-HIV positive TB patients face mortality . With the help of global organizations and national TB treatment and control programmes, the global incidence of TB is declining by approximately 2% each year . The World Health Organization (WHO) TB-strategy aims to end the TB epidemic and encourages partners to fund national TB programmes to improve diagnosis and treatment of TB. The goal is to ultimately decrease death rates by 90% and decrease incidence rates by 80% . To achieve these goals, the decline in TB incidence needs to reach approximately 4–5% per year . The WHO 2018 TB report identified multidrug resistant TB (MDR-TB) as the leading factor hindering that goal . The incidence and spread of MDR-TB has drastically increased, where approximately 558 000 new cases of MDR-TB were diagnosed in 2017 causing more than 230 000 deaths globally . MDR-TB is identified by resistance to the two most powerful anti-TB treatment drugs including isoniazid and rifampicin . Patients with MDR-TB are required to start second-line anti-TB drugs (SLDs), which are limited, expensive, less effective and more toxic [1,2]. Therapy duration is one of the major limitations of second-line treatments, which may require up to two years of consistent use. Since TB affects mostly developing countries, long treatment durations and associated costs become a major challenge. In 2015, 15% of new TB cases were reported as MDR-TB, which drastically increased to 24% by 2017 . Even with significant improvements in molecular tests and diagnostic methods, MDR-TB is still on the rise where the success rate of treatments is between 50 and 60% . Additional characteristics including socioeconomic and sociocultural factors need to be considered when targeting and treating patients with MDR-TB.
Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
Cholera is an important public health problem in Bangladesh. Interventions to prevent cholera depend on their cost-effectiveness which in turn depends on cholera incidence. Hospital-based diarrhoeal disease surveillance has been ongoing in six Bangladeshi hospitals where a systematic proportion of patients admitted with diarrhoea were enrolled and tested for Vibrio cholerae. However, incidence calculation using only hospital data underestimates the real disease burden because many ill persons seek treatment elsewhere. We conducted a healthcare utilization survey in the catchment areas of surveillance hospitals to estimate the proportion of severe diarrhoeal cases that were admitted to surveillance hospitals and estimated the population-based incidence of severe diarrhoea due to V. cholerae by combining both hospital surveillance and catchment area survey data. The estimated incidence of severe diarrhoea due to cholera ranged from 0·3 to 4·9/1000 population in the catchment area of surveillance hospitals. In children aged <5 years, incidence ranged from 1·0 to 11·0/1000 children. Diarrhoeal deaths were most common in the Chhatak Hospital's catchment area (18·5/100 000 population). This study provides a credible estimate of the incidence of severe diarrhoea due to cholera in Bangladesh, which can be used to assess the cost-effectiveness of cholera prevention activities.
The world poultry industry is under great stress due to parasitic diseases; coccidiosis being one which is responsible for substantial economic losses worldwide. In 1948 the first research paper was published about the treatment of coccidiosis with sulphaquinoxaline. After six decades, researcher's attention has focused on DNA vaccination, especially as certain anticoccidials have failed due to drug resistance and residues. Thus far vaccination is partially successful but is accompanied by disadvantages: e.g. instability, inferiority control, cost-effectiveness, and inefficiency in opposition to a large number of coccidian strains which are prevalent in different geographical areas. Due to developments whereby genetically engineered DNA can be administered in vaccine form to provoke cellular and humoral immune responses; there has been huge development in the practical application of this field. In the last decade a number of DNA vaccines employing different strategies have been tested to produce appropriate immune responses against coccidiosis. The DNA fragments taken from all the four important species, E. tenella, E. necatrix, E. maxima and E. acervulina were able to provoke appropriate immune responses against challenging infections with homologous species; however, most of them were not able to provoke a response with heterologous infection. The shared DNA antigen in two different species of Eimeria; E. tenella and E. acervulina was able to produce sufficient immune responses, not only against these species but also against E. necatrix, but not against E. maxima. E. maximum is the biggest and most complex of all the seven species and it has come ahead as a challenge for DNA vaccine researchers.
Ketamine produces rapid antidepressant effects in treatment-resistant depression (TRD), but the magnitude of response varies considerably between individual patients. Brain-derived neurotrophic factor (BDNF) has been investigated as a biomarker of treatment response in depression and has been implicated in the mechanism of action of ketamine. We evaluated plasma BDNF and associations with symptoms in 22 patients with TRD enrolled in a randomized controlled trial of ketamine compared to an anaesthetic control (midazolam). Ketamine significantly increased plasma BDNF levels in responders compared to non-responders 240 min post-infusion, and Montgomery–Åsberg Depression Rating Scale (MADRS) scores were negatively correlated with BDNF (r=−0.701, p = 0.008). Plasma BDNF levels at 240 min post-infusion were highly negatively associated with MADRS scores at 240 min (r = −0.897, p=.002), 24 h (r = −0.791, p = 0.038), 48 h (r = −0.944, p = 0.001) and 72 h (r = −0.977, p = 0.010). No associations with BDNF were found for patients receiving midazolam. These data support plasma BDNF as a peripheral biomarker relevant to ketamine antidepressant response.
During epidemics of cholera in two rural sites (Bakerganj and Mathbaria), a much higher proportion of patients came for treatment with severe dehydration than was seen in previous years. V. cholerae O1 isolated from these patients was found to be El Tor in its phenotype, but its cholera toxin (CT) was determined to be that of classical biotype. Whether the observed higher proportion of severe dehydration produced by the El Tor biotype was due to a shift from El Tor to classical CT or due to other factors is not clear. However, if cholera due to strains with increased severity spread to other areas where treatment facilities are limited, there are likely to be many more cholera deaths.
The coherent structure in the near-field of an axisymmetric turbulent jet at a Reynolds number of 3.8 × 105 and Mach number of 0.3 is experimentally characterized by a vector implementation of the proper orthogonal decomposition (POD). The POD eigenfunctions and associated eigenvalues are extracted at several selected streamwise locations in the initial region. The focus on the near-field is motivated by its importance in numerous technical applications. Results show a rapid energy convergence with POD mode number. Examination of the relative energy contained in the combined azimuthal and radial components of the POD modes reveals that it is comparable to that in the streamwise component. The streamwise evolution of the eigenvalue spectra is characterized by a remarkable variation in the azimuthal mode number energy distribution, leading to the dominance of azimuthal mode m = 1 beyond the end of the jet core. In contrast, a scalar implementation using only the streamwise component shows the dominance of mode m = 2 which is consistent with previous scalar implementations of the POD. For a given azimuthal mode number, the eigenvalue spectra exhibit a broad peak which occurs at a constant value of Strouhal number based on local shear layer momentum thickness and local jet maximum velocity. The phase information required for a local reconstruction of the jet structure is obtained by projecting the POD eigenmodes onto instantaneous realizations of the flow at fixed streamwise locations. The instantaneous realizations are obtained by utilizing cross-stream arrays of multi-sensor probes in conjunction with linear stochastic estimation (LSE). Results clearly show the local dynamic behaviour of each component of the jet structure.
The terms ‘conversion’, ‘hysteria’ and ‘conversion hysteria’ were used interchangeably to describe a condition characterised by a single somatised symptom, often pseudo-neurological in nature. DSM–III (American Psychiatric Association, 1980) expanded the concept of conversion to generalised symptoms involving loss or alteration of physical functioning suggestive of a physical disorder, along with a clinical indication that the conversion was an expression of psychological conflict or need. The type of symptom or deficit should be specified as: with motor symptom or deficit, with sensory symptom or deficit, with seizure or convulsions, or with mixed presentation (Kaplan & Sadock, 2004).
To determine whether hepatitis B virus (HBV) transmission occurred among patients visiting a physician's office and to evaluate potential transmission mechanisms.
Serologic survey, retrospective cohort study, and observation of infection control practices.
Private medical office.
Those visiting the office between March 1 and December 26, 2001.
We identified 38 patients with acute HBV infection occurring between February 2000 and February 2002. The cohort study, limited to the 10 months before outbreak detection, included 91 patients with serologic test results and available charts representing 18 case-patients and 73 susceptible patients. Overall, 67 patients (74%) received at least one injection during the observation period. Case-patients received a median of 14 injections (range, 2-25) versus 2 injections (range, 0-17) for susceptible patients (P < .001). Acute infections occurred among 18 (27%) of 67 who received at least one injection versus none of 24 who received no injections (RR, 13.6; CI95, 2.4-undefined). Risk of infection increased 5.2-fold (CI95, 0.6-47.3) for those with 3 to 6 injections and 20.0-fold (CI95, 2.8-143.5) for those with more than 6 injections. Typically, injections consisted of doses of atropine, dexamethasone, vitamin B12, or a combination of these mixed in one syringe. HBV DNA genetic sequences of 24 patients with acute infection and 4 patients with chronic infection were identical in the 1,500-bp region examined. Medical staff were seronegative for HBV infection markers. The same surface was used for storing multidose vials, preparing injections, and dismantling used injection equipment.
Administration of unnecessary injections combined with failure to separate clean from contaminated areas and follow safe injection practices likely resulted in patient-to-patient HBV transmission in a private physician's office.
We show a direct impact of El Niño/Southern Oscillation (ENSO) related fires on the demography and persistence of the siamang (Symphalangus syndactylus), a frugivorous, Southeast Asian rainforest primate. Siamang groups affected by ENSO-related wildfires in a Sumatran rainforest were significantly smaller and experienced significantly lower infant and juvenile survival. Likelihood of infants surviving to subadults was higher by a factor of 2.8 for groups in undisturbed habitat. Burn groups had access to 48% fewer reproductive-size strangling fig trees in their territories, compared to non-burn groups. Dietary and foraging behaviour changes associated with habitat disturbance may result in lower productivity and higher mortality of young animals. Reproductive potential of burn groups is insufficient to offset low survival and groups are unlikely to persist for more than two generations. Increasing frequency of ENSO events increases the likelihood that siamang and other long-lived species that rely on fruiting trees will experience multiple fires within one generation; the resulting reduction in seed dispersal services will slow recovery of burned forest.
Crosses between certain genotypes of common bean result in dwarfing of F1 plants and lethal dwarfing in a
proportion of the F2 population. This is under the control of the semi-dominant alleles, DL1 and DL2 at two
complementary loci which are expressed in the root and shoot respectively. The various DL genotypes can be
simulated by grafting. The graft combination DL1DL1dl2dl2/dl1dl1DL2DL2 was found to have a significantly
higher root dry matter fraction than either parent. Lethally dwarfed plants (DL1DL1DL2DL2) and the analogous
lethal graft combination (dl1dl1DL2DL2/DL1DL1dl2dl2) exhibit failure of root growth and have very low root
fractions. Hybrids or graft combinations with failed roots ceased growth and accumulated large amounts of starch
throughout their hypocotyls. In sterile culture, both lethal dwarfs and lethal graft combinations were able to grow
roots if sucrose was added to the growth medium. This indicates that a failure of sucrose translocation to the roots
is probably responsible for failed root growth. Data from screening the DL genotypes of 49 cultivars could be fully
explained using the DL system hypothesis, and grafting proved to be efficient for identifying DL genotype. The
DL system might be of fundamental importance in root–shoot partitioning. Current evidence favours the
hypothesis that failure of root growth is the outcome of excessively high sink strength of shoots compared to roots,
which might arise from signalling incompatibilities between the genotypes.
The solid state luminescent properties of new statistical copolymers of 2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylene vinylene and a porphyrin-substituted phenylene vinylene are reported. The photoluminescence, PL, emission shows an efficient energy transfer to the porphyrin, in spite of the small absorption coefficient of the porphyrin in the wavelength range of the poly [2-methoxy-5-(2'- ethylhexyloxy)-1,4-phenylene vinylene], MEH-PPV, emission. At a porphyrin content of 0.25%, by weight, the emission is already dominated by the porphyrin. The PL efficiency of these copolymers is significantly reduced from the value of 13% for MEH-PPV down to 3% for the copolymer with 10.84% of porphyrin. Efficient energy transfer is also observed in the emission spectra of light-emitting diodes.
Biosensors are a special class of chemical sensors that take advantage of the high selectivity and sensitivity of biologically active material. We are currently investigating the characteristics of various deposited electrode coatings (Au and Pt) on 10 MHz quartz crystals using the sputtering method. We are also investigating the effect of magnetic behavior (by intermixing Fe and Ni with electrodes) on the binding nature of antigen with the substrate. A change in mass occurs due to the binding of antigens and antibodies on the surface of the thin film coating. The frequency change as a result of a change in mass makes it possible to use these crystals as biological sensor devices. This paper describes the construction of antibody-based piezoelectric crystals capable of detecting mycobacterial antigens in diluted cultures of attenuated M. tuberculosis. The microstructural features of these crystals have been studied using scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques. The crystallographic properties have been characterized using the X-ray diffraction (XRD) method. The long term objective of this research is to develop a rapid quantitative method of analysis for the diagnosis of tuberculosis (TB) and other infections caused by mycobacteria, using biosensor technology.
The oxygen-deficient orthorhombic oxide YBa2Cu3O7-δ has been the center of intense recent interest because of its high Tc superconducting proper-ties[l-3]. Recently, the structurally related La3Ba3Cu3O15-δ, has received increasing attention[4–9]. The pure Y analog[10,11] cannot be synthesized by usual solid state reaction routes probably because of its metastability near 880°C. Here we report on the successful synthesis of pure tetragonal Y3,Ba3CU6O15-δ (referred to as Y 3–3–6), via the firing of an atomically mixed citrate precursor at a relatively low temperature. X-ray diffraction data characterize Y 3–3–6 to be isostructural with the corresponding La compound. The unit cell composition can then be written as: Y(Ba2−x Yx) CU3O7+δ with the parent compound at x = 0.50. Specimens of Y 3–3–6 at × = 0.50 and 0.375 annealed at 650°C under 1 atmosphere of O2 are non-superconducting. Higher pressure O2 annealing and fluorine-doping leads to a 1–5% superconducting volume fraction with onset at 85K. Annealing near 880°C creates a 10% superconducting fraction which shows near-zero resistivity at 62K and a reproducible, small resistive transition near 260K.
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