Holistic numerical calibration of the iMESA electrostatic analyzer.

A drifted Maxwellian velocity distribution is the most common model used to interpret the data from low-energy charged-particle instruments onboard spacecraft that are used to investigate the ambient plasma environment in the low Earth orbit (LEO). An original method is presented for determining the flow parameters (density, temperature, and flow energy) of such a distribution from the output of the integrated miniaturized electrostatic analyzer, which has been successfully flown on several LEO missions. Rather than attempting to deconvolve from the on-orbit data the analyzer's response to an ideal, monoenergetic input, numerical simulation is used to predict and parameterize the response of the device to an input distribution that includes an isotropic, non-zero temperature, yielding a straightforward method for extracting the flow parameters from the spacecraft data. The method is computationally simple enough to be incorporated into a robust algorithm suitable for rapid batch processing or real-time analysis of data.

The integrated miniaturized electrostatic analyzer: A space plasma environment sensor.

The integrated Miniaturized Electrostatic Analyzer (iMESA) was a satellite-based ionospheric sensor that operated on NASA's Space Test Program Satellite (STPSat-3) from December 2013 to July 2019. The instrument's scientific objective was to (1) measure the plasma density in low Earth orbit, (2) measure the plasma temperature in low Earth orbit, and (3) quantify the spacecraft potential with respect to the ambient plasma potential in the ionosphere. iMESA sampled the ionosphere every 10 s by measuring the ion current density through the ESA as a result of the motion of the spacecraft through the plasma. Current density spectra were transmitted to the ground where they were post-processed into ion density spectra and then analyzed numerically to determine the ion density, ion temperature, and spacecraft potential. This article discusses the instrument design and simulation, the determination of a geometric factor, and data processing procedures and evaluates the final data product with regard to the mission success criteria. The ion density and ion temperature captured by the iMESA instrument are on the same order and range as the values predicted in the literature. The spacecraft potential was also quantified. The conclusion after the evaluation of the instrument's data product is that the scientific mission is successful on all three points.

Implementation of ironXS: a study of the acceptability and feasibility of genetic screening for hereditary hemochromatosis in high schools.

Hereditary hemochromatosis (HH), most often due to HFE C282Y homozygosity, is an iron overload disorder that can result in severe morbidity including hepatic cirrhosis. Predisposition to HH is easily diagnosed and morbidity is preventable by maintaining normal body iron and thus calls have been made to introduce community screening. The current study has been designed to assess the acceptability and feasibility of HH screening in high schools. Students (mostly 15-16 years of age) watched a purpose-designed DVD for education about HH. Those with parental consent were then offered cheek-brush screening for C282Y. Students completed a questionnaire prior to screening. The program was offered to 9187 students at 32 schools and 3489 (38%) had screening. Nineteen C282Y homozygotes (1 in 183) and 376 heterozygotes (1 in 9.3) were identified. More than 90% of students answered each of five knowledge questions correctly. Eight homozygotes (42%) had elevated transferrin saturation, but only two (10.5%) had marginally elevated serum ferritin (SF). We have shown that genetic screening for HH can successfully be offered in the high school setting. Ongoing research in this study will answer questions about the impact of high school students learning that they are at risk of HH.

Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity.

Overexpression and/or activity of c-Src non-receptor tyrosine kinase is associated with progression of several human epithelial cancers including breast cancer. c-Src activity in 'pure' ductal carcinoma in situ (DCIS) was measured to assess whether this predicts recurrence and/or correlates with HER2 expression and other clinical parameters. Activated c-Src levels were evaluated in DCIS biopsies from 129 women, with median follow-up at 60 months. High levels of activated c-Src correlated with HER2 positivity, high tumour grade, comedo necrosis and elevated epithelial proliferation. In univariate analysis, high activated c-Src level associated with lower recurrence-free survival at 5 years (P=0.011). Thus, high c-Src activity may identify a subset of DCIS with high risk of recurrence or progression to invasive cancer where therapeutics targeting c-Src may benefit this patient subset.

Illudin S, the sole antiviral compound in mature fruiting bodies of Omphalotus illudens.

Crude extracts from the fruiting bodies of Omphalotus illudens displayed activity in the HSV-I/CV-1 antiviral assay. Bioactivity-guided isolation led to the known compound illudin S (1) as the sole antiviral component present in these extracts.

Oral creatine supplementation decreases plasma markers of adenine nucleotide degradation during a 1-h cycle test.

We investigated the effect of oral creatine supplementation (20 g d(-1) for 7 days) on metabolism during a 1-h cycling performance trial. Twenty endurance-trained cyclists participated in this double-blind placebo controlled study. Five days after familiarization with the exercise test, the subjects underwent a baseline muscle biopsy. Thereafter, a cannula was inserted into a forearm vein before performing the baseline maximal 1-h cycle (test 1 (T1)). Blood samples were drawn at regular intervals during exercise and recovery. After creatine (Cr) loading, the muscle biopsy, 1-h cycling test (test 2 (T2)) and blood sampling were repeated. Resting muscle total creatine (TCr), measured by high performance liquid chromatography, was increased (P < 0.001) in the creatine group from 123.0 +/- 3.8 - 159.8 +/- 7.9 mmol kg(-1) dry wt, but was unchanged in the placebo group (126.7 +/- 4.7 - 127.5 +/- 3.6 mmol kg(-1) dry wt). The extent of Cr loading was unrelated to baseline Cr levels (r=0.33, not significant). Supplementation did not significantly improve exercise performance (Cr group: 39.1 +/- 0.9 vs. 39.8 +/- 0.8 km and placebo group: 39.3 +/- 0.8 vs. 39.2 +/- 1.1 km) or change plasma lactate concentrations. Plasma concentrations of ammonia (NH(3)) (P < 0.05) and hypoxanthine (Hx) (P < 0.01) were lower in the Cr group from T1 to T2. Our results indicate that Cr supplementation alters the metabolic response during sustained high-intensity submaximal exercise. Plasma data suggest that nett intramuscular adenine nucleotide degradation may be decreased in the presence of enhanced intramuscular TCr concentration even during submaximal exercise.

Unusual multiple pilomatrixomata: case report and review of the literature.

Pilomatrixomata are rare, benign, calcifying cutaneous tumours of the hair matrix cells. They usually present in childhood with a pre-surgical diagnosis of sebaceous cyst, because of their size and appearance. The usual sites of occurrence are the scalp, head and neck. Treatment is usually surgical excision. We report a case of unusual, multiple, benign pilomatrixomata in an Indian adult. The plastic surgeon should be aware of the various guises of pilomatrixoma and be alert to the important, although rare, occurrence of malignancy.

Creating a research culture: what we can learn from residencies that are successful in research.

BACKGROUND AND OBJECTIVES: Despite a growing need for family practice to contribute to the national primary care research agenda, the specialty is ill-equipped to assume a more active role. Information about residency programs that are successful in research is a valuable resource for increasing family medicine's research capacity. METHODS: A three-stage investigation was completed in May 1996, consisting of 1) a telephone survey of family practice residency program directors, 2) a mail survey of recent graduates from relatively successful programs identified in stage 1, and 3) in-depth interviews with the program directors or research directors identified by combining data from the first two stages. RESULTS: Most residents in the programs included in stage 2 completed a research project (68.7%) and currently have an interest in practice-based research (57.2%). Residents from programs selected for the study's final stage were more likely to have published a research article (32% versus 20.3%) and to have completed a project while a resident (81% versus 60.1%) than those from the programs not selected. Virtually unanimous characteristics of successful programs include program director support of research, time for research, faculty involvement, a research curriculum, professional support, and opportunities for presenting research. CONCLUSIONS: Individual family practice residencies can be considered to be at one of three levels with respect to their level of research activity: 1) relatively undeveloped, 2) developing, or 3) relatively developed. Programs can expect successful results if they make research a priority, and means are needed for communicating successful strategies between programs.

Microvascular reconstruction of complex craniofacial defects.

Many large vault or skull base tumours are best treated by wide surgical excision and primary reconstruction using a microvascular free tissue transfer (free flap). We report 23 patients who were reconstructed using free flaps, eight having been previously treated surgically elsewhere and seven of whom had recurrent disease after radiotherapy. There was one flap failure and a local recurrence rate of 16% (3/19). The outcome at a mean follow-up period of 29 months, was 19 patients alive and four deaths.

African-American males and prostate cancer: assessing knowledge levels in the community.

Although the available evidence indicates that African-American males are at risk for developing prostate cancer, little is known about the level of awareness among African Americans about prostate cancer or how receptive they are to screening. This study examined the level of knowledge African-American males have about prostate cancer and the factors affecting knowledge levels. Face-to-face interviews were conducted among a sample of African-American males older than 25 years. All respondents were asked if they knew what prostate cancer was (N = 897), and those older than age 40 (N = 556) answered a series of seven questions related to prostate cancer. An index was created that reflected respondents level of knowledge about prostate cancer. Slightly more than 19% of the sample scored relatively high on the index related to prostate cancer knowledge, but 30% answered three or fewer questions correctly. Income, marital status, education, and type of insurance were significantly related to a respondent's level of knowledge. Having a regular physician and discussing prostate screening with a physician were both positively related to a respondent's level of understanding. This study indicates that African-American men do not have adequate knowledge about prostate cancer. Although many African Americans may be getting the prostate cancer message, educational efforts need to be strengthened to reach the less affluent and the less educated. These findings also raise questions about why more African-American men are not being screened and why more primary care physicians are not discussing prostate cancer with their African-American patients.

Current surgical treatment of Dupuytren's disease.

The practice of surgery for Dupuytren's contracture is changing. Most surgery can be carried out under regional or local anaesthesia on a day case basis. Although the commonest surgery performed is partial fasciectomy, there is more a polarisation developing with minimal surgery (e.g. segmental fasciectomy) for early disease and more aggressive surgery (dermofasciectomy) for advanced and recurrent disease.

Family practice residency program directors' views on research.

BACKGROUND AND OBJECTIVES: The culture of family practice training programs does little to convince residents that research is a worthwhile and important activity. The traditional dichotomy between research and clinical medicine persists today, despite an identified clinical mission for research. METHODS: As part of an effort to build the research capacity of family practice training programs, a telephone survey was administered in August 1995 to the program directors of all residency programs listed in the American Academy of Family Physicians 1995 Directory of Family Practice Residency Programs. The directors were asked about their program's research environment, features designed to promote research activity, and the level of resident research productivity. RESULTS: More than half (53.6%) of the program directors felt that their training program actively promotes research. Three out of four indicated that involving residents in research is a goal of their program. However, only four of 10 (40.8%) programs provide specific time for research, and family practice residents appear to be relatively inactive by conventional measures of research productivity. CONCLUSIONS: Research appears to be developing a limited role in family practice training programs. Resident research productivity remains relatively low and may be a result of residency programs not providing specific time for participating in research. However, the program directors' supportive attitudes may contribute to research and scholarly activity becoming an integral part of a family physician's training.

High postmortem concentrations of hypoxanthine and urate in the vitreous humor of infants are not confined to cases of sudden infant death syndrome.

OBJECTIVE: High concentrations of hypoxanthine and urate have been found in the blood of rats who died suddenly during induced respiratory alkalosis as well as in cases of sudden death in malignant hyperthermia-susceptible pigs challenged with halothane. The origin of these metabolites is the excessive hydrolysis of adenine nucleotides, which is associated with the production of free radicals. We wished to establish whether high levels of these compounds were also to be found in sudden infant death syndrome (SIDS) victims, compared with other causes of death. DESIGN: Vitreous humor samples were analysed for hypoxanthine and urate by high-performance liquid chromatography. SETTING: Forensic Laboratories, Salt River, Cape Town. PARTICIPANTS: Vitreous humor samples were collected from 91 infants presented for postmortem examination. MAIN OUTCOME AND RESULTS: From autopsy reports, cause of death was classified as: (i) SIDS (N = 50); (ii) acute sudden death (N = 5); and (iii) all other causes of death (N = 36). There were no differences in the hypoxanthine or urate levels of groups (i) and (iii) over the first 5 days of the postmortem period. Group (ii) levels were lower than those of both (i) and (iii). CONCLUSION: Adenine nucleotide hydrolysis is not only a feature of SIDS, and possibly results from antemortem hypoxia in most deaths. The lower concentrations found in cases of acute sudden death probably resulted only from postmortem hydrolysis of the nucleotides.

Structure--activity relationships of the didemnins.

Bioactivities of 42 didemnin congeners, either isolated from the marine tunicates Trididemnun solidum and Aplidium albicans or prepared synthetically and semisynthetically, have been compared. The growth inhibition of various murine and human tumor cells and plaque reduction of HSV-1 and VSV grown on cultured mammalian cells were used to assess cytotoxicity and antiviral activity. Biochemical assays for macromolecular synthesis (protein, DNA, and RNA) and enzyme inhibition (dihydrofolate reductase, thymidylate synthase, DNA polymerase, RNA polymerase, and topoisomerases I and II) were also performed to specify the mechanisms of action of each analogue. Immunosuppressive activity of the didemnins was determined using a mixed lymphocyte reaction (MLR) assay. These assays revealed that the native cyclic depsipeptide core is an essential structural requirement for most of the bioactivites of the didemnins, especially for cytotoxicities and antiviral activities. The linear side-chain portion of the peptide can be altered with a gain, in some cases, of bioactivities. In particular, dehydrodidemnin B, tested against several types of tumor cells and in in vivo studies in mice, as well as didemnin M, tested for the mixed lymphocyte reaction and graft vs host reaction in murine systems, showed remarkable gains in their in vitro and in vivo activities compared to didemnin B.

Skeletal muscle buffering capacity is higher in the superficial vastus than in the soleus of spontaneously running rats.

Skeletal muscle buffering capacity (beta mtitr) was determined in soleus (type I) and superficial vastus (type II) muscles of 16 Long-Evans rats with differing levels of spontaneous activity and in 11 sedentary control rats. beta mtitr was 24% higher (P < 0.001) in superficial vastus muscle than in soleus muscle (268 +/- 50 vs. 216 +/- 30 mumol H+ g muscle dry wt-1 pH unit-1) (mean +/- SD). There was no relationship between beta mtitr and mean weekly running distance amongst spontaneously running rats, nor was beta mtitr any greater in these rats than in a group of sedentary control rats. Protein to wet wt ratio was 31% higher (P < 0.0001) in the superficial vastus muscle when compared with soleus muscle (22.04 +/- 3.74 vs. 16.77 +/- 3.00 mg protein, 100 mg wet wt muscle-1), but there was no relationship between protein to wet wt ratio and running distance. Initial muscle homogenate pH (pHi) was lower in superficial vastus muscle compared with soleus muscle (6.36 +/- 0.25 vs. 6.63 +/- 0.16). Running rats had a significantly lower pHi in both soleus and superficial vastus than sedentary controls. There was an exponential relationship between weekly running distance and pHi in both the superficial vastus muscle (r = -0.86. P < 0.001) and the soleus muscle (r = -0.73, P < 0.01). Citrate synthase activity correlated with weekly running distance in superficial vastus muscle (r = 0.66, P < 0.01) but not in soleus muscle. The results confirm a higher beta mtitr in the type II superficial vastus muscle when compared with the predominantly type I soleus muscle. We suggest that this may be partly the result of a higher protein concentration in type II muscle. Future studies measuring beta mtitr in mixed muscle (e.g. human vastus lateralis) should report fibre type composition.

Adnexal adenocarcinoma of the upper lip.

A case of poorly differentiated adenocarcinoma of adnexal origin in the upper lip of a man aged 75 is reported which on presentation and initial biopsy was thought to be a salivary neoplasm. He had been aware of the lesion for 10 years but had sought treatment because of recent increase in size of the tumour. He subsequently developed bilateral metastases in cervical nodes. The histopathologic features and relationship of the tumour to the orbicularis oris muscle were consistent with a poorly differentiated adnexal adenocarcinoma of sweat-gland origin. Although carcinomas of skin adnexae are rare they should be considered in the differential diagnosis of tumours in the orofacial region.

The effects of carbohydrate loading on muscle glycogen content and cycling performance.

This study compared the effects of supplementing the normal diets of 8 endurance-trained cyclists with additional carbohydrate (CHO), in the form of potato starch, for 3 days on muscle glycogen utilization and performance during a 3-hr cycle ride. On two occasions prior to the trial, the subjects ingested in random order either their normal CHO intake of 6.15 +/- 0.23 g/kg body mass/day or a high-CHO diet of 10.52 +/- 0.57 g/kg body mass/day. The trial consisted of 2 hr of cycling at approximately 75% of VO2peak with five 60-s sprints at 100% VO2peak at 20-min intervals, followed by a 60-min performance ride. Increasing CHO intake by 72 +/- 9% for 3 days prior to the trial elevated preexercise muscle glycogen contents, improved power output, and extended the distance covered in 1 hr. Muscle glycogen contents were similar at the end of the 3-hr trial, indicating a greater utilization of glycogen when subjects were CHO loaded, which may have been responsible for their improved cycling performance.

Water ingestion does not improve 1-h cycling performance in moderate ambient temperatures.

Eight endurance-trained cyclists rode as far as possible in 1 h on a stationary cycle simulator in a moderate environment (20 degrees C, 60% relative humidity, 3 m.s-1 wind speed) while randomly receiving either no fluid (NF) or attempting to replace their approximate 1.71 sweat loss measured in a previous 1-h familiarisation performance ride at approximately 85% of peak oxygen uptake with artificially sweetened, coloured water (F). During F, the cyclists drank mean 1.49 (SEM 0.14) 1 of which mean 0.27 (SEM 0.08) 1 remained in the stomach at the end of exercise and mean 0.20 (SEM 0.05) 1 was urinated after the trial. Thus, only mean 1.02 (SEM 0.12) 1 of the ingested fluid was available to replace sweat losses during the 1-h performance ride. That fluid decreased the mean average heart rate from 166 (SEM 3) to 157 (SEM 5) beats.min-1 (P < 0.0001) and reduced the final mean serum [Na+] and osmolalities from 143 (SEM 0.6) to 139 (SEM 0.6) matom.l-1 (P < 0.005) and from 294 (SEM 1.7) to 290 (SEM 1.9) mosmol.l-1 (P = 0.05), respectively. Fluid ingestion did not significantly attenuate rises in plasma anti-diuretic hormone and angiotensin concentrations, or decrease the approximate-15% falls in estimated plasma volume in the F and NF trials. Nor did fluid ingestion significantly affect the approximate 1.71.h-1 sweat rates, the rises in rectal temperature (from 36.6 degrees to 38.3 degrees C) or the ratings of perceived exertion in the two trials.(ABSTRACT TRUNCATED AT 250 WORDS)