Stochastic simulation of successive waves of COVID-19 in the province of Barcelona.

Analytic compartmental models are currently used in mathematical epidemiology to forecast the COVID-19 pandemic evolution and explore the impact of mitigation strategies. In general, such models treat the population as a single entity, losing the social, cultural and economical specificities. We present a network model that uses socio-demographic datasets with the highest available granularity to predict the spread of COVID-19 in the province of Barcelona. The model is flexible enough to incorporate the effect of containment policies, such as lockdowns or the use of protective masks, and can be easily adapted to future epidemics. We follow a stochastic approach that combines a compartmental model with detailed individual microdata from the population census, including social determinants and age-dependent strata, and time-dependent mobility information. We show that our model reproduces the dynamical features of the disease across two waves and demonstrates its capability to become a powerful tool for simulating epidemic events.

Online adaptive MR-guided radiotherapy for rectal cancer; feasibility of the workflow on a 1.5T MR-linac: clinical implementation and initial experience.

BACKGROUND AND PURPOSE: Daily online adaptation of the clinical target volume (CTV) using MR-guided radiotherapy enables margin reduction of the planning target volume (PTV). This study describes the implementation and initial experience of MR-guided radiotherapy on the 1.5T MR-linac and evaluates treatment time, patient compliance, and target coverage, including an initial assessment of margin reduction. MATERIALS AND METHODS: Patients were treated on a 1.5T MR-linac (7MV, FFF). At each fraction a 3D T2 weighted (T2w) MR-sequence was acquired on which the CTV was adapted after a deformable registration of the contours from the pre-planning CT scan. Based on the new contours a full online replanning was done after which a new 3D T2w MR-sequence was acquired for position verification. A 5 field Intensity Modulated Radiotherapy (IMRT) plan was delivered. RESULTS: Forty-three patients with rectal cancer were treated with 25 Gy in 5 fractions of which 18 with reduced margins. In total, 204 of 215 fractions were delivered on the MR-linac all of which obtained a clinically acceptable treatment plan. Median in-room time per fraction was 48 min (interquartile range 8). No fractions were canceled or interrupted because of patient intolerance. CTV coverage after margin reduction was good on all post-treatment scans but one due to passing gas. CONCLUSION: MR-guided radiotherapy using daily full online recontouring and replanning on a 1.5T MR-linac for rectal cancer is feasible and currently takes about 48 min per fraction.

Conductive Atomic Force Microscope Study of Bipolar and Threshold Resistive Switching in 2D Hexagonal Boron Nitride Films.

This study investigates the resistive switching characteristics and underlying mechanism in 2D layered hexagonal boron nitride (h-BN) dielectric films using conductive atomic force microscopy. A combination of bipolar and threshold resistive switching is observed consistently on multi-layer h-BN/Cu stacks in the low power regime with current compliance (I comp ) of less than 100 nA. Standard random telegraph noise signatures were observed in the low resistance state (LRS), similar to the trends in oxygen vacancy-based RRAM devices. While h-BN appears to be a good candidate in terms of switching performance and endurance, it performs poorly in terms of retention lifetime due to the self-recovery of LRS state (similar to recovery of soft breakdown in oxide-based dielectrics) that is consistently observed at all locations without requiring any change in the voltage polarity for I comp ~1-100 nA.

Intrinsic Resistance Switching in Amorphous Silicon Suboxides: The Role of Columnar Microstructure.

We studied intrinsic resistance switching behaviour in sputter-deposited amorphous silicon suboxide (a-SiO x ) films with varying degrees of roughness at the oxide-electrode interface. By combining electrical probing measurements, atomic force microscopy (AFM), and scanning transmission electron microscopy (STEM), we observe that devices with rougher oxide-electrode interfaces exhibit lower electroforming voltages and more reliable switching behaviour. We show that rougher interfaces are consistent with enhanced columnar microstructure in the oxide layer. Our results suggest that columnar microstructure in the oxide will be a key factor to consider for the optimization of future SiOx-based resistance random access memory.

Assessment of the variability in the dimensions of the intact pelvic canal in South Africans: A pilot study.

Cephalopelvic disproportion is common among Africans and is a major cause of maternal and perinatal mortality and morbidity. As the dimensions of the pelvis may vary between populations and according to stature and age, they need to be considered during childbirth and also in the planning and performance of pelvic and perineal procedures. The aim of this study was to assess the possible variations in the dimensions of the intact pelvic canal in South Africans and their implications. Eighty intact cadaver pelves, belonging to 40 white South Africans (20 males and 20 females) and 40 black South Africans (20 males and 20 females) were used for both metric and geometric morphometric analyses. Pelvic inlet shapes did not differ significantly between groups but pelvic inlet and midpelvic dimensions were the greatest in white South Africans and females. The pubic symphyseal length was the greatest in white males and the smallest in black females, resulting in a smaller pelvic cavity anteriorly than for white females. Pelvic outlet shapes varied significantly between sexes in white South Africans and between white and black males. Females presented with the greatest dimensions. Black South African females presented with an elongated anteroposterior outlet diameter. Certain transverse pelvic diameters correlated positively with age in white males and with height in females. In planning childbirth options, the smaller pelvic inlet of black females and stature-dependent diameters should be considered. Pelvic and perineal surgery may be technically more challenging because of smaller pelvic dimensions in black South Africans, especially in males.

Degenerative trends of the palmaris longus muscle in a South African population.

The literature reports that the palmaris longus muscle (PL) is only found in mammals in which the forelimbs are weight-bearing extremities. It is suggested that the function of this muscle has been taken over by the other flexors in the forearm. Terms used in the literature to describe the diminishing of this muscle include retrogressive or phylogenetic degenerative trends. The aims of this study were to determine the prevalence of PL in a South African population and whether a phylogenetic degenerative trend for the PL exists. To determine the prevalence of the PL, five groups, representing different age intervals (Years 0-20, 21-40, 41-60, 61-80, and 81-99) were used. A sample of 706 participants of various ages was randomly selected. Statistical analysis included comparisons of the prevalence of the muscle between males and females and left and right sides, using a student t-test. A Chi-squared test was used to determine a possible phylogenetic degenerative trend of PL within the five groups. The sample yielded a bilateral absence of the PL in 11.9% of the cases. The muscle was unilaterally absent on the left side in 7.65% and 6.94% on the right side. The Chi-squared tests revealed a P-value of 0.27 for the left arm and 0.39 for the right arm. No obvious trend could be established for the phylogenetic degeneration of the PL in this study. It would appear that the PL muscle should not be considered as a phylogenetically degenerating muscle in a South African population.

The value of Tuffier's line for neonatal neuraxial procedures.

The spine of L4 usually lies on a line drawn between the highest points of the iliac crests (Tuffier's line) in adults. Although its accuracy has been questioned, it is still commonly used to identify the spinous process of the 4th lumbar vertebra before performing lumbar neuraxial procedures. In children, this line is said to cross the midline at the level of L5. A literature search revealed that the description this surface anatomical line is vague in neonates. The aims of this study were to determine the vertebral level of Tuffier's line, as well as its distance from the apex of the sacrococcygeal membrane (ASM), in 39 neonatal cadavers in both a prone and flexed position. It was found that when flexed, Tuffier's line shifted from the level of L4/L5 (prone position) to the upper third of L5. The mean distance from the ASM to Tuffier's line was 23.64mm when prone and 25.47 mm when flexed, constituting a statistically significant increase in the distance (P=0.0061). Therefore, in the absence of advanced imaging modalities, Tuffier's line provides practitioners with a simple method of determining a level caudal to the termination of the spinal cord, at approximately the L4/L5 in a prone neonate and the upper margins of L5 when flexed.

The utilization of red cell concentrates at Kimberley Hospital Complex, Northern Cape Province, South Africa.

This prospective clinical audit of the utilization of red cell concentrates assesses 55 consecutive transfusion episodes in chronically anaemic adult patients. It examines the appropriateness and outcome of the transfusion episodes; over-transfusion and wastage rates, assessment of anaemia, the informed consent process, and if teaching influenced these parameters when compared to an earlier retrospective audit. The audit revealed several strengths and weaknesses relating to our institution's transfusion practices. Training sessions led to clinically and economically important improvements in transfusion decisions, the investigation of anaemia and the obtainment of informed consent prior to transfusions.

The diagnostic performance of the GenoType MTBDRplus version 2 line probe assay is equivalent to that of the Xpert MTB/RIF assay.

Molecular diagnostics for Mycobacterium tuberculosis have recently been endorsed by the World Health Organization. The Xpert MTB/RIF assay was endorsed for use on patient material, regardless of smear gradation, while the GenoType MTBDRplus (version 1) has been limited for use on smear-positive patient material. In this study, we evaluated the diagnostic performance of the Xpert MTB/RIF and GenoType MTBDRplus (version 2) assays on smear-positive and smear-negative patient specimens submitted to a high-throughput diagnostic laboratory. A total of 282 consecutive specimens were subjected to the two new molecular assays, and their performance characteristics were assessed relative to the routine diagnostic standard. Both assays showed similar diagnostic performance characteristics. The sensitivities of the GenoType MTBDRplus (v2.0) and Xpert MTB/RIF assays for the detection of culture-positive M. tuberculosis were 73.1% and 71.2%, respectively, while the specificities of both assays were 100%. Both assays were able to diagnose the presence of M. tuberculosis in 57 to 58% of smear-negative cases, suggesting that the performance characteristics were dependent on bacillary load. The detection of M. tuberculosis in culture-negative specimens confirmed that molecular assays should not be used for treatment monitoring. The sensitivity and specificity for rifampin resistance detection were 100% in both assays; however, the GenoType MTBDRplus (v2.0) assay provided additional information on isoniazid susceptibility. The GenoType MTBDRplus (v2.0) assay will complement the Xpert MTB/RIF screening assay by validating rifampin susceptibility and providing information on isoniazid susceptibility. In addition, the GenoType MTBDRplus (v2.0) assay will provide pharmacogenetic information that may be critical in guiding appropriate treatment.

Mycobacterium tuberculosis population structure determines the outcome of genetics-based second-line drug resistance testing.

The global emergence of multidrug-resistant tuberculosis has highlighted the need for the development of rapid tests to identify resistance to second-line antituberculosis drugs. Resistance to fluoroquinolones and aminoglycosides develops through nonsynonymous single nucleotide polymorphisms in the gyrA and gyrB genes and the rrs gene, respectively. Using DNA sequencing as the gold standard for the detection of mutations conferring resistance, in conjunction with spoligotyping, we demonstrated heteroresistance in 25% and 16.3% of Mycobacterium tuberculosis isolates resistant to ofloxacin and amikacin, respectively. Characterization of follow-up isolates from the same patients showed that the population structure of clones may change during treatment, suggesting different phases in the emergence of resistance. The presence of underlying mutant clones was identified in isolates which failed to show a correlation between phenotypic resistance and mutation in the gyrA or rrs gene. These clones harbored previously described mutations in either the gyrA or rrs gene, suggesting that rare mutations conferring resistance to ofloxacin or amikacin may not be as important as was previously thought. We concluded that the absence of a correlation between genotypic and phenotypic resistance implies an early phase in the emergence of resistance within the patient. Thus, the diagnostic utility of genetics-based drug susceptibility tests will depend on the proportion of patients whose bacilli are in the process of acquiring resistance in the study setting. These data have implications for the interpretation of molecular and microbiological diagnostic tests for patients with drug-susceptible and drug-resistant tuberculosis who fail to respond to treatment and for those with discordant results.

inhA promoter mutations: a gateway to extensively drug-resistant tuberculosis in South Africa?

SETTING: Western Cape and Eastern Cape Provinces, South Africa. OBJECTIVE: To assess the potential association between the evolution of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis and mutations in the inhA promoter or the katG gene. DESIGN: Analysis of the frequency distribution of isoniazid (INH) resistance conferring mutations in a population sample of drug-resistant isolates of M. tuberculosis. RESULTS: In the Western Cape and Eastern Cape Provinces, the percentage of isolates exhibiting inhA promoter mutations increased significantly from respectively 48.4% and 62.4% in multidrug-resistant tuberculosis (MDR-TB) isolates to 85.5% and 91.9% in XDR isolates. Data from the Western Cape revealed that significantly more XDR-TB isolates showed mutations in the inhA promoter than in katG (85.5% vs. 60.9%, P < 0.01), while the respective proportions were equal for INH-resistant non-MDR-TB isolates (∼30%). CONCLUSIONS: inhA promoter mutations are strongly associated with XDR-TB in South Africa. We suggest that this is due to the dual resistance to ethionamide and (low-dose) INH conferred by inhA promoter mutations. The use of molecular probe assays such as the GenoType® MTBDRplus assay, which allows the detection of inhA promoter mutations, could enable treatment regimens to be adjusted depending on the pharmacogenetic properties of the mutations detected.

Preliminary results on a study to locate the pterygopalatine fossa using mathematical formulae.

Blocking the contents of the pterygopalatine fossa (PPF) has been shown to be effective in treating most orofacial pain including that associated with trigeminal neuralgia. However, the technique is not widely used, and we propose it to be due to the vague descriptions of the techniques in the literature. The aim of this study was therefore to achieve an alternative method of locating the PPF. One hundred and sixty skulls from the department of Anatomy, University of Pretoria, were used. Distinct landmarks (both anthropometric and clinical) accompanied by existing and new anthropometric measurements were used to define the location of the PPF. Regression analysis was used to measure the reliability of predicting the location of the PPF. From the results, two mathematical formulae were devised (one for each side). These formulae were tested on 47 cadavers by inserting a needle at the calculated points after which the areas where dissected to determine whether or not the needle had entered the PPF. Our results showed an accuracy of 65.2% on the right and 54.4% on the left. In conclusion, improvement in the accuracy of the technique could aid in the management of various pain disorders as well as pain management during surgery.

The anatomical basis of venographic filling defects of the transverse sinus.

Obstruction of the intracranial dural venous sinuses would result in an increase in intracranial dural venous pressure. This intracranial hypertension is not only the result of poor cerebral venous drainage but also life threatening. The aim of this study was to identify the structures, which may show signs of potential venographic filling defect qualities, including trabeculae/septa (also described as "fibrous bands") and arachnoid granulations, which ultimately can lead to increased intracranial dural sinus venous pressure. A total of 102 cadavers and living patients were used for the study. Fifty-three percent of the subjects presented with structures in their transverse sinuses that could be potential venous filling defects. Thirty percent of the subjects presented with arachnoid granulations in the right transverse sinus, which were found to be significantly dominant (Chi-square; p < 0.05). The study also revealed the presence of 1 to 5 septa in 29.4% of the subjects. The septa were found to be more dominant in the central (30%) and lateral (22%) thirds of the right transverse sinuses, while the central third of the left transverse sinus proved to be the least dominant occurring site (8%). In general, the right transverse sinus is highly more significantly dominant in septal occurrence (Chi-square; p < 0.01) than the left transverse sinus. We conclude from the statistical evidence that the right transverse sinus demonstrates significantly more potential venographic filling defects than the left sinus and submit that this information may assist in management options for patients diagnosed with idiopathic intracranial hypertension as well as direct future research.

Drug-resistant tuberculosis epidemic in the Western Cape driven by a virulent Beijing genotype strain.

Temporal analysis of drug-resistant tuberculosis (TB) cases in the Western Cape, South Africa, showed a 1.5-fold increase over a 2-year period, suggesting a doubling time of 8.2 years. This increase was strongly associated with multidrug resistance and the Beijing genotype. Forty-two per cent of the overall increase was due to the Beijing genotype strain R220, suggesting that this strain had evolved unique properties that allowed for both acquisition and transmission of drug resistance. To curb the drug-resistant TB epidemic in this setting, it will be essential to implement rapid diagnostics and efficient infection control measures, improve contact screening and ensure treatment adherence.

Initial default from tuberculosis treatment: how often does it happen and what are the reasons?

A study in 11 primary health care facilities in and around Cape Town determined the proportion of bacteriologically confirmed tuberculosis (TB) cases who did not start treatment (initial default) and identified reasons for it. Databases from centralised laboratories were compared with electronic TB treatment registers. Fourteen per cent (373/2758) of TB suspects were TB cases. Of the 58 (16%) initial defaulters, 14 (24%) died, while 26 (45%) could not be interviewed for address-related reasons. The 18 subjects who were interviewed indicated reasons for initial default that were (56%) or were not (44%) directly linked to services. High initial default rates require improvement in the quality of health services.

Two-dimensional mapping of chemical information at atomic resolution.

The simultaneous measurement of structural and chemical information at the atomic scale provides fundamental insights into the connection between form and function in materials science and nanotechnology. We demonstrate structural and chemical mapping in Bi(0.5) Sr(0.5) MnO3 using an aberration-corrected scanning transmission electron microscope. Two-dimensional mapping is made possible by an adapted method for fast acquisition of electron energy-loss spectra. The experimental data are supported by simulations, which help to explain the less intuitive features.

New developments in electron energy loss spectroscopy.

In the electron microscope, spectroscopic signals such as the characteristic X-rays or the energy loss of the incident beam can provide an analysis of the local composition or electronic structure. Recent improvements in the energy resolution and sensitivity of electron spectrometers have improved the quality of spectra that can be obtained. Concurrently, the calculations used to simulate and interpret spectra have made major advances. These developments will be briefly reviewed. In recent years, the focus of analytical electron microscopy has moved away from single spectrum acquisition to mapping and imaging. In particular, the use of spectrum imaging (SI), where a full spectrum is acquired and stored at each pixel in the image is becoming widespread. A challenge for the application of spectrum imaging is the processing of such large datasets in order to extract the significant information. When we go beyond the mapping of composition and look to map bonding and electronic structure this becomes both more important and more difficult. Approaches to processing spectrum imaging data sets acquired using electron energy loss spectroscopy (EELS) will be explored in this paper.

Spread of an emerging Mycobacterium tuberculosis drug-resistant strain in the western Cape of South Africa.

BACKGROUND: South Africa has a high burden of drug-resistant tuberculosis (TB). METHODS: Routine drug susceptibility testing was performed prospectively over a 2-year period on Mycobacterium tuberculosis isolates in two health districts of the Western Province, South Africa. A cluster of drug-resistant strains that shared a rare mutation in katG315 was found in 64 of the 450 cases identified as having been infected with drug-resistant TB. Isolates belonging to this cluster were phenotypically and genotypically characterised. Epidemiological and clinical characteristics were used to identify mechanisms leading to the acquisition and spread of this drug-resistant strain. RESULTS: An outbreak of an emerging non-Beijing drug-resistant strain infecting 64 pulmonary tuberculosis (PTB) cases was identified. This previously undetected genotype (now designated DRF150) is characterised by five IS6110 insertions, specific spoligotypes and high levels of resistance to the first-line TB medications isoniazid, streptomycin and rifampicin. In 45% of the cases it is also resistant to ethambutol and pyrazinamide. Key factors leading to the development and spread of this drug-resistant genotype were inappropriate chemotherapy, poor adherence to treatment and prolonged periods of infectiousness due to delays in susceptibility testing. CONCLUSIONS: Molecular markers allowed early identification of an emerging non-Beijing drug-resistant strain.

Tuberculosis epidemiology in six provinces of Vietnam after the introduction of the DOTS strategy.

SETTING: Six provinces in Vietnam where the DOTS strategy was introduced in 1989. OBJECTIVE: To assess the impact of improved tuberculosis (TB) control on TB epidemiology in Vietnam. METHODS: Data from the surveillance system in the period 1990-2003 were analysed to assess trends of notification rates and the mean ages of notified cases. Data from repeated tuberculin surveys in the period 1986-2002 were estimated to assess the prevalence of TB infection, the annual risk of infection and its trend using various cut-off points in those with and without bacille Calmette-Guérin (BCG) scar. RESULTS: Age-standardised notification rates in the period 1996-2003 declined significantly, by 2.6% to 5.9% per year, in five provinces. However, in four provinces notification rates in the age group 15-24 years increased significantly, by 4.5% to 13.6% per year, during this period. The mean age of newly diagnosed patients with smear-positive TB increased up to 1995 but decreased thereafter. The annual risk of TB infection showed a significant annual decrease (4.9% per year) in one province in surveys performed between 1986 and 1997, and in two provinces (6.6% and 4.7%) in surveys conducted between 1993 and 2002. CONCLUSION: These data suggest limited impact to date of the DOTS strategy in Vietnam.

Mapping chemical and bonding information using multivariate analysis of electron energy-loss spectrum images.

Electron energy-loss spectroscopy (EELS) in the transmission electron microscope (TEM) is used to obtain high-resolution information on the composition and the type of chemical bonding of materials. Spectrum imaging, where a full EEL spectrum is acquired and stored at each pixel in the image, gives an exact correlation of spatial and spectral features. However, determining and extracting the important spectral components from the large amount of information contained in a spectrum image (SI) can be difficult. This paper demonstrates that principal component analysis of EEL SIs can be used to extract chemically relevant components. With weighted or two-way scaled principal component analysis, both compositional and bonding information can be extracted. Mapping of the chemical variations in a partially reduced titanium dioxide sample and the orientation-dependent bonding in boron nitride and carbon nanotubes are given as examples.