Aggregation of Markov flows I: theory.

A Markov flow is a stationary measure, with the associated flows and mean first passage times, for a continuous-time regular jump homogeneous semi-Markov process on a discrete state space. Nodes in the state space can be eliminated to produce a smaller Markov flow which is a factor of the original one. Some improvements to the elimination methods of Wales are given. The main contribution of the paper is to present an alternative, namely a method to aggregate groups of nodes to produce a factor. The method can be iterated to make hierarchical aggregation schemes. The potential benefits are efficient computation, including recomputation to take into account local changes, and insights into the macroscopic behaviour.This article is part of the theme issue 'Hilbert's sixth problem'.

Advanced flow MRI: emerging techniques and applications.

Magnetic resonance imaging (MRI) techniques provide non-invasive and non-ionising methods for the highly accurate anatomical depiction of the heart and vessels throughout the cardiac cycle. In addition, the intrinsic sensitivity of MRI to motion offers the unique ability to acquire spatially registered blood flow simultaneously with the morphological data, within a single measurement. In clinical routine, flow MRI is typically accomplished using methods that resolve two spatial dimensions in individual planes and encode the time-resolved velocity in one principal direction, typically oriented perpendicular to the two-dimensional (2D) section. This review describes recently developed advanced MRI flow techniques, which allow for more comprehensive evaluation of blood flow characteristics, such as real-time flow imaging, 2D multiple-venc phase contrast MRI, four-dimensional (4D) flow MRI, quantification of complex haemodynamic properties, and highly accelerated flow imaging. Emerging techniques and novel applications are explored. In addition, applications of these new techniques for the improved evaluation of cardiovascular (aorta, pulmonary arteries, congenital heart disease, atrial fibrillation, coronary arteries) as well as cerebrovascular disease (intra-cranial arteries and veins) are presented.

The DRD2 TaqI-B polymorphism and its relationship to smoking abstinence and withdrawal symptoms.

The dopamine receptor D2 (DRD2) gene has polymorphisms that have been linked to regulation of the dopamine system and to an increased prevalence of smoking. The present study examined the relationship of the DRD2 TaqI-A and -B polymorphisms with short-term clinical outcome (abstinence and withdrawal symptoms), collected from daily (14 pre-quit and 42 post-quit) diary data among smokers (n=116) treated with the nicotine patch plus either venlafaxine or placebo. The results showed that B1/B1 or B1/B2 smokers were slightly less likely to be abstinent on a given day than those homozygous for the TaqI-B2 allele. Significant DRD2 TaqI-B x time interactions were found for several of the withdrawal scales, indicating that those smokers with the B1/B1 or B1/B2 genotypes tended to report more symptoms over time compared to those with the B2/B2 genotype. No interactions or main effects were found for the DRD2 TaqI-A polymorphism. The findings demonstrate that smokers homozygous for the TaqI-B2 allele experience progressive improvement in self-reported withdrawal symptoms while smokers with the TaqI-B1 allele showing little change.

Healthcare providers' sun-protection promotion and at-risk clients' skin-cancer-prevention outcomes.

BACKGROUND: This study aims to determine whether healthcare providers' (HCPs') communication dealing with sun-protection (i.e., counseling) is associated with clients' skin-cancer-related prevention practices, detection self-efficacy, and knowledge. METHODS: Secondary analysis of two surveys of 1,469 randomly sampled farmers and soccer participants from southeast and coastal Georgia. RESULTS: Farmers and soccer participants who report ever having been counseled by a HCP about how to protect their skin from the sun report being more likely to wear sunscreen (P < 0.05), get clinical exams of their skin (P < 0.001), be certain that they can recognize unhealthy changes in their skin (P < 0.001), be certain that they know how to perform a skin exam (P < 0.001), and be knowledgeable about skin cancer prevention (P < 0.05 and P < 0.001, respectively); soccer participants are additionally more likely to wear protective headgear (P < 0.05) and perform monthly self-exams of their skin (P < 0.001). All analyses incorporated three control variables: participants' prior history of skin cancer, age, and non-HCP-derived skin-cancer awareness. CONCLUSIONS: Findings suggest that HCPs' counseling can positively shape skin-cancer-related prevention practices, detection self-efficacy, and knowledge. Additional research is needed on HCPs' actual communication about skin cancer and sun protection and its influence on client outcomes.

Cell-cell interactions influence resistance and survival of Salmonella serotype Typhimurium to environmental stress.

AIMS: The aim of this work was to study the effects of prolonged nutrient stress on survival, cell interactions and resistance to inimical processes in Salmonella serotype Typhimurium. METHODS AND RESULTS: Salmonella Typhimurium cells were subjected to prolonged incubation in the stationary phase of growth and the properties of starved cells (old) were investigated with reference to those of exponentially-growing cells (young). Competition experiments between old and young cells revealed cell-cell interactions that influenced stationary phase survival and response of the bacterium to heat stress. During prolonged incubation of cells, cycles of resistance and sensitivity to heat stress were identified. Competition experiments between old and young cells revealed that the resistance of young cells to heat increased to levels more like those of stationary phase cells than growing cells. The presence of old cells influenced the phenotype of young cells, possibly by means of cell-cell interactions. There was no evidence for the involvement of any extracellularly-produced factors in this phenomenon, but a requirement that the old competitor cells be viable could be demonstrated. CONCLUSIONS: It is proposed that the complex interactions within stationary phase cultures of Salm. Typhimurium may be due to cycles of mutation in concert with an as yet undefined interaction between old cells and growing ones. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides evidence for active and diverse responses to nutrient stress within populations of Salm. Typhimurium that promote survival and that may be important for the success of this bacterium as a pathogen.

Closing medical encounters: two physician practices and their implications for the expression of patients' unstated concerns.

When patients visit primary-care physicians, they frequently have more than one concern. Patients' first concerns are solicited by physicians at the beginnings of encounters. A challenge to health care is how to get patients' additional concerns raised as topics of discussion. If patients' additional concerns are addressed, it tends to occur at the end of encounters. Using the methodology of conversation analysis, this article identifies and describes the interactional organization of two physician-initiated communication practices that are used to negotiate the closure of the business of encounters and a transition into the activity of closing encounters themselves. These practices have different implications for the topicalization of patients' additional concerns.

Women's health problems in soap operas: a content analysis.

A content analysis of women's health problems in network daytime serials is reported. Results indicate a preponderance of such problems as substance abuse, falls resulting in death or injury, comas or unconsciousness, mental health concerns (most notably represented by amnesia and multiple personality), concerns about AIDS, automobile accidents, being drugged, fainting, pregnancy problems, and violent acts resulting in harm. Such concerns as breast and cervical cancer and heart disease are less frequently portrayed.

The time course of emotional and attentional modulation of the startle eyeblink reflex during imagery.

Two studies were conducted to examine the time course of attentional and emotional processing using the startle eyeblink reflex. Forty-eight participants listened to a series of 1500-ms tones that occurred every 6 s. The tones signaled participants to generate emotional images that were positive or negative in valence and high or low in arousal. Auditory startle probes occurred 120 ms, 1400 ms, or 4000 ms after tone onset. Startle inhibition was seen 120 ms after tone onset and startle facilitation was found at 1400 ms, compared to startles elicited 4000 ms after tone onset. Startle inhibition was greater at 120 ms when the tone signaled imagery, indicating an attentional effect. A second experiment found that this effect was not caused by the comparative rarity of the tones signaling imagery. Startle magnitude was also smaller at 1400 ms when the tone signaled imagery compared to no-imagery tones. The type of imagery did not modulate the startle response 120 ms after tone onset, but negative valence imagery enhanced startle magnitude at 1400 ms and 4000 ms after tone onset, and high arousal also enhanced startle magnitude at 4000 ms. Thus, attention and emotion followed different time courses in affecting the startle reflex response during imagery.

Iodine insufficiency and neonatal hyperthyrotropinaemia in Hong Kong.

OBJECTIVES: 23% of the neonatal hypothyroidism in Hong Kong is transient. The present study aims to evaluate iodine excretion in healthy pregnant women in Hong Kong and to determine whether iodine insufficiency may occur in the local population to account for the type of neonatal thyroid dysfunction seen in our screening programme. SUBJECTS: Pilot screening of urinary iodine excretion was determined in 253 healthy pregnant women between 32 and 36 weeks gestation. Fetal and maternal thyroid function in relation to urinary iodine excretion was evaluated in another 55 pregnant women who had given birth to infants with cord blood TSH > or = 16 mIU/I (95th percentile of the cord blood TSH screening programme) and the results were compared to a control group of 160 healthy women whose infants had cord blood TSH < 16 mIU/I. RESULTS: Using a cut-off value of 0.79 mumol/l, a level as defined by WHO as iodine deficiency, we found that 35.8% of the pregnant women had urinary iodine concentrations below this cut off value. We demonstrated that the existence of borderline iodine supply affected the maternal and fetal thyroid function as evidenced by (i) a negative correlation between maternal TSH and urinary iodine concentration, (ii) higher cord blood TSH in those infants whose mothers had a low urinary iodine concentration as compared to those in whose mothers it was normal, (iii) women who had given birth to infants with cord blood TSH > or = 16 mIU/I had lower urinary iodine concentrations and serum fT4 levels as compared to mothers who had given birth to infants with normal cord TSH levels, and their offspring also had higher cord blood thyroglobulin levels. CONCLUSION: Although Hong Kong is not a goitrous area, borderline iodine deficiency exists. Iodization of salt in our community could obviate the necessity for iodine supplements in pregnant women and other at-risk groups.

Transient kinetics of substrate binding to Na+/K(+)-ATPase measured by fluorescence quenching.

This paper examines the transient kinetics of substrate binding to the Na+/K(+)-ATPase labelled with iodoacetamidofluorescein (IAF) using fluorescence quenching by trinitrophenyl-ATP (TNP-ATP). Earlier work (E.H. Hellen, P.R. Pratap, 1996, Fluorescence quenching of IAF-Na+/K(+)-ATPase via energy transfer to TNP-labelled nucleotide, Proceedings of the VIIIth International Conference on the Na+/K(+)-ATPase, in press) has shown that TNP-nucleotide binds to specific sites (from which unlabelled nucleotide can displace it) and nonspecific sites (from which unlabelled nucleotide cannot displace it). Under stopped-flow conditions, quenching of IAF-enzyme fluorescence was well described by a stretched exponential (F(t) = F infinity + delta F exp[-Bt alpha]). Physically, this function may be interpreted in terms of its inverse Laplace transform phi (k), which describes a distribution of rate-constants; alpha reflects the width of this distribution. As TNP-ATP concentration increased, alpha decreased, reflecting TNP-ATP binding to sites with higher energy barriers. alpha decreased by about the same amount with increasing [TNP-ATP] in the presence of saturating ATP, indicating that the distribution of rate-constants is largely associated with the nonspecific binding sites. However, alpha was significantly less than 1 for ATP-induced fluorescence recovery in the presence of TNP-ATP, indicating that rate-constants associated with specific binding site are also distributed. The distribution of rate-constants for binding to the specific site indicates a distribution in the energy of the transition state for substrate binding. These results suggest that the specific binding site (in either the empty or the full state) may exist in a series of conformations separated by small energy barriers. However, the energy barriers for binding associated with these conformations are significantly distributed.

Kinetics of conformational changes associated with potassium binding to and release from Na+/K(+)-ATPase.

The Na+/K(+)-ATPase functions in cells to couple energy from the hydrolysis of ATP to the transport Na+ out and K+ in. The fluorescent probe IAF (iodoacetamidofluorescein) covalently binds to this enzyme, reporting conformational changes without inhibiting enzyme activity. This paper describes experiments using dog kidney enzyme labeled with IAF to examine kinetics of conformational changes resulting from added Na+ and K+, measured in terms of steady-state and stopped-flow fluorescence changes. Kinetics of these fluorescence changes were examined as a function of temperature from two initial conditions: (a) enzyme in the high-fluorescence form (E(high)) was rapidly mixed with varying [K+]; and (b) enzyme in the low-fluorescence form (E(low)) was rapidly mixed with varying [ATP]. These experiments showed: (1) The rate constant for the fluorescence change from E(high) to E(low) was much larger than that for the opposite transition, E(low) to E(high); (2) the apparent free energy of activation (Ea(app)) for the two transitions were different (as estimated from Arrhenius plots); (3) under steady-state conditions, IAF fluorescence did not change when ATP was added to E(low)(K+) in the absence of Na+; (4) the apparent free energy of activation was independent of [K+] for the E(high) to E(low) transition (at 16.4 kcal/mol) but increased with [ATP] for the E(low) to E(high) transition; (5) Ea(app) for the E(low) to E(high) transition with 1 mM ATP was approximately the same as that in the absence of ATP (34 kcal/mol). These results can be interpreted as: (i) in the transition from E(low) to E(high), IAF reported a conformational change that occurred after K+ release to the intracellular side and which is involved in Na+ binding; (ii) Ea(app) increased with [ATP], while increasing the entropy of the transition state. Thus, ATP appeared to destabilize the enzyme during the transition from E(low) to E(high).

Existence of iodine deficiency in Hong Kong--a coastal city in southern China.

OBJECTIVE: Iodine deficiency is a serious public health problem worldwide which is associated with mental retardation and cretinism. In view of a high incidence of transient neonatal hypothyroidism and a relatively high mean cord blood thyrotropin (TSH) concentration, a pilot study was carried out to analyse the urine iodine excretion in Hong Kong, a coastal city in the southern part of China. DESIGN: Early morning urine was collected from healthy volunteers including children (n = 104), adults (n = 112) and elderly subjects (n = 349). A semi-quantitative questionnaire survey on the pattern of food intake was conducted in the adults and elderly. RESULTS: 45.3% of the children, 51.7% of the adults and 55.3% of the elderly had urine iodine concentration below the criteria for iodine sufficiency (< 0.79 mumol/l). Iodine content in the drinking water and salt was low. A dietary survey revealed that seafood was not commonly consumed. 50-80% of the subjects never consumed high-iodine containing food such as seaweed, kelp or laver, and only 50% consumed seawater fish daily. CONCLUSION: We confirmed that although Hong Kong is a non-goitrous area, iodine insufficiency exists. It is unsafe to assume that iodine deficiency does not exist in coastal urban areas.

The Howard University Hospital Transplant and Dialysis Support Group: twenty years and going strong.

This article discusses group therapy as part of a multidisciplinary approach to the management of the various psychological and physical rehabilitation concerns posed by kidney and liver transplant candidates and recipients at Howard University Hospital in Washington, DC. The group's history, format, intervention foci, and roles of clinicians and patients attending the group are described and evaluated. Given the relative paucity of research literature in this area, the authors offer recommendations for empirical evaluation of the benefits of multidisciplinary group psychotherapy in ameliorating physical and emotional suffering and prolonging life among transplant patients.

Rapid kinetic analyses of the Na+/K(+)-ATPase distinguish among different criteria for conformational change.

The Na+/K(+)-ATPase couples the hydrolysis of ATP to the transport of Na+ and K+ via a phosphorylated intermediate and conformational changes. In order to identify these conformational changes, we have probed the sequence of steps from EP(3Na+ in) to EP + 3Na+ out with three fluorescent probes (IAF: 5-iodoacetamidofluorescein; BIPM: N-[p-(2-benzimidazolyl)phenyl]maleimide; and RH421) and the sensitivity of their fluorescence change to oligomycin and divalent cations (Ca2+ and Mn2+). The magnitude (% delta F) and rate constant (k(obs)) of ATP-induced fluorescence changes were measured on a fluorescence stopped-flow apparatus, and yielded the following results. (a) With RH421, k(obs) and % delta F varied with [Na+] (maximal k(obs) = 100 s-1, K1/2 = 6 mM; % delta Fmax = 6%, K1/2 = 1 mM); these values are comparable to those previously reported using IAF-labeled enzyme (Pratap, P.R., Robinson, J.D. and Steinberg, M.I. (1991) Biochim. Biophys. Acta 1069, 288-298). (b) With BIPM-labeled enzyme k(obs) did not vary with [Na+] over the range tested, and was twice as high as the maximum k(obs) for RH421. (c) Treatment with oligomycin reduced k(obs) for all three probes to about the same level (approximately 1-2 s-1) while % delta Fmax was largely unaffected. (d) Replacing Mg2+ with Ca2+ had similar effects to treatment with oligomycin. (e) RH421 fluorescence change was completely abolished in the presence of oligomycin and Ca2+. (f) Replacing Mg2+ with Mn2+ decreased IAF fluorescence, i.e., put the enzyme in an E2-like form, reduced k(obs), and rendered oligomycin less effective in reducing k(obs). From these results, we conclude: (a) the release of the second/third Na+ is the rate-limiting step for the conformational change measured by IAF and charge transfer measured with RH421; (b) BIPM indicates an earlier step, either the deocclusion of Na+ and/or the release of the first Na+; (c) oligomycin blocks Na+ deocclusion, and this step is sensitive to the divalent cation used to activate enzyme phosphorylation; and (d) Ca2+ slows the step reported by IAF as well. These experiments indicate that a simple model with two conformations (E1 and E2) is insufficient to explain transient kinetic data.

Improved mammography with a reduced radiation dose.

A 2-cm-high focused air-interspaced grid with a 7:1 ratio and eight lamellae per inch was devised. The grid is arc-shaped and pivots on its focal point, the anode-cathode axis. Milliamperage was 35% less for breast phantom radiographs obtained with the new grid versus those obtained with a conventional 5:1 mammographic grid. In a comparison study of five mammograms, each evaluated for five parameters, the images obtained with the new grid were judged to be of equal or better quality than those obtained with a conventional grid in 17 of 20 comparisons.

The requirement of low calcium dialysate in patients on continuous ambulatory peritoneal dialysis receiving calcium carbonate as a phosphate binder.

In the present study we investigated the requirement of low calcium dialysate in 35 patients on continuous ambulatory peritoneal dialysis (CAPD) receiving calcium carbonate as the sole phosphate binder over a 12-month period. Patients with corrected serum calcium > or = 2.85 mmol/L after switching to oral calcium carbonate were given 1 to 3 2-litre exchanges of 2.5 mEq/L calcium dialysate. Serum phosphate level dropped from the pretreatment value of 2.95 +/- 0.62 to a level of between 1.70 +/- 0.41 to 2.03 +/- 0.44 mmol/L 2 weeks after therapy. Corrected serum calcium level increased significantly from 2 weeks onwards. Serum alkaline phosphatase rose initially at 2 and 6 weeks and decreased from 3 months onwards. Serum parathyroid hormone level dropped significantly from a mean pretreatment level of 569 to 320 pg/ml after 12 months (p < 0.001). Serum aluminum decreased significantly from a mean of 1.04 to 0.65 umol/L (p < 0.01). Daily calcium carbonate requirement fluctuated but tended to increase till 8 months and plateaued and ranged from 2.61 +/- 0.57 to 3.98 +/- 2.11 gm. The daily requirement of low calcium dialysate followed a similar trend with approximately three-quarters of patients ultimately requiring at least 1 bag of low calcium dialysate. Eight patients did not require low calcium dialysate. Patients who required low calcium dialysate were significantly older, had a significantly lower pretreatment serum parathyroid hormone and higher serum aluminum levels than those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)