SARS-CoV-2 Genome Sequencing Methods Differ in Their Abilities To Detect Variants from Low-Viral-Load Samples.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic surveillance has been vital in understanding the spread of coronavirus disease 2019 (COVID-19), the emergence of viral escape mutants, and variants of concern. However, low viral loads in clinical specimens affect variant calling for phylogenetic analyses and detection of low-frequency variants, important in uncovering infection transmission chains. We systematically evaluated three widely adopted SARS-CoV-2 whole-genome sequencing methods for their sensitivity, specificity, and ability to reliably detect low-frequency variants. Our analyses reveal that the ARTIC v3 protocol consistently displays high sensitivity for generating complete genomes at low viral loads compared with the probe-based Illumina Respiratory Viral Oligo panel and a pooled long-amplicon method. We show substantial variability in the number and location of low-frequency variants detected using the three methods, highlighting the importance of selecting appropriate methods to obtain high-quality sequence data from low-viral-load samples for public health and genomic surveillance purposes.

Evaluation of the utility of hospital databases to provide data in assessing the quality of strabismus surgery.

AIMS AND BACKGROUND: Rates of re-operation, which may be related to an unsatisfactory surgical outcome, can provide a long-term index of the quality of strabismus surgery. This study aims to evaluate the utility of the Scottish Morbidity Records (SMR1) in determining nature and rates of re-operation for strabismus at the Royal Hospital for Sick Children (RHSC), Glasgow. METHODS: SMR1 data on strabismus surgery performed on children aged between 0 and 17 years at the RHSC, Glasgow, between January 2000 and March 2009 were analysed. RESULTS: In total, 1376 strabismus procedures were carried out on 1274 individuals. The median time between first and subsequent procedures was 19 months; the commonest reasons being under-correction or recurrence. The Kaplan-Meier rate of undergoing re-operation was 7.4% after 9 years with a 95% confidence interval of 5.4-9.9%. CONCLUSIONS: The SMR1 is a useful source of hospital-based and population data. With supplementation from parallel databases, routine administrative databases like the SMR1 can provide better quality data to inform practice.

The association between maternal smoking in pregnancy, other early life characteristics and childhood vision: the Twins Eye Study in Tasmania.

PURPOSE: To investigate the association between maternal smoking in pregnancy, early-life environment and childhood vision. METHODS: Twin and triplet children enrolled in the Twins Eye Study in Tasmania underwent a comprehensive ophthalmic examination and their parents/guardians retrospectively answered a questionnaire regarding crawling, walking and other measures. A subset of these twins was also in the Tasmanian Infant Health Survey, which prospectively collected data on antenatal smoking, gestation, birth weight and other factors. RESULTS: The mean age of the 346 individuals (172 multiple birth sets) at the time of examination was 9.25+/-2.4 years. Mean unaided visual acuity was 0.0 (6/6). The mean spherical equivalent was +0.87D, and decreased with increasing child age (p<0.01). A prospective analysis, accounting for birth set clustering and relevant confounders, showed increasing levels of maternal smoking in the third trimester was associated with poor stereoacuity on the Titmus test (worse (>) than 100'', p=0.05) and Lang test (p=0.001) and also with the presence of esotropia (p=0.02). These associations persisted after adjustment for infant postnatal smoke exposure at one month of age. Poor stereoacuity on Titmus stereo test circles was associated with late age of first crawling (RR=1.23 (1.06, 1.42) p=0.005 per month) and late age of first walking (RR 1.18 (1.05, 1.22) p=0.001 per month). CONCLUSIONS: Antenatal smoking was independently associated with poor stereovision and the presence of esotropia. Poor stereoacuity may be associated with delayed age at first crawling or walking.

Nail-patella syndrome and its association with glaucoma: a review of eight families.

BACKGROUND: Nail-patella syndrome (NPS) is a rare autosomal dominant syndrome, characterised by dysplasia of the nails, patellae, elbows and iliac horns. Mutations in the LMX1B gene were found in four North American families in whom glaucoma cosegregated with NPS. AIMS: To investigate the association of glaucoma with NPS in Australian families and to determine how common NPS is in Australia. METHODS: One family with NPS and glaucoma was identified from the Glaucoma Inheritance Study in Tasmania. A further 18 index cases of NPS were identified from the genetics database for southeastern Australia. Eight of these pedigrees were available for comprehensive glaucoma examination on available family members. DNA was sequenced for mutations in LMX1B. RESULTS: In total, 52 living cases of NPS were identified suggesting a minimum prevalence of at least 1 in 100 000. 32 subjects from eight NPS pedigrees (four familial and four sporadic cases) were examined. 14 subjects had NPS alone. 4 subjects had NPS and glaucoma or ocular hypertension. Five pedigrees with NPS had a reported family history of glaucoma, although some of these people with glaucoma did not have NPS. LMX1B mutations were identified in 5 of the 8 index cases-three sporadic and two familial. Two of the six (33%) participants over 40 years of age had developed glaucoma, showing increased risk of glaucoma in NPS. CONCLUSION: Patients with NPS should be examined regularly for glaucoma. However, because the families with NPS are ascertained primarily from young probands or probands who are isolated cases, the exact level of risk is unclear.

Phase I/II trial of cyclophosphamide, mitoxantrone, and escalated doses of carboplatin supported by peripheral-blood stem cells in women with metastatic breast cancer.

PURPOSE: To intensify a regimen of high-dose cyclophosphamide, mitoxantrone, and carboplatin that had previously produced high complete and overall response rates in metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-four patients with a median age of 43 years (range, 25 to 57 years) and previously untreated MBC who were responding to anthracycline-based or single-agent taxane chemotherapy received cyclophosphamide 1.5 g/m(2)/d and mitoxantrone 16 mg/m(2)/d combined with escalating doses of carboplatin 200 to 500 mg/m(2)/d, each given daily from days -6 to -3. Hematopoiesis was supported by mobilized peripheral-blood stem cells infused on day 0 and by use of granulocyte-macrophage colony-stimulating factor 300 microg/d subcutaneously starting on day 1. RESULTS: A total of six dose levels of carboplatin were examined. Grades 3 and 4 toxicity occurred in 10 patients and one patient, respectively, with grade 3 toxicity occurring in only five of 31 patients treated with < or = 400 mg/m(2) of carboplatin. Major dose-limiting toxicities were cardiac, pulmonary, and renal. Four patients developed congestive heart failure: two had persistently low ejection fraction 11 and 36 months after peripheral-blood stem-cell transplantation (PBSCT), and two recovered. Hematologic recovery to an absolute neutrophil count of greater than 0.5 x 10(9)/L occurred at a median of 11 days (range, 8 to 25 days) and to a platelet count of greater than 20 x 10(9)/L at a median of 10.5 days (range, 6 to 60 days). There were two toxic deaths from sepsis: one on day 27 (level 5) and one from cardiac arrest on day 42 (level 6). CONCLUSION: The maximum-tolerated dose of carboplatin was 400 mg/m(2)/d in combination with mitoxantrone 16 mg/m(2)/d and cyclophosphamide 1,500 mg/m(2), all drugs given over 4 days. This regimen is being tested in a phase III trial of high-dose chemotherapy and PBSCT versus standard treatment.

Cancer in south Florida Hispanic women. A 9-year assessment.

BACKGROUND: Cancer incidence varies among race and ethnic subgroups. Relatively little information exists on cancer among Hispanics, and none of it it stratified by race. METHODS: To explore and compare cancer incidence rates of each site of cancer among white Hispanic, white non-Hispanic, black Hispanic, and black non-Hispanic women in Dade County, South Florida, we accessed 9 years of cancer incidence data. Dade County's Hispanic population is the second largest of any US county. For each site, incidence rates, rate ratios, and 95% confidence intervals are presented. RESULTS: Among white Hispanics, there were statistically significant lower rates of cancers of the oral cavity, esophagus, colon, pancreas, lung, breast, ovary, bladder, kidney, melanoma, Kaposi's sarcoma, and non-Hodgkin's lymphoma than among white non-Hispanics. Black Hispanics had significantly lower rates of cancers of the oral cavity, stomach, rectum, lung, cervix, and bladder than black non-Hispanics. However, white Hispanic women had significantly higher rates of cancers of the liver, gallbladder, and uterine cervix than white non-Hispanic women. No in situ breast cancer cases among blacks of either ethnic subgroup was found. CONCLUSION: Both white Hispanic and black Hispanic women generally had lower rates of cancer than their race-specific non-Hispanic counterparts. However, incidence rates among Hispanics differ substantially by race; failure to distinguish them may lead to erroneous conclusions.

Cancer among Hispanic males in south Florida. Nine years of incidence data.

BACKGROUND: Dade County (Florida) is the largest county in the United States in which a majority of the population is Hispanic. To describe and compare cancer incidence among white and black Hispanic and non-Hispanic males in South Florida and to identify those sites showing important racial-ethnic differences between sub-groups, incidence rates were determined from 9 years of prospective population-based cancer surveillance data. METHODS: All incident cancer cases diagnosed among male residents of Dade County for the period January 1, 1981, through December 31, 1989, were obtained from the statewide tumor registry for Florida, the Florida Cancer Data System. Race- and ethnic-specific age-standardized incidence rates and standardized rate ratios to compare rates among racial-ethnic subgroups for each site are presented. RESULTS: Compared with white non-Hispanics, white Hispanic males had significantly higher rates of cancers of the liver, gallbladder, nasal cavity, penis, and thyroid; acute lymphocytic leukemia; and Kaposi's sarcoma. Significantly lower rates were found for cancers of the esophagus, stomach, colon, rectum, pancreas, lung, testes, bladder, and kidney, and for mesothelioma, melanoma, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia. Black Hispanics had significantly lower rates only of cancers of the esophagus, lung, and prostate than did black non-Hispanics. CONCLUSION: Differences were found in incidence rates by race-ethnicity; while incidence rates for most sites among white Hispanic males were lower than among white non-Hispanics, higher rates for several sites are of particular concern and merit further investigation to determine differences in risk factors and exposures.

Spatial asynchrony and periodic travelling waves in cyclic populations of field voles.

We demonstrate evidence for the presence of travelling waves in a cyclic population of field voles in northern Britain by fitting simple, empirical models to spatially referenced time series data. Population cycles were broadly synchronous at all sites, but use of Mantel correlations suggested a strong spatial pattern along one axis at a projection line 72 degrees from North. We then fitted a generalized additive model to log population density assuming a fixed-form travelling wave in one spatial dimension for which the density at each site was offset in time by a constant amount from a standard density-time curve. We assumed that the magnitude of this offset would be proportional to the spatial separation between any given site and the centroid of the sampling sites, where separation is the distance between sites in a fixed direction. After fitting this model, we estimated that the wave moved at an average speed of 19 km yr-1, heading from West to East at an angle of 78 degrees from North. Nomadic avian predators which could synchronize populations over large areas are scarce and the travelling wave may be caused by density-dependent dispersal by field voles and/or predation by weasels, both of which act at a suitably small spatial scale.

Concurrent weekly carboplatin and radiotherapy for nasopharyngeal carcinoma: report of a joint phase II study.

We report a phase I/II study of weekly concurrent carboplatin and radiotherapy in patients with nasopharyngeal carcinoma (M0 stage). Of 47 patients registered, 45 completed the treatment course. Twenty-six (55%) (95% CI, 41-69%) patients experienced > or =grade 3 acute toxicity (RTOG). Five (11%) (95% CI, 2-20%) patients experienced > or =grade 3 chronic toxicity. This regimen appears to have acceptable toxicity compared to the experimental arm of Phase III Intergroup Study 0099, but progression-free and overall survival are probably inferior. At present, there is no data to suggest that carboplatin can replace cisplatin for concurrent chemoradiation for NPC.

Safety of therapeutic anticoagulation in patients with multiple myeloma receiving autologous stem cell transplantation.

The use of autologous stem cell transplantation (ASCT) for the treatment of multiple myeloma is increasing. Anticoagulation may be required during ASCT for conditions such as Hickman line thrombosis. The safety of anticoagulation in patients receiving ASCT is unknown. We report a retrospective case-control study of the safety of therapeutic anticoagulation in patients with multiple myeloma receiving ASCT. We identified 10 patients who received therapeutic anticoagulation during ASCT. For each of the 10 cases identified, two matched controls were selected. As a primary endpoint, bleeding complications were assessed. Secondary endpoints included survival, length of hospital stay, transfusion requirements, grade 4 toxicity, and days to platelet engraftment. Bleeding complications were not significantly different between patients receiving anticoagulation and controls (P = 0.3). Three of 10 anticoagulated patients and two of 20 controls had a bleeding complication. Mortality during admission was similar (P = 1.0); one anticoagulated patient and one control died of sepsis. A trend towards increased median number of platelet transfusions in the heparinized patients was seen (27 vs 12 units, P = 0.055), reflecting the higher transfusion threshold chosen for the anticoagulated patients. The other secondary endpoints did not differ between patients and controls. In this case control study, bleeding was not significantly increased in the group receiving anticoagulation during ASCT. This group electively received more units of platelets than controls. Thus, therapeutic anticoagulation can be managed with minimal increased toxicity during ASCT.

Naloxone does not consistently affect inhibition of spinal nociceptive transmission produced by medial diencephalic stimulation in the cat.

In cats anesthetized with sodium pentobarbital and artificially ventilated with 70% N2O, the response of single lumbar dorsal horn units to noxious radiant heat stimuli (50 degrees C, 10 sec) applied to glabrous footpad skin were recorded with microelectrodes. Unit heat-evoked responses were markedly suppressed by electrical stimulation (100 msec pulse trains at 100 Hz, 3/sec, 50-300 microA) at sites in the medial basal diencephalic periventricular gray, lateral hypothalamic area, preoptic area, and posterior basal telencephalon. Inhibition of dorsal horn unit responses produced by brain stimulation was not consistently affected following systemic administration of the opiate antagonist naloxone (0.5-1 mg/kg i.v.), indicating that the endogenous opioid peptides are not primarily involved in the mediation of this descending inhibition under the experimental conditions.

Altered L-selectin expression in lymphocytes and increased adhesion to endothelium in patients with diabetic retinopathy.

AIM: To investigate L-selectin expression and shedding in patients with and without retinopathy and to determine if any observed changes are reflected by a functional change in the adhesion of leucocytes to an endothelial monolayer. METHODS: Age matched diabetic patients (26 with retinopathy, 19 without retinopathy) were compared to 24 non-diabetic controls to determine L-selectin surface protein expression, L-selectin mRNA production, and serum L-selectin levels by flow cytometry, RT-PCR, and ELISA, respectively. An adhesion assay was used to determine the binding of lymphocytes from the respective test groups to a monolayer of human endothelial cells. RESULTS: Significantly reduced (p = 0.004) L-selectin expression was demonstrated on lymphocytes (CD3+) from patients with diabetes compared to controls, the lowest levels being found in those with diabetic retinopathy (p = 0.004). L-selectin mRNA levels (p = 0.007) were significantly higher in the retinopathy group than in the no retinopathy group. Serum L-selectin levels were significantly higher (p = 0.04) in those with retinopathy compared to controls. Lymphocyte adhesion relative to control (100%) was essentially unchanged (84.0% (SD 27.7%), p = 0.15) for diabetic patients with no retinopathy and was markedly increased (192% (37.6%)) for those with retinopathy (p = 0.0001). CONCLUSION: Lymphocyte activation, reduced surface L-selectin, increased circulating L-selectin, and a corresponding increase in adhesion of patients' cells using an in vitro assay, is evident in people with diabetic retinopathy. This suggests a role for lymphocyte activation in the pathogenesis of diabetic retinopathy.

Chronic pain in the elderly: occupational adaptation as a means of coping with osteoarthritis of the hip and/or knee.

OBJECTIVE: To determine whether elderly individuals with chronic pain as a result of osteoarthritis of the hip and/or knee would report adaptations to their activities, or occupational adaptations, as a coping response to pain and, if so, to describe these adaptations and their relation to chronic pain, functional difficulty, depression, social support, and life satisfaction. DESIGN: Thirty elderly individuals completed rating scales and a structured questionnaire designed to measure occupational adaptation and the importance of activity. SETTING: Participants were community-dwelling elderly individuals and were interviewed in their homes or in a research office setting. PATIENTS: Consecutive orthopedic surgeon, family physician, or Arthritis Society patients, whose names were provided with the patient's consent, to the researcher. RESULTS: Individuals reported two approaches to occupational adaptation: they changed how they performed personal activities of daily living that they rated as most important and they stopped performing a number of avocational activities that they rated as less important. Statistically significant correlations were found among occupational adaptation, pain, depression, and difficulty with functioning. These variables were inversely related to life satisfaction. CONCLUSIONS: This sample of elderly individuals with chronic pain described occupational adaptations, or adaptations to "doing," as a means of coping with their chronic pain. There appeared to be a relation among pain, functional difficulty, depression, social support, and occupational adaptation. Additional research to increase the understanding of occupational adaptation as a means of coping with chronic pain is warranted.

Role of ultrasound biomicroscopy in managing pseudophakic pupillary block glaucoma.

We describe a case of anterior capsule adherence to the iris that occurred after phacoemulsification with in-the-bag intraocular lens (IOL) implantation. This adherence led to the development of pseudophakic pupillary block glaucoma. There were no synechias at the pupillary margin associated with the capsule-iris adherence. Ultrasound biomicroscopy, used to evaluate the anterior segment in vivo, clarified the mechanism of pseudophakic pupillary block. The pupillary block was relieved by a single laser iridotomy.

The proper use and benefits of veterinary antimicrobial agents in swine practice.

There are three main reasons for using antimicrobial agents in pig production: animal welfare, carcase quality and economics. The need to treat sick animals and to mitigate the effects of infection is of paramount humanitarian importance. The reduction of the pathological effects of infection is an essential aspect of carcase quality and of possible value in the control of potential zoonoses. It is beyond dispute that the judicious use of antimicrobial agents improves growth efficiency. In addition there are economic benefits to be gained from the control of infection in terms of improved carcase quality and reduced mortality. When antimicrobial agents are used, careful consideration must be given to their choice. An understanding of the disease complexes of pig herds, of pharmacokinetics and of methods of administration is necessary to achieve safe and cost-effective medication. Bacterial resistance to antimicrobial agents in pig production is of importance only in special circumstances where eradication of a disease is being attempted. Veterinarians specialising in pig production are concerned that there is a climate of restriction of use and availability of suitable agents which could jeopardize animal health and welfare.

Long-term glioblastoma multiforme survivors: a population-based study.

BACKGROUND: Long-term glioblastoma multiforme survivors (LTGBMS) are uncommon. The frequency which these occur in an unselected population and factors which produce these unusually long survivors are unknown. OBJECTIVES: To determine in a population-based study 1) the frequency of LTGBMS in a population and 2) identify which patient, treatment or tumor characteristics would predict which glioblastoma (GBM) patient would become a LTGBMS. METHODS: The Alberta Cancer Registry was used to identify all patients diagnosed with GBM in southern Alberta between 1/1/75-12/31/91. Patient charts were reviewed and histology re-examined by a blinded neuropathologist. LTGBMS were defined as GBM patients surviving > or = 3 years after diagnosis. Each LTGBMS was compared to three age-, gender-, and year of diagnosis-matched controls to compare patient, treatment, and tumor factors to GBM patients without long-term survival. RESULTS: There were 279 GBMs diagnosed in the study period. Five (1.8%) survived > or = three years (range, 3.2-15.8 years). Seven additional long-term survivors, who carried a diagnosis of GBM, were excluded after neuropathologic review; the most common revised diagnosis was malignant oligodendroglioma. LTGBMS (avg. age = 45 years) were significantly younger when compared to all GBM patients (avg. age = 59 years, p = 0.0001) diagnosed in the study period. LTGBMS had a higher KPS at diagnosis (p = 0.001) compared to controls. Tumors from LTGBMS tended to have fewer mitoses and a lower Ki-67 cellular proliferative index compared to controls. Radiation-induced dementia was common and disabling in LTGBMS. CONCLUSIONS: These data highlight the dismal prognosis for GBM patients who have both a short median survival and very small chance (1.8%) of long-term survival. The LTGBMS were younger, had a higher performance status, and their tumors tended to proliferate less rapidly than control GBM patients. When long-term survival does occur it is often accompanied by severe treatment-induced dementia.

Ultraviolet light treatment of a patient with pityriasis lichenoides et varioliformis acuta (Mucha-Habermann disease). A case report.

The purpose of this case report is to detail the physical therapy of a patient with pityriasis lichenoides et varioliformis acuta (Mucha-Habermann disease), a condition usually not encountered by physical therapists. Prolonged exposure to ultraviolet light was the effective mode of treatment.

Study of Doppler ultrasonic peripheral vascular assessments performed by physical therapists.

The Doppler ultrasound assessment is an effective diagnostic method for determining peripheral vascular status. Because the evaluation currently is not often performed by a physical therapist, the purpose of this study was to provide objective information on the competency of a group of physical therapists who were doing these evaluations. Therapists at a state psychiatric hospital in North Carolina performed a total of 577 Doppler assessments from May 1976 to May 1981. Forty-eight of these evaluations were followed by an invasive peripheral vascular diagnostic technique, either a venogram or an arteriogram. When Doppler results were compared with invasive results, 85 percent of the Doppler evaluations agreed with results obtained using the invasive techniques. There was complete agreement with arterial evaluations, and 81 percent agreement with venous assessments. These results support the contention that Doppler ultrasonic evaluations of peripheral vascular disease can be competently performed by physical therapists trained in the technique.