Laser aiming simulation /LASIM/ Final report, Feb. 1967 - May 1968

Laser aiming simulation models for synchronous satellite optical communication system

Phase II trial of tamoxifen and goserelin in recurrent epithelial ovarian cancer

Endocrine therapy is a recognised option in the treatment of chemo-resistant ovarian cancer. We conducted a nonrandomised phase II evaluation of combination endocrine therapy with tamoxifen and goserelin in patients with advanced ovarian cancer that had recurred following chemotherapy. In total, 26 patients entered the study, of which 17 had platinum-resistant disease. The median age was 63 years and enrolled patients had received a median of three chemotherapy regimens prior to trial entry. Patients were given oral tamoxifen 20 mg twice daily on a continuous basis and subcutaneous goserelin 3.6 mg once a month until disease progression. Using the definition of endocrine response that included patients with stable disease (SD) of 6 months or greater, the overall response rate (clinical benefit rate) was 50%. This included one complete response (CR) (3.8%), two partial responses (PR) (7.7%) and 10 patients with SD (38.5%). The median progression-free interval (PFI) was 4 months (95% CI 2.4–9.6) while the median overall survival (OS) was 13.6 months (95% CI 5.5–30.6). Four patients received treatment for more than 2 years (range 1–31) and one of them is still on treatment. In none of the four patients was there any evidence of recurrent or cumulative treatment related toxicity. Treatment-limiting toxicity was not seen in any of the study population. Endocrine data demonstrated a marked suppression of luteinising hormone (LH) and follicle-stimulating hormone (FSH) to less than 4% of baseline values. No consistent correlation could be established between LH/FSH suppression and tumour response. Likewise no relationship was observed between Inhibin A/B and pro-alpha C levels and tumour response. Inhibin is unlikely to be a useful surrogate marker for response in locally advanced or metastatic ovarian cancer. Combination endocrine therapy with tamoxifen and goserelin is an active regimen in platinum-resistant ovarian cancer patients. Hormonal therapy is advantageous in its relative lack of toxicity, ease of administration and tolerability, thus making it suitable for patients with heavily pretreated disease, compromised bone marrow function and other comorbid conditions that contraindicate cytotoxic therapy as well as in patients with indolent disease

Extraspinal osteoarticular multidrug-resistant tuberculosis in children: A case series

Background. South Africa (SA) is known to have a high disease burden of tuberculosis (TB). Extraspinal osteoarticular multidrug-resistant tuberculosis (ESOA MDR-TB) in children has only been described in a few case reports worldwide.Objectives. To describe the epidemiology and highlight the potential problem of ESOA MDR-TB infections as seen in children from a single academic hospital in SA.Methods. A retrospective record review was performed on all children diagnosed with ESOA TB infection at Chris Hani Baragwanath Academic Hospital, Johannesburg, between 1 January 2006 and 31 December 2015. All patients with a positive TB culture (fluid or tissue) from the surgical site of biopsy (bone or joint) and who were hospitalised were included. Organism culture and drug sensitivity testing were performed.Results. Overall 19 cases of ESOA TB were identified. Areas involved included the shoulder (2 cases), elbow (2 cases), hip (7 cases), knee (4 cases), ankle (3 cases) and humerus (1 case). The mean age of the population was 7.7 (range 2.0 - 14.0) years. The mean white cell count was 11.3 (range 5 - 28.9) × 109/L, the mean C-reactive protein level 53.8 (range 1.0 - 364.0) mg/L and the mean erythrocyte sedimentation rate 35.5 (range 4.0 - 85.0) mm/h. Two cases (10.5%) were MDR, and a further case (5.3%) was resistant to isoniazid only. Four of 12 patients tested positive for HIV. One of the HIV-positive patients was isoniazid resistant. The two positive ESOA MDR-TB cases are discussed in detail.Conclusions. These findings indicate that ESOA MDR-TB is a reality in this paediatric population (10.5%) and a high index of suspicion should be maintained, especially when cultures are negative in children with signs and symptoms of ESOA TB. The effect of HIV infection on the incidence of ESOA MDR-TB requires further study.

Outcome of radiotherapy in T1 glottic carcinoma: A population-based study

We evaluated the radiation outcome and prognostic factors in a population-based study of early (T1N0M0) glottic carcinoma. Survival parameters and prognostic factors were evaluated by uni- and multivariate analysis in 316 consecutive irradiated patients with T1 glottic carcinoma in the Comprehensive Cancer Center West region of the western Netherlands. Median follow-up was 70 months (range 1-190 months). Five and ten-year local control was 86 and 84%. Disease specific survival was 97% at 5 and 10 years. In multivariate analysis, pre-existent laryngeal hypertrophic laryngitis was the only predictive factor for local control (relative risk = 3.0, P = 0.02). Comorbidity was prognostic for overall survival. No factor was predictive for disease specific survival. Pre-existent laryngeal hypertrophic laryngitis is a new risk factor associated with reduced local control in T1 glottic carcinoma treated with radiotherapy

Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression.

BACKGROUND: Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infection caused by the delta variant with increasing time since vaccination. METHODS: This study was designed as a systematic review and meta-regression. We did a systematic review of preprint and peer-reviewed published article databases from June 17, 2021, to Dec 2, 2021. Randomised controlled trials of COVID-19 vaccine efficacy and observational studies of COVID-19 vaccine effectiveness were eligible. Studies with vaccine efficacy or effectiveness estimates at discrete time intervals of people who had received full vaccination and that met predefined screening criteria underwent full-text review. We used random-effects meta-regression to estimate the average change in vaccine efficacy or effectiveness 1-6 months after full vaccination. FINDINGS: Of 13 744 studies screened, 310 underwent full-text review, and 18 studies were included (all studies were carried out before the omicron variant began to circulate widely). Risk of bias, established using the risk of bias 2 tool for randomised controlled trials or the risk of bias in non-randomised studies of interventions tool was low for three studies, moderate for eight studies, and serious for seven studies. We included 78 vaccine-specific vaccine efficacy or effectiveness evaluations (Pfizer-BioNTech-Comirnaty, n=38; Moderna-mRNA-1273, n=23; Janssen-Ad26.COV2.S, n=9; and AstraZeneca-Vaxzevria, n=8). On average, vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21·0 percentage points (95% CI 13·9-29·8) among people of all ages and 20·7 percentage points (10·2-36·6) among older people (as defined by each study, who were at least 50 years old). For symptomatic COVID-19 disease, vaccine efficacy or effectiveness decreased by 24·9 percentage points (95% CI 13·4-41·6) in people of all ages and 32·0 percentage points (11·0-69·0) in older people. For severe COVID-19 disease, vaccine efficacy or effectiveness decreased by 10·0 percentage points (95% CI 6·1-15·4) in people of all ages and 9·5 percentage points (5·7-14·6) in older people. Most (81%) vaccine efficacy or effectiveness estimates against severe disease remained greater than 70% over time. INTERPRETATION: COVID-19 vaccine efficacy or effectiveness against severe disease remained high, although it did decrease somewhat by 6 months after full vaccination. By contrast, vaccine efficacy or effectiveness against infection and symptomatic disease decreased approximately 20-30 percentage points by 6 months. The decrease in vaccine efficacy or effectiveness is likely caused by, at least in part, waning immunity, although an effect of bias cannot be ruled out. Evaluating vaccine efficacy or effectiveness beyond 6 months will be crucial for updating COVID-19 vaccine policy. FUNDING: Coalition for Epidemic Preparedness Innovations

The IASLC/ITMIG thymic epithelial tumors staging project: Proposals for the T component for the forthcoming (8th) edition of the TNM classification of malignant tumors

Despite longstanding recognition of thymic epithelial neoplasms, there is no official American Joint Committee on Cancer/ Union for International Cancer Control stage classification. This article summarizes proposals for classification of the T component of stage classification for use in the 8th edition of the tumor, node, metastasis classification for malignant tumors. This represents the output of the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group Staging and Prognostics Factor Committee, which assembled and analyzed a worldwide database of 10,808 patients with thymic malignancies from 105 sites. The committee proposes division of the T component into four categories, representing levels of invasion. T1 includes tumors localized to the thymus and anterior mediastinal fat, regardless of capsular invasion, up to and including infiltration through the mediastinal pleura. Invasion of the pericardium is designated as T2. T3 includes tumors with direct involvement of a group of mediastinal structures either singly or in combination: lung, brachiocephalic vein, superior vena cava, chest wall, and phrenic nerve. Invasion of more central structures constitutes T4: aorta and arch vessels, intrapericardial pulmonary artery, myocardium, trachea, and esophagus. Size did not emerge as a useful descriptor for stage classification. This classification of T categories, combined with a classification of N and M categories, provides a basis for a robust tumor, node, metastasis classification system for the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control stage classification

Post-traumatic stress disorder in children and adolescents one year after a super-cyclone in Orissa, India: exploring cross-cultural validity and vulnerability factors

BACKGROUND: It has been asserted that psychological responses to disasters in children and adolescents vary widely across cultures, but this has rarely been investigated. The objectives of the study were to clinically evaluate the construct of traumatic stress symptoms and disorder in children and adolescents after a super-cyclone in Orissa, India; to find out the prevalence at one year; compare the effect in high and low exposure areas and study the factors associated with it. METHODS: Clinical examination of children and adolescents (n = 447) was done, supplemented by a symptoms checklist based on International Classification of Mental and Behavioural Disorders, Diagnostic Criteria for Research and a semi-structured questionnaire for disaster related experiences. RESULTS: A majority of children had post-traumatic symptoms. Post-traumatic stress disorder (PTSD) was present in 30.6% (95% confidence interval: 26.4 to 34.9), and an additional 13.6% had sub-syndromal PTSD. Parents or teachers reported mental health concerns in 7.2% subjects, who were a minor proportion (12.8%) of subjects with any syndromal diagnosis (n = 196). Significantly more (43.7%) children in high exposure areas had PTSD than that (11.2%) in low exposure areas (p < 0.001). Depression was significantly associated with PTSD. Binary logistic regression analysis indicated that high exposure, lower educational level and middle socioeconomic status significantly predicted the outcome of PTSD. Extreme fear and perceived threat to life during the disaster, death in family, damage to home, or staying in shelters were not significantly associated with PTSD. CONCLUSION: Following natural disaster PTSD is a valid clinical construct in children and adolescents in Indian set up; and though highly prevalent it may be missed without clinical screening. Its manifestation and associated factors resembled those in other cultures