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Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

Abstract High resolution force measurements of molecules on surfaces, in non-contact atomic force microscopy, are often only performed at cryogenic temperatures, due to needing a highly stable system, and a passivated probe tip (typically via CO-functionalisation). Here we show a reliable protocol for acquiring three-dimensional force map data over both single organic molecules and assembled islands of molecules, at room temperature. Isolated cobalt phthalocyanine and islands of C60 are characterised with submolecular resolution, on a passivated silicon substrate (B:Si(111)- $$(\sqrt{3}\times \sqrt{3})R3{0}^{\circ }$$ ( 3 × 3 ) R 3 0 ∘ ). Geometries of cobalt phthalocyanine are determined to a ~ 10 pm accuracy. For the C60, the protocol is sufficiently robust that areas spanning 10 nm × 10 nm are mapped, despite the difficulties of room temperature operation. These results provide a proof-of-concept for gathering high-resolution three-dimensional force maps of networks of complex, non-planar molecules on surfaces, in conditions more analogous to real-world application.

School counseling interns rose to the task of teaching full-time while earning hours for their internship course during COVID-19. For this qualitative study, the researchers conducted a focus group with eight graduates who successfully completed their internship in Fall 2021 or Spring 2022 amid the pandemic. The purpose of this exploratory, inductive, qualitative research study was to examine the role of grit in successful completion of Internship requirements among school counselor trainees who were enrolled in Internship during some of the worst months of the COVID-19 pandemic. Criterion and convenience sampling were utilized for participant recruitment. After the interviews were transcribed, the authors utilized thematic content analysis and identified six overarching themes. Following themes were identified: a) personal characteristics of grit, b) observations about gritty individuals, c) internal internship challenges, d) external internship challenges, e) internal contributors to internship success, f) external contributors to internship success. The authors present results on the participants’ perceptions of their experiences during internship to offer an enhanced description of the phenomenon of grit. Implications were provided for students, educators, and programs to foster grit as a contributing factor for student success and overall well-being

The spring and summer of 2019–2020 (Black Summer) saw the largest and most significant bushfire outbreak recorded in eastern Australia. In Victoria, the fires ran from mid-November through early autumn. In this paper, we use a high-spatial and temporal resolution 48-year fire weather re-analysis data set (VicClim5) to describe fire weather and vertical wind and stability profiles for five significant high Forest Fire Danger Index (FFDI) fire events and compare these with detailed fire reconstructions. A feature of several of these fires was very active overnight fire spread driven by topographically enhanced low-level jets and low fine fuel moisture content. The FFDI values on these nights were either the highest or near highest on record in the 48-year data set. We describe cases of lightning ignition, prefrontal fire spread and two cases of post-frontal fire spread – one into Mallacoota on the early morning of 31 December 2019 and the other a northward overnight run down the Buffalo Valley on 4–5 January 2020. On two of the days studied there were complex wind changes associated with the inland penetration of low-level south-easterly winds under the influence of locally generated pressure gradients. An elevated hot, dry mixed layer above these shallow layers also played an important role. On one occasion there is some evidence of possible mountain-wave modulation of surface wind flows. These events demonstrate a range of features of the fire weather and climate in eastern Victoria and the utility of VicClim5 in 3-dimensional climatological analyses.

Summary: Deciphering the function of neural circuits can help with the understanding of brain function and treating neurological disorders. Progress toward this goal relies on the development of chronically stable neural interfaces capable of recording and modulating neural circuits with high spatial and temporal precision across large areas of the brain. Advanced innovations in designing high-density neural interfaces for small animal models have enabled breakthrough discoveries in neuroscience research. Developing similar neurotechnology for larger animal models such as nonhuman primates (NHPs) is critical to gain significant insights for translation to humans, yet still it remains elusive due to the challenges in design, fabrication, and system-level integration of such devices. This review focuses on implantable surface neural interfaces with electrical and optical functionalities with emphasis on the required technological features to realize scalable multimodal and chronically stable implants to address the unique challenges associated with nonhuman primate studies.

Depressive disorders are a leading cause of disability and are globally pervasive. It is estimated that 80% of depression occurs in low-income and middle-income countries. Depression is associated with worse outcomes in patients with cardiac disease including heart failure (HF); however, mechanistic understanding to explain heightened risk in HF remains poorly characterized. We examined the association between depressive symptoms and cardiac structure and function by transthoracic echocardiography. We selected a random sample of adult participants in Puno and Pampas de San Juan de Miraflores, Peru, from the CRONICAS cohort study. Depression symptoms were self-reported and measured with the Center for Epidemiological Studies Depression Scale in 2010. Participants underwent transthoracic echocardiography in 2014. Multivariable linear regression was used to examine the relationship between depressive symptoms and echocardiographic measures of cardiac structure and function and was adjusted for relevant covariates. Three hundred and seventy-three participants (mean age 56.7 years, 57% female) were included in this analysis of which 91 participants (24%) had clinically significant depressive symptoms. After adjustment, clinically significant depressive symptoms were associated with a reduced diastolic relaxation velocity compared to non-depressed subjects (–0.72 cm/s, 95% CI –1.21 to –0.24, p = 0.004). Other differences between depressed and non- depressed participants were less obvious. In conclusion, clinically significant depressive symptoms were associated with a lower septal e’ velocity in the Peruvian population. Depressive symptoms were not obviously associated with other abnormalities in cardiac structure or function.

The National Weather Service is responsible for alerting wildland fire management of meteorological conditions that create an environment conducive for extreme fire behavior. This is communicated via Red Flag Warnings (RFWs), which presently lack a national standardized methodology and rarely are explicitly linked to fuel conditions such those as provided by National Fire-Danger Rating System (NFDRS) indicators. The need for a revamped RFW has been expressed recently by both fire management and fire weather meteorologists. A decision matrix approach was developed to determine criteria that consistently and explicitly associates meteorological and fuels information to extreme fire behavior. Extreme fire behavior is defined here as maximum rates of spread (area per day) observed on documented large fires from 1999–2014 utilizing the ICS209 all-hazard dataset. Meteorological conditions occurring with these rates of spread were compared to historical percentiles of relative humidity, wind speed, and the NFDRS Energy Release Component. These percentiles were assigned a numerical score from one through five based on percentile rank. The additive result of all three scores was plotted against rates of spread yielding a two-step decision matrix of RFW categories where, for example, the highest score is the most extreme RFW case. Actual RFW issuances were compared to this matrix method.

Wind changes are a critical factor in fire management, particularly on days of elevated fire danger, and have been shown to be a factor in many firefighter entrapments in Australia and the USA. While there have been numerous studies of frontal wind changes over southeastern Australia since the 1950s, a spatial climatology of wind change strength and frequency over Victoria has hitherto been limited by the relatively low number of observation sites that have both high temporal resolution observations and sufficient length of record. This study used a recently developed high spatial (4-km grid) and temporal (1hour) resolution, 46-year, homogeneous gridded fire weather climatology data set to generate a climatology of wind change strength by season at each gridpoint across Victoria. The metric used to define a wind change is the vector difference between the wind speed and direction over each 1-hour interval, with the highest value occuring on each day being selected for spatial analysis of strength and frequency. The highest values of wind change strength are found along the crest of the Great Dividing Range (the Great Divide), with a peak in spring. Elsewhere, the highest values occur in summer, with the areas south of the Great Divide, west of Melbourne and in central Gippsland showing higher values than the remainder of the state. The strength of wind changes generally decreases north of the Great Divide, although it is stronger in the northwest of the state in spring rather than in autumn. Lowest summertime (and other seasons) values occur in the northeast of the state and in far-east Gippsland. Exploring the frequencies of days when the highest daily Forest Fire Danger Index and the highest daily wind change strength jointly exceed defined thresholds shows that the northwest of the state has the highest springtime frequencies, whereas the highest autumn frequencies occur west of Melbourne and south of the Great Divide. The highest numbers of joint events in summer (when the greatest frequencies also occur) extend from central Victoria west to the South Australian border, with a secondary maximum in central Gippsland. These analyses offer important information for fire weather forecasters and for fire practitioners when preparing for a fire season or managing a fire campaign (for example, for allocating resources or understanding risks).

Circadian rhythms in mammals are orchestrated by a central clock within the suprachiasmatic nuclei (SCN). Our understanding of the electrophysiological basis of SCN activity comes overwhelmingly from a small number of nocturnal rodent species, and the extent to which these are retained in day-active animals remains unclear. Here, we recorded the spontaneous and evoked electrical activity of single SCN neurons in the diurnal rodent Rhabdomys pumilio, and developed cutting-edge data assimilation and mathematical modeling approaches to uncover the underlying ionic mechanisms. As in nocturnal rodents, R. pumilio SCN neurons were more excited during daytime hours. By contrast, the evoked activity of R. pumilio neurons included a prominent suppressive response that is not present in the SCN of nocturnal rodents. Our modeling revealed and subsequent experiments confirmed transient subthreshold A-type potassium channels as the primary determinant of this response, and suggest a key role for this ionic mechanism in optimizing SCN function to accommodate R. pumilio’s diurnal niche.

This paper examines the problem of diffeomorphic image registration in the presence of differing image intensity profiles and sparsely sampled, missing, or damaged tissue. Our motivation comes from the problem of aligning 3D brain MRI with 100-micron isotropic resolution to histology sections at 1 × 1 × 1,000-micron resolution with multiple varying stains. We pose registration as a penalized Bayesian estimation, exploiting statistical models of image formation where the target images are modeled as sparse and noisy observations of the atlas. In this injective setting, there is no assumption of symmetry between atlas and target. Cross-modality image matching is achieved by jointly estimating polynomial transformations of the atlas intensity. Missing data is accommodated via a multiple atlas selection procedure where several atlas images may be of homogeneous intensity and correspond to “background” or “artifact.” The two concepts are combined within an Expectation-Maximization algorithm, where atlas selection posteriors and deformation parameters are updated iteratively and polynomial coefficients are computed in closed form. We validate our method with simulated images, examples from neuropathology, and a standard benchmarking dataset. Finally, we apply it to reconstructing digital pathology and MRI in standard atlas coordinates. By using a standard convolutional neural network to detect tau tangles in histology slices, this registration method enabled us to quantify the 3D density distribution of tauopathy throughout the medial temporal lobe of an Alzheimer's disease postmortem specimen.

Abstract Background Lapatinib is a tyrosine kinase inhibitor that blocks the HER2 receptor and is typically used in the setting of metastatic breast cancer. Both ERBB2 (HER2) and ERBB3 (HER3) belong to the same family of receptor tyrosine kinases. Dimerization of these receptors leads to activation of cell proliferation and survival pathways, granting oncogenic potential to dysregulated ERBB/HER receptors. Next generation sequencing (NGS) of tumors has ushered in a new era of personalized oncology therapy and has the ability to detect mutations in ERBB receptors. Case presentation We present a patient with metastatic cutaneous squamous cell carcinoma who failed surgery, radiation, and anti-PD1 therapy, but showed clinical response to a drug targeting an ERBB3 mutation identified with NGS. Following initiation of the drug lapatinib, this patient exhibited dramatic tumor regression in the skin, soft tissue, bone and nerves. Conclusions Cutaneous squamous cell carcinoma is the 2nd most common skin cancer in humans and future investigation of ERBB2 targeted therapies may provide an effective treatment strategy for patients with mutations in the ERBB2/3 pathway.

Background: An anatomical covariance analysis (ACA) enables to elucidate inter-regional connections on a group basis, but little is known about the connections among white matter structures or among gray and white matter structures. Effect of including multiple magnetic resonance imaging (MRI) modalities into ACA framework in detecting white-to-white or gray-to-white connections is yet to be investigated. New method: Proposed extended anatomical covariance analysis (eACA), analyzes correlations among gray and white matter structures (multi-structural) in various types of imaging modalities (T1-weighted images, T2 maps obtained from dual-echo sequences, and diffusion tensor images (DTI)). To demonstrate the capability to detect a disruption of the correlation network affected by pathology, we applied the eACA to two groups of cognitively-normal elderly individuals, one with (PiB+) and one without (PiB-) amyloid deposition in their brains. Results: The volume of each anatomical structure was symmetric and functionally related structures formed a cluster. The pseudo-T2 value was highly homogeneous across the entire cortex in the PiB- group, while a number of physiological correlations were altered in the PiB + group. The DTI demonstrated unique correlation network among structures within the same phylogenetic portions of the brain that were altered in the PiB + group. Comparison with Existing Method: The proposed eACA expands the concept of existing ACA to the connections among the white matter structures. The extension to other image modalities expands the way in which connectivity may be detected. Conclusion: The eACA has potential to evaluate alterations of the anatomical network related to pathological processes.

This study examines the atrophy rates of subjects with mild cognitive impairment (MCI) compared to controls in four regions within the medial temporal lobe: the transentorhinal cortex (TEC), entorhinal cortex (ERC), hippocampus, and amygdala. These regions were manually segmented and then corrected for undesirable longitudinal variability via Large Deformation Diffeomorphic Metric Mapping (LDDMM) based longitudinal diffeomorphometry. Diffeomorphometry techniques were used to compare thickness measurements in the TEC with the ERC. There were more significant changes in thickness atrophy rate in the TEC than medial regions of the entorhinal cortex. Volume measures were also calculated for all four regions. Classifiers were constructed using linear discriminant analysis to demonstrate that average thickness and atrophy rate of TEC together was the most discriminating measure compared to the thickness and volume measures in the areas examined, in differentiating MCI from controls. These findings are consistent with autopsy findings demonstrating that initial neuronal changes are found in TEC before spreading more medially in the ERC and to other regions in the medial temporal lobe. These findings suggest that the TEC thickness could serve as a biomarker for Alzheimer's disease in the prodromal phase of the disease. Keywords: Entorhinal cortex, Transentorhinal cortex, Mild cognitive impairment, Braak staging, Cortical thickness, Shape analysis, Longitudinal analysis

Huntington disease (HD) is a fatal progressive neurodegenerative disorder for which only symptomatic treatment is available. A better understanding of the pathology, and identification of biomarkers will facilitate the development of disease-modifying treatments. HD is potentially a good model of a neurodegenerative disease for development of biomarkers because it is an autosomal-dominant disease with complete penetrance, caused by a single gene mutation, in which the neurodegenerative process can be assessed many years before onset of signs and symptoms of manifest disease. Previous MRI studies have detected abnormalities in gray and white matter starting in premanifest stages. However, the understanding of how these abnormalities are related, both in time and space, is still incomplete. In this study, we combined deep gray matter shape diffeomorphometry and white matter DTI analysis in order to provide a better mapping of pathology in the deep gray matter and subcortical white matter in premanifest HD. We used 296 MRI scans from the PREDICT-HD database. Atrophy in the deep gray matter, thalamus, hippocampus, and nucleus accumbens was analyzed by surface based morphometry, and while white matter abnormalities were analyzed in (i) regions of interest surrounding these structures, using (ii) tractography-based analysis, and using (iii) whole brain atlas-based analysis. We detected atrophy in the deep gray matter, particularly in putamen, from early premanifest stages. The atrophy was greater both in extent and effect size in cases with longer exposure to the effects of the CAG expansion mutation (as assessed by greater CAP-scores), and preceded detectible abnormalities in the white matter. Near the predicted onset of manifest HD, the MD increase was widespread, with highest indices in the deep and posterior white matter. This type of in-vivo macroscopic mapping of HD brain abnormalities can potentially indicate when and where therapeutics could be targeted to delay the onset or slow the disease progression.

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia are preceded by a phase of disease, referred to as ‘preclinical AD’, during which cognitively normal individuals have evidence of AD pathology in the absence of clinical impairment. This study examined whether a magnetic resonance imaging (MRI) measure of cortical thickness in brain regions, collectively known as ‘AD vulnerable’ regions, predicted the time to onset of clinical symptoms associated with MCI and whether cortical thickness was similarly predictive of clinical symptom onset within 7 years post baseline versus progression at a later point in time. These analyses included 240 participants from the BIOCARD study, a cohort of longitudinally followed individuals who were cognitively normal at the time of their MRI (mean age = 56 years). Participants have been followed for up to 18 years (M follow-up = 11.8 years) and 50 participants with MRIs at baseline have developed MCI or dementia over time (mean time to clinical symptom onset = 7 years). Cortical thickness in AD vulnerable regions was based on the mean thickness of eight cortical regions. Using Cox regression models, we found that lower mean cortical thickness was associated with an increased risk of progression from normal cognition to clinical symptom onset within 7 years of baseline (p = 0.03), but not with progression >7 years from baseline (p = 0.30). Lower cortical thickness was also associated with higher levels of phosphorylated tau, measured in cerebrospinal fluid at baseline. These results suggest that cortical thinning in AD vulnerable regions is detectable in cognitively normal individuals several years prior to the onset of clinical symptoms that are a harbinger of a diagnosis of MCI, and that the changes are more likely to be evident in the years proximal to clinical symptom onset, consistent with hypothetical AD biomarker models.

Involvement of parents plays a crucial role in the implementation of a comprehensive school counseling program. For this study, 404 parents participated in a national survey conducted in the United States. The purpose of the study was to investigate parents' perceptions of their involvement with the school counseling program and their relationship with the school counselor. Results suggested concerns regarding school counselor communication and the involvement of parents in their child's education and planning after high school. Results also indicated participants held a positive perception of school counselors (e.g., hopeful, positive, and accepting), their competency, and they felt comfortable with the school counselor.

While there seems to be growing media intrigue over atypical forms of alcohol use, the utilization of the majority of novel consumption methods (e.g., eyeballing, slimming, alcohol without liquid (AWOL)) seems minimal. In 2014, however, several outlets suggested that powdered alcohol would soon surface as a threat to public safety. The impetus of these fears was the Alcohol and Tobacco Tax and Trade Bureau’s approval for Lipsmark LLC to package a powdered alcohol product named “Palcohol”. Palcohol has yet to reach store shelves, but public outcry has been intense. Despite this reaction, little is known about whether the population will consider Palcohol a suitable alternative to traditional alcohol, particularly given its excessive predicted cost. In an exploratory effort to assess perceptions, use intentions, and fears related to Palcohol, 31 young adults were asked to view a 16-minute video about Palcohol and answer a series of questions about Palcohol, including whether and how they intend to use it. Results suggest that young adults intend to experiment with Palcohol following its release, but they have a number of concerns. While few expect to become habitual users of the product, many believe it will enable people to utilize alcohol in settings where its consumption is prohibited.

A large isoniazid-resistant tuberculosis outbreak centred on London, United Kingdom, has been ongoing since 1995. The aim of this study was to investigate the power and value of whole genome sequencing (WGS) to resolve the transmission network compared to current molecular strain typing approaches, including analysis of intra-host diversity within a specimen, across body sites, and over time, with identification of genetic factors underlying the epidemiological success of this cluster.We sequenced 344 outbreak isolates from individual patients collected over 14 y (2 February 1998-22 June 2012). This demonstrated that 96 (27.9%) were indistinguishable, and only one differed from this major clone by more than five single nucleotide polymorphisms (SNPs). The maximum number of SNPs between any pair of isolates was nine SNPs, and the modal distance between isolates was two SNPs. WGS was able to reveal the direction of transmission of tuberculosis in 16 cases within the outbreak (4.7%), including within a multidrug-resistant cluster that carried a rare rpoB mutation associated with rifampicin resistance. Eleven longitudinal pairs of patient pulmonary isolates collected up to 48 mo apart differed from each other by between zero and four SNPs. Extrapulmonary dissemination resulted in acquisition of a SNP in two of five cases. WGS analysis of 27 individual colonies cultured from a single patient specimen revealed ten loci differed amongst them, with a maximum distance between any pair of six SNPs. A limitation of this study, as in previous studies, is that indels and SNPs in repetitive regions were not assessed due to the difficulty in reliably determining this variation.Our study suggests that (1) certain paradigms need to be revised, such as the 12 SNP distance as the gold standard upper threshold to identify plausible transmissions; (2) WGS technology is helpful to rule out the possibility of direct transmission when isolates are separated by a substantial number of SNPs; (3) the concept of a transmission chain or network may not be useful in institutional or household settings; (4) the practice of isolating single colonies prior to sequencing is likely to lead to an overestimation of the number of SNPs between cases resulting from direct transmission; and (5) despite appreciable genomic diversity within a host, transmission of tuberculosis rarely results in minority variants becoming dominant. Thus, whilst WGS provided some increased resolution over variable number tandem repeat (VNTR)-based clustering, it was insufficient for inferring transmission in the majority of cases.

To inform development of tuberculosis (TB) control strategies, we characterized a total of 2,261 Mycobacterium tuberculosis complex isolates by using multiple phenotypic and molecular markers, including polymorphisms in repetitive sequences (spoligotyping and variable-number tandem repeats [VNTRs]) and large sequence and single-nucleotide polymorphisms. The Beijing family was strongly associated with multidrug resistance (p = 0.0001), and VNTR allelic variants showed strong associations with spoligotyping families: >5 copies at exact tandem repeat (ETR) A, >2 at mycobacterial interspersed repetitive unit 24, and >3 at ETR-B associated with the East African–Indian and M. bovis strains. All M. tuberculosis isolates were differentiated into 4 major lineages, and a maximum parsimony tree was constructed suggesting a more complex phylogeny for M. africanum. These findings can be used as a model of pathogen global diversity.

To address conflicting results about the stability of variable number tandem repeat (VNTR) loci and their value in prospective molecular epidemiology of Mycobacterium tuberculosis, we conducted a large prospective population-based analysis of all M. tuberculosis strains in a metropolitan setting. Optimal and reproducible conditions for reliable PCR and fragment analysis, comprising enzymes, denaturing conditions, and capillary temperature, were identified for a panel of hypervariable loci, including 3232, 2163a, 1982, and 4052. A total of 2,261 individual M. tuberculosis isolates and 265 sets of serial isolates were analyzed by using a standardized 15-loci VNTR panel, then an optimized hypervariable loci panel. The discriminative ability of loci varied substantially; locus VNTR 3232 varied the most, with 19 allelic variants and Hunter-Gaston index value of 0.909 unNN. Hypervariable loci should be included in standardized panels because they can provide consistent comparable results at multiple settings, provided the proposed conditions are adhered to.

Mycobacterium bovis caused 3% of human tuberculosis cases in southwest Ireland during 1998–2006. Of 11 M. bovis strains genotyped, 9 belonged to common animal spoligotypes. Seven strains were from sputum and potential sources of human-centered disease transmission. Ten-locus variable-number tandem repeat typing gave unique strain profiles and would detect disease outbreaks.

A high prevalence of tuberculosis (TB) isolates that are genetically homogenous and from the Beijing family has been reported in Russia. To map TB transmission caused by these strains, new genotyping systems are needed. Mycobacterial interspersed repetitive units (MIRUs) offer the possibility of rapid PCR-based typing with comparable discrimination to IS6110 restriction fragment length polymorphism techniques. Spoligotyping and detection of IS6110 insertion in the dnaA-dnaN region were used to identify Beijing strains in 187 Mycobacterium tuberculosis isolates from Samara, Russia. The Beijing isolates were analyzed by using 12-MIRU and 3–exact tandem repeats (ETR) loci and by an expanded set of 10 additional variable number tandem repeats loci. The expanded set of 25 MIRUs provided better discrimination than the original set of 15 (Hunter-Gaston diversity index 0.870 vs 0.625). Loci MIRU 26, 1982, and 3232 were the most polymorphic in Beijing isolates.

The United Kingdom Health Protection Agency Mycobacterium Reference Unit offers a national "Fastrack" molecular service for detecting Mycobacterium tuberculosis complex (MTBC) and rifampin resistance by using the INNO-LiPA Rif.TB assay. We analyzed the service in a routine, nontrial context of 1,997 primary clinical specimens, including 658 nonrespiratory specimens. The overall adjusted concordance, sensitivity, specificity, positive predictive value, and negative predictive value for detecting MTBC were 91.2%, 85.2%, 96.2%, 95.7%, and 86.7%, respectively (unadjusted, 86.7%, 85.2%, 88.2%, 86.9%, and 86.7%), when false-positive samples from patients (n = 83) with a known microbiologic diagnosis of MTBC or patients receiving current or recent antituberculous treatment were excluded. The parameters for detecting rifampin resistance were 99.1%, 95.0%, 99.6%, 92.7%, and 99.7%, respectively. The assay enabled earlier diagnosis of MTBC and rifampin resistance (15.2 days) compared with culture-based techniques (30.7 days).

Consecutive patient cultures (140) of Mycobacteriium tuberculosis were collected from five Russian civilian and prison tuberculosis laboratories and analyzed for rifampin (rpoB) and isoniazid resistance (inhA, katG, ahpC); transmission of Beijing family isolates; and the importance of prison and previous therapy in drug resistance. Rifampin, isoniazid, and multidrug resistance occurred in 58.2%, 51.6%, and 44.7% of cultures, respectively; 80% of prison cultures were rifampin resistant. Spoligotyping and variable number tandem repeat (VNTR) fingerprinting divided the isolates into 43 groups. Spoligotyping demonstrated that a high proportion (68.1%) of patients were infected with Beijing family strains and that most (69.1%) were rifampin resistant; the highest proportion (81.6%) occurred in prison. One VNTR subgroup (42435) comprised 68 (72.3%) of the Beijing isolates with a small number of IS6110 types; 50 (73.5%) were rifampin resistant. Rifampin-resistant Beijing isolates are dominant within the patient population, especially among prisoners, and threaten treatment programs.

This essay has its origin in a project on the globalization of science that rediscovered the wisdom of past research practices through the technology of the future. The main argument of this essay is that a convergence of digital video technologies with practices of social surveillance portends a methodological shift towards a new variety of qualitative methodology. Digital video is changing the way that students of the social world practice their craft, offering not just new ways of presenting but new ways of practicing field research. We introduce concepts of the fluid wall and videoactive context to emphasize that (1) the camera is an actor in the research process, and (2) both behaviour and observation occur in both directions--in front of and behind the camera. While these practices and procedures are novel in some ways, they may also be viewed as old methods in the context of new instruments for recording as well as a new social understanding of these instruments. Since new technologies interact with the social context, the digital video methods we discuss in this essay are likely to become increasingly important for generations to come. We provide an overview of the use of digital video in research practice and present an account of the use of digital video methodology in Chile.