Fly-ear inspired micro-sensor for sound source localization in two dimensions.

Inspired by the hearing organ of the fly Ormia ochracea, a miniature sound localization sensor is developed, which can be used to pinpoint a sound source in two dimensions described by the azimuth and elevation angles. The sensor device employs an equilateral triangle configuration consisting of three mechanically coupled circular membranes whose oscillations are detected by a fiber-optic system. The experimental results indicate that significant amplification of the directional cues and directional sensitivity can be achieved with the fly-ear inspired sensor design. This work can provide a basis for the development of miniature sound localization sensors in two dimensions.

Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study.

BACKGROUND: The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12. METHODS: This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD). PRIMARY RESULTS: At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p's<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03). CONCLUSIONS: ABCD Study participants aged 9-10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort.

Natural orifice transesophageal mediastinoscopy and thoracoscopy.

BACKGROUND: Thoracoscopy and mediastinoscopy are common procedures with painful incisions and prominent scars. A natural orifice transesophageal endoscopic surgical (NOTES) approach could reduce pain, eliminate intercostal neuralgia, provide access to the posterior mediastinal compartment, and improve cosmesis. In addition NOTES esophageal access routes also have the potential to replace conventional thoracoscopic approaches for medial or hilar lesions. METHODS: Five healthy Yorkshire swine underwent nonsurvival natural orifice transesophageal mediastinoscopy and thoracoscopy under general anesthesia. An 8- to 9.8-mm video endoscope was introduced into the esophagus, and a 10-cm submucosal tunnel was created with blunt dissection. The endoscope then was passed through the muscular layers of the esophagus into the mediastinal space. The mediastinal compartment, pleura, lung, mediastinal lymph nodes, thoracic duct, vagus nerves, and exterior surface of the esophagus were identified. Mediastinal lymph node resection was easily accomplished. For thoracoscopy, a small incision was created through the pleura, and the endoscope was introduced into the thoracic cavity. The lung, chest wall, pleura, pericardium, and diaphragmatic surface were identified. Pleural biopsies were obtained with endoscopic forceps. The endoscope was withdrawn and the procedure terminated. RESULTS: Mediastinal and thoracic structures could be identified without difficulty via a transesophageal approach. Lymph node resection was easily accomplished. Pleural biopsy under direct visualization was feasible. Selective mainstem bronchus intubation and collapse of the ipsilateral lung facilitated thoracoscopy. In one animal, an inadvertent 4-mm lung incision resulted in a pneumothorax. This was decompressed with a small venting intercostal incision, and the remainder of the procedure was completed without difficulty. CONCLUSIONS: Transesophageal endoscopic mediastinoscopy, lymph node resection, thoracoscopy, and pleural biopsy are feasible and provide excellent visualization of mediastinal and intrathoracic structures. Survival studies will be needed to confirm the safety of this approach.

Leaders by example: Best practices and advice on establishing a state-of-the art surgical simulation center that optimizes available resources.

BACKGROUND: The role of simulation-based education continues to expand exponentially. To excel in this environment as a surgical simulation leader requires unique knowledge, skills, and abilities that are different from those used in traditional clinically-based education. METHODS: Leaders in surgical simulation were invited to participate as discussants in a pre-conference course offered by the Association for Surgical Education. Highlights from their discussions were recorded. RESULTS: Recommendations were provided on topics such as building a simulation team, preparing for accreditation requirements, what to ask for during early stages of development, identifying tools and resources needed to meet educational goals, expanding surgical simulation programming, and building educational curricula. CONCLUSION: These recommendations provide new leaders in simulation with a unique combination of up-to-date best practices in simulation-based education, as well as valuable advice gained from lessons learned from the personal experiences of national leaders in the field of surgical simulation and education.

Late lessons from early warnings: towards precaution and realism in research and policy.

This paper focuses on the evidentiary aspects of the precautionary principle. Three points are highlighted: (i) the difference between association and causation; (ii) how the strength of scientific evidence can be considered; and (iii) the reasons why regulatory regimes tend to err in the direction of false negatives rather than false positives. The point is made that because obtaining evidence of causation can take many decades of research, the precautionary principle can be invoked to justify action when evidence of causation is not available, but there is good scientific evidence of an association between exposures and impacts. It is argued that the appropriate level of proof is context dependent, as "appropriateness" is based on value judgements about the acceptability of the costs, about the distribution of the costs, and about the consequences of being wrong. A complementary approach to evaluating the strength of scientific evidence is to focus on the level of uncertainty. If decision makers are made aware of the limitations of the knowledge base, they can compensate by adopting measures aimed at providing early warnings of un-anticipated effects and mitigating their impacts. The point is made that it is often disregarded that the Bradford Hill criteria for evaluating evidence are asymmetrical, in that the applicability of a criterion increases the strength of evidence on the presence of an effect, but the inapplicability of a criterion does not increase the strength of evidence on the absence of an effect. The paper discusses the reason why there are so many examples of regulatory "false negatives" as opposed to "false positives". Two main reasons are put forward: (i) the methodological bias within the health and environmental sciences; and (ii) the dominance within decision-making of short term economic and political interests. Sixteen features of methods and culture in the environmental and health sciences are presented. Of these, only three features tend to generate "false positives". It is concluded that although the different features of scientific methods and culture produce robust science, they can lead to poor regulatory decisions on hazard prevention.

Reproductive senescence in female C57BL/6J mice: ovarian impairments and neuroendocrine impairments that are partially reversible and delayable by ovariectomy.

Ovarian and neuroendocrine impairments were examined before and after the age-correlated loss of estrous cycles in C57BL/6J female mice. The role of ovarian secretions in inducing neuroendocrine impairments before and after the loss of estrous cycles was also examined by determining neuroendocrine impairments after prolonged ovariectomy. Young (6-month-old) cycling, middle-aged (12-, 14-, and 16-month-old) cycling or acyclic, and old (18-month-old) acyclic mice were used. Ovarian impairments were assessed by grafting old ovaries into young hosts. Neuroendocrine impairments were assessed by grafting young ovaries into middle-aged and old hosts, ovariectomized either at grafting or 2 months before, and by inducing a LH surge in mice that had been ovariectomized for 4 days, 1 month, or 2 months. One group of 16-month-old and one group of 18-month-old mice were also ovariectomized at 6 months of age; these groups were used to examine the steroid-induced LH surge. The LH surge was induced by inserting sc a single priming estradiol (E2) implant, followed by two more (surge-inducing) implants 6 days later; 33 h after the second implantation, mice were decapitated (1800 h). The number of estrous cycles supported by middle-aged and old ovaries grafted into young hosts was reduced by more than 90% compared with that in young ovaries. The number of estrous cycles supported by middle-aged and old hosts given young ovarian grafts was reduced by 60% and 90%, respectively, compared with that in young hosts. Middle-aged and old hosts also had progressively longer estrous cycles than young hosts. Levels of the E2-induced LH surge in middle-aged and old mice were also reduced by 60% and 90%, respectively, compared with levels in young mice. In old acyclic mice, ovariectomy for 2 months partially reversed impairments in the LH surge and partially restored the ability to support cycles with young grafts; these functions, normally 90% impaired in old mice, were only 60% impaired after prolonged ovariectomy. Moreover, ovariectomy 2 months before grafting in old hosts resulted in shorter estrous cycles and 60% fewer pituitary adenomas. In middle-aged cycling mice, ovariectomy for 2 months did not affect impairments in the LH surge or in the ability to support estrous cycles with young grafts; these functions remained 60% impaired in middle-aged mice ovariectomized for 2 months. If mice were ovariectomized when young, the age-correlated impairments of the E2-induced LH surge at 16 months were largely prevented.(ABSTRACT TRUNCATED AT 400 WORDS)

The regulation of luteinizing hormone and prolactin in C57BL/6J mice: effects of estradiol implant size, duration of ovariectomy, and aging.

The induction of a LH surge by estradiol (E2) implants was characterized in ovariectomized C57BL/6J mice. Various times after ovariectomy mice were given a priming E2 implant, followed by an LH surge-inducing E2 implant, and were sampled 30 h later at darkness. The magnitude of the E2-induced LH surge was influenced by the postovariectomy interval, sizes of the implants, and age. Mice ovariectomized for 30-60 days before E2 implantation displayed larger surges than those ovariectomized for 4 days. Priming implants yielding 10 pg E2/ml plasma permitted the subsequent induction of vigorous LH surges, whereas no LH surges were observed with slightly larger priming implants that yielded 15 pg E2/ml. The size of the surge-inducing implant was correlated with the size of the subsequent LH surge. However, regardless of implant size, aging mice (8 vs. 13 months old) had smaller LH surges. Sequential daily LH surges were not observed under any conditions, suggesting that mice differ from rats and hamsters in their regulation of LH by E2. Plasma PRL was slightly elevated in the afternoon just before the LH surge, but returned to basal levels during the LH surge, indicating an uncoupling of the LH and PRL surges. The two-stage E2 implantation protocol for inducing LH surges by physiological levels of E2 allows more detailed examination of the priming vs. surge-inducing effects of E2.

Cytomegalovirus infection complicating renal transplantation and its relationship to acute transplant glomerulopathy.

The incidence of cytomegalovirus (CMV) infection was established, using laboratory criteria, in 298 patients receiving 362 renal allografts (164/298 = 55%). The incidence of CMV infection did not differ between azathioprine/prednisolone-treated and cyclosporine-treated patients (55% vs. 57% NS). The use of antithymocyte globulin (ATG) increased the incidence of CMV infection (78% vs. 51%: P less than 0.01). Donor and recipient CMV status, known for 116 allografts, did not correlate with the incidence of CMV infection (recipient CMV-positive = 50%; recipient CMV-negative = 54%: NS). CMV infection was responsible for 8 patients' deaths (2.7% mortality). Thirty-three patients with acute transplant glomerulopathy were identified (11%). There was no correlation between acute transplant glomerulopathy and CMV infection. Glomerulopathy was associated with poor graft survival (22/33 patients with a graft survival of less than 6 months). Thus CMV infection, although a common complication of renal transplantation with significant morbidity and mortality, is not closely associated with acute transplant glomerulopathy. Further, the lack of correlation of donor-recipient CMV serologic status with graft outcome limits the usefulness of pretransplantation donor screening.

Immunohistological analysis of serial biopsies taken during human renal allograft rejection. Changing profile of infiltrating cells and activation of the coagulation system.

This immunohistological study investigated two aspects of the mechanisms underlying human renal allograft rejection. First, because rejection is a dynamic, complex process, we sought to delineate any changes in the types of cells mediating graft destruction by evaluating the cellular infiltrates in sequential renal biopsies from 14 patients with rejection. Second, because macrophage accumulation and fibrin deposition are major features of kidney rejection, the membrane characteristics of intragraft macrophages were analyzed to determine whether these cells could indeed cause the fibrin deposition frequently observed. Thirty-six biopsies, performed for assessment of renal failure posttransplantation (post-Tx), were studied using a panel of monoclonal antibodies and a 4-layer immunoperoxidase technique. Biopsies were divided into 3 groups depending upon the time post-Tx. Comparison of biopsies taken on days 2-3 post-Tx with those taken either at days 10-12, or later than 30 days, showed similar proportions of T cells, T cell subsets, B cells and macrophages. By contrast, the proportion of natural killer (NK) cells was significantly increased at days 2-3 (P less than .01), and the proportion of activated T cells bearing interleukin-2 receptors was significantly increased at days 10-12 (P less than .01). Granulocytes were restricted to biopsies that displayed areas of infarction, regardless of the time at which this occurred. In addition, various proportions of intragraft macrophages exhibited the membrane phenotype of activated macrophages, as a result of their expression of the procoagulant molecule termed human-tissue-factor--related antigen (HTF:RAg). The proportion of graft macrophages exhibiting HTF:RAg was significantly increased in biopsies on days 10-12 (P less than .05) compared with biopsies on days 3-4, and remained elevated thereafter. Interstitial and perivascular collections of HTF:RAg+ macrophages were closely associated with fibrin deposits and, in two cases, mononuclear cells harvested from rejected grafts were shown to contain significant procoagulant activity in vitro. These studies demonstrate a major temporal variation in the types of cells contributing to human kidney rejection.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of ribose on thallium-201 myocardial redistribution.

Myocardial 201Tl redistribution after transient ischemia may be too slow to allow identification of a reversible myocardial defect within the routine 201Tl imaging period. To determine whether 201Tl redistribution could be affected by a metabolic intervention, intravenous ribose was administered postischemia. Seventeen domestic swine were subjected to a 10-min ischemic period followed by either a 30-min i.v. ribose (n = 8) or saline (n = 9) infusion. Thallium-201 was injected during ischemia and myocardial 201Tl activity was continuously monitored in ischemic and nonischemic regions with miniature CdTe radiation detection probes. Coronary flow in the ischemic region was reduced to 25% of that in the nonischemic regions in both saline and ribose groups. The 201Tl time-activity curves demonstrated a significant enhancement of % 201Tl redistribution in the ribose-treated animals at the end of ribose infusion: Ribose (48 +/- 11%), Saline (20 +/- 4%), p less than 0.05. Alteration of 201Tl kinetics by ribose may permit earlier recognition of 201Tl myocardial redistribution after transient ischemia.

Prognostic significance of exercise-induced left ventricular dysfunction in chronic aortic regurgitation.

Twenty-three patients with hemodynamically significant aortic regurgitation (AR) underwent gated equilibrium radionuclide angiography to assess rest and exercise left ventricular ejection fraction (LVEF) before and after aortic valve replacement. Preoperatively, LVEF decreased from 54 +/- 3% at rest to 45 +/- 3% during exercise (p less than 0.001). Two patients died at operation. Postoperatively, after 5.7 +/- 1.6 months, LVEF was 62 +/- 5% at rest and 60 +/- 4% during exercise (difference not significant). Exercise LVEF improved significantly postoperatively (p less than 0.01). The patients were followed for a mean of 30 months (range 1 to 56), after valve replacement and during this period, 13 patients were in functional class I, 5 patients were in class II and 2 patients were in class III. One late death occurred and was unrelated to myocardial failure. Thus, in most patients with AR, exercise LVEF improves after aortic valve replacement. A preoperative decrease in LVEF during exercise in patients with significant AR does not predict a poor postoperative outcome.

Traumatic subarachnoid haemorrhage: an alternative source.

Traumatic subarachnoid haemorrhage is known on many occasions to result from a blow on the neck rupturing the vertebral artery within the cervical spine. On some occasions, however, no such damage to the artery in the neck can be found to account for the haemorrhage. Some cases are described in which the source of haemorrhage was rupture of the vertebral artery within the skull close to the basilar artery. The reason why rupture should occur at this site is discussed.

Estimation of phenolic conjugation by colonic mucosa.

Conjugation of phenol by the colonic mucosa was assessed in vivo using dialysis tubing containing 1.5 ml of 1 mmol/l acetaminophen (paracetamol) and 10 mmol/l butyrate. These were allowed to equilibrate in the rectum for one hour. The glucuronidated and sulphated conjugates of acetaminophen were measured by high pressure liquid chromatography and bicarbonate concentrations by gas analysis. In 21 subjects without colonic disease sulphate conjugation was observed in all cases, with a mean (SE) of 3.86 (0.66) nmol/hour, while glucuronide conjugation was found in seven of 21 cases. Mean (SE) bicarbonate output of 42.9 (3.9) mumol/hour (n = 21) indicated healthy colonic mucosal metabolism and phenolic sulphation in dialysate and agreed with published sulphation rates obtained with cultured cells of colonic epithelium. Acetaminophen sulphation suggests that the colonic mucosa has an important role in the conjugation of phenols, and the method reported here would be useful in assessing the detoxification capacity of the colonic mucosa in diseases of the rectal mucosa.

Collagenous colitis: jejunal and colorectal pathology.

AIMS: To determine: (1) whether there is an association between collagenous colitis and coeliac disease or lymphocytic colitis; (2) the distribution of lymphocyte subsets and macrophages in the lamina propria and surface epithelial layer in collagenous colitis; and (3) the colorectal distribution of the disease and whether a mucosal biopsy specimen, using a flexible sigmoidoscope, is sufficient to diagnose it. METHODS: The clinical data and colorectal biopsy specimens from 38 patients with collagenous colitis were studied. In 10, small bowel biopsy specimens were also available for review. Immunostaining of the mucosal lymphoid infiltrate with a panel of relevant antibodies was carried out on formalin fixed tissue in seven cases; in three the phenotyping was performed on fresh biopsy specimens separately frozen or fixed in B5 solution. RESULTS: Coeliac disease was found in four out of the 10 patients with collagenous colitis who had had a small bowel biopsy, in contrast to the prevalence of the disease in Australia of 1 in 3000. Collagenous colitis did not respond to gluten withdrawal. Five of 29 (17%) of the patients had a mixed pattern of lymphocytic and collagenous colitis. Immunostaining of the lymphoid infiltrate showed that the striking increase in intraepithelial lymphocytes in collagenous colitis was due to an influx of CD8 positive cells. The occurrence and severity of collagenous colitis along the large bowel were independent of the anatomical site, and in more than 90% of cases biopsy specimens from the sigmoid colon or rectum were diagnostic. CONCLUSIONS: There is a very high incidence of coeliac disease among patients with collagenous colitis so that jejunal biopsy should be an essential part of their investigations, especially if symptoms persist. However, only a minority showed a mixed pattern of lymphocytic and collagenous colitis. The intraepithelial lymphocytes in collagenous colitis are CD8 positive cells. Collagenous colitis can be diagnosed from rectal or sigmoid colon biopsy specimens in more than 90% of cases.

Effect of L-leucine on oral melphalan kinetics in patients.

Melphalan uptake in the intestine has recently been shown to be an energy-dependent process which is affected by metabolic inhibitors. It is therefore theoretically possible that amino acids in food could reduce melphalan absorption by competing for uptake at the sites of absorption in the intestine. Since L-leucine has been shown to be the most potent inhibitor of melphalan transport into cells in vitro, this amino acid was chosen for the present study in patients. Oral melphalan (4.5 +/- 0.5 mg/m2) was given to ten fasting patients with and without a 2-g oral dose of L-leucine on separate randomized occasions at least 1 week apart. Melphalan plasma levels were measured by high-performance liquid chromatography (HPLC) for 5-h after dosing. L-Leucine plasma levels were measured by HPLC before and at 1 h after dosing. The area under the curve for melphalan was lower in seven of the patients after L-leucine. Plasma L-leucine levels 1 h after melphalan administration were 15.4 +/- 3.7 micrograms/ml fasting and 35.4 +/- 5.2 micrograms/ml after L-leucine. The results indicate that L-leucine can reduce plasma melphalan levels in some patients, probably through a reduction in absorption of the drug from the gastrointestinal tract. However, the effect, like that of food, is highly variable.

The teaching of cultural issues in U.S. and Canadian medical schools.

PURPOSE: Despite the importance of culture in health care and the rapid growth of ethnic diversity in the United States and Canada, little is known about the teaching of cultural issues in medical schools. The study goals, therefore, were to determine the number of U.S. and Canadian medical schools that have courses on cultural issues, and to examine the format, content, and timing of those courses. METHOD: The authors contacted the deans of students and/ or directors of courses on cultural issues at all 126 U.S. and all 16 Canadian medical schools. Using a cross-sectional telephone survey, they asked whether each school had a course on cultural sensitivity or multicultural issues and, if so, whether it was separate or contained within a larger course, when in the curriculum the course was taught, and which ethnic groups the course addressed. RESULTS: The response rates were 94% for both U.S. (118) and Canadian (15) schools. Very few schools (U.S. = 8%; and Canada = 0%) had separate courses specifically addressing cultural issues. Schools in both countries usually addressed cultural issues in one to three lectures as part of larger, mostly preclinical courses. Significantly more Canadian than U.S. schools provided no instruction on cultural issues (27% versus 8%; p = .04). Few schools taught about the specific cultural issues of the largest minority groups in their geographic areas: only 28% and 26% of U.S. schools taught about African American and Latino issues, respectively, and only two thirds of Canadian schools taught about either Asian or Native Canadian issues. Only 35% of U.S. schools addressed the cultural issues of the largest minority groups in their particular states. CONCLUSIONS: Most U.S. and Canadian medical schools provide inadequate instruction about cultural issues, especially the specific cultural aspects of large minority groups.

Benign vaginal rhabdomyoma.

A case of benign polypoid vaginal rhabdomyoma occurring in a 52-year-old female is described. The characteristic histological features were interlacing bands of striated muscle cells with prominent cross and longitudinal striations, with surrounding loose collagenous stroma, within which were many dilated vascular spaces. Electron microscopy confirmed the striated muscle origin of these cells. The pathogenesis is possibly a localized area of abnormal mesenchymal differentiation.

The pathological assessment of ovarian neoplasms. IV: The sex cord-stromal tumours.

All neoplasms of the ovary encountered in a 25-yr study period at the King George V Memorial Hospital were classified according to the World Health Organisation (WHO) Histological Classification of Ovarian Tumours. Of just less than 1700 tumours, 168 fell into the category designated as sex cord-stromal tumours, this report analysing their major clinical and pathological correlates. A detailed histological assessment is then presented, including 4 cases of the recently separated subcategory of sclerosing stromal tumour of the ovary.

Urine hydroxyproline: a potential error in quantification and a proposed procedure for its measurement.

A modification of the colorimetric method of Bergman and Loxley for the measurement of urinary hydroxyproline using external aqueous hydroxyproline standards instead of individual internal standards is described. We show that this modification leads to an underestimation (average 32%) of hydroxyproline because suppression of colour development occurs in urine samples but not in aqueous standards. Use of an internal standard for each urine test corrects for this suppression. Recovery of hydroxyproline (250 mumol/L) added to 12 patient urine samples averaged 99% and the overall imprecision for the assay was then less than 5%. Modifications to the original hydrolysis and colour development procedures allow linearity to 1500 mumol/L. Details of our procedure are given.

A fluffy white traveller: imported Coccidiodes immitis infection in an Australian tourist.

Pulmonary coccidioidomycosis is a rare cause of pulmonary nodules and respiratory infection in travellers to endemic areas. An Australian tourist suffered an acute respiratory illness while on holiday in Mexico. She subsequently developed erythema nodosum and was noted to have a left pulmonary nodule on chest X-ray after return to Australia. The diagnosis of Coccidioides immitis infection was established by histology and culture of the resected lung lesion. The patient made an uneventful recovery and received one month of therapy with ketoconazole. Culture of the fungus took place under controlled Class 3 conditions. An unusual fungal infection in Australia, coccidioidomycosis poses special risks to staff of microbiology laboratories.