Timing feedback-inhibition of the male reproductive hormone axis

Hormonal methods of male contraception have addressed feedback-inhbition of the cascade of hormones that has evolved to regulate sperm production but high concentrations of testosterone (T) in the blood have not worked satisfactorily. We hypothesized that an episodic event, such as degranulation of gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus, could be as well inhibited by episodic interference as by continuously-applied suppression. We used a computational model of hypothalamus-pituitary-gonad axis described by Veldhuis et al. to test the hypothesis that episodic administration of T would inhibit GnRH and/or luteinizing hormone (LH) secretion. A set of stochastic differential equations model feedback as well as feed-forward actions of GnRH, LH and T. The model predicted feedback-inhibition of GnRH pulses in a dose and frequency dependent manner when transdermal patches or injections delivering pulsatile T were applied. Since the published model did not address the effect of chronic GnRH deprivation on the viability of pituitary gonadotrophes, we introduced a function to address this issue. Incorporation of this function in the model allowed the prediction of a “holiday period” in the contraceptive regimen, during which exogenous T would not be needed to protect from conception. Pulsatile T delivered by real-life transdermal delivery system applied as per a parsimonious regimen reduced secretion of LH and T and fertility. The vitality function, proposed to account for survival and proliferation of pituitary gonadotrophes correlated with in vivo observations as extensive apoptosis in the anterior pituitary was observed after application of transdermal T

Photon transport in thin disordered slabs

We examine using Monte Carlo simulations, photon transport in optically 'thin' slabs whose thickness L is only a few times the transport mean free path l∗, with particles of different scattering anisotropies. The confined geometry causes an auto-selection of only photons with looping paths to remain within the slab. The results of the Monte Carlo simulations are borne out by our analytical treatment that incorporates directional persistence by the use of the Ornstein-Uhlenbeck process, which interpolates between the short time ballistic and long time diffusive regimes

Manuscrits lul·lians de la Biblioteca de Catalunya. I

We have studied the correlates of cell death during stalk cell differentiation in Dictyostelium discoideum. Our main findings are four. (i) There is a gradual increase in the number of cells with exposed phosphatidyl serine residues, an indicator of membrane asymmetry loss and increased permeability. Only presumptive stalk cells show this change in membrane asymmetry. Cells also show an increase in cell membrane permeability under conditions of calcium-induced stalk cell differentiation in cell monolayers. (ii) There is a gradual fall in mitochondrial membrane potential during development, again restricted to the presumptive stalk cells. (iii) The fraction of cells showing caspase-3 activity increases as development proceeds and then declines in the terminally differentiated fruiting body. (iv) There is no internucleosomal cleavage of DNA, or DNA fragmentation, in D. discoideum nor is there any calcium- and magnesium-dependent endonucleolytic activity in nuclear extracts from various developmental stages. However, nuclear condensation and peripheralization does occur in stalk cells. Thus, cell death in D. discoideum shows some, but not all, features of apoptotic cell death as recognized in other multicellular systems. These findings argue against the emergence of a single mechanism of 'programmed cell death (PCD)' before multicellularity arose during evolution

Imaging in turbid media using quasi-ballistic photons

We study by means of experiments and Monte Carlo simulations, the scattering of light in random media, to determine the distance upto which photons travel along almost undeviated paths within a scattering medium, and are therefore capable of casting a shadow of an opaque inclusion embedded within the medium. Such photons are isolated by polarisation discrimination wherein the plane of linear polarisation of the input light is continuously rotated and the polarisation preserving component of the emerging light is extracted by means of a Fourier transform. This technique is a software implementation of lock-in detection. We find that images may be recovered to a depth far in excess of what is predicted by the diffusion theory of photon propagation. To understand our experimental results, we perform Monte Carlo simulations to model the random walk behaviour of the multiply scattered photons. We present a new definition of a diffusing photon in terms of the memory of its initial direction of propagation, which we then quantify in terms of an angular correlation function. This redefinition yields the penetration depth of the polarisation preserving photons. Based on these results, we have formulated a model to understand shadow formation in a turbid medium, the predictions of which are in good agreement with our experimental results.Comment: LaTex 19 pages, 10 ps figures and 8 eps figures. psfig.sty included. (submitted to Optics Commumications

Small-worlds: How and why

We investigate small-world networks from the point of view of their origin. While the characteristics of small-world networks are now fairly well understood, there is as yet no work on what drives the emergence of such a network architecture. In situations such as neural or transportation networks, where a physical distance between the nodes of the network exists, we study whether the small-world topology arises as a consequence of a tradeoff between maximal connectivity and minimal wiring. Using simulated annealing, we study the properties of a randomly rewired network as the relative tradeoff between wiring and connectivity is varied. When the network seeks to minimize wiring, a regular graph results. At the other extreme, when connectivity is maximized, a near random network is obtained. In the intermediate regime, a small-world network is formed. However, unlike the model of Watts and Strogatz (Nature {\bf 393}, 440 (1998)), we find an alternate route to small-world behaviour through the formation of hubs, small clusters where one vertex is connected to a large number of neighbours.Comment: 20 pages, latex, 9 figure

Enhanced dissolution and bioavailability of gliclazide using solid dispersion techniques

Gliclazide is practically insoluble in water and its bioavailability is limited by dissolution rate. To enhance the dissolution rate and bioavailability the present study was aimed to formulate solid dispersions using different water soluble polymers such as polyethylene glycol 4000 (PEG 4000), polyethylene glycol 6000 (PEG 6000) using fusion method and polyvinyl pyrrolidone K- 30 (PVP K 30) by solvent evaporation method. The interaction of gliclazide with the hydrophilic polymers was studied by Differential Scanning Calorimetry (DSC), Fourier Transformation-Infrared Spectroscopy (FTIR) and X-Ray diffraction analysis. Solid dispersions were characterized for physicochemical properties like drug content, surface morphology and dissolution studies. Various factors like type of polymer and ratio of the drug to polymer on the solubility and dissolution rate of the drug were also evaluated. Pharmacokinetic studies of optimized formulation were compared with pure drug and marketed formulation in wistar rats. The dissolution of the pure drug and solid dispersion prepared with PVP K 30 (1:1) showed 38.3 + 4.5 % and 95 + 5.2 % release respectively within 30 min. Peak plasma concentration of pure drug, solid dispersion (PVP K 30) and marketed formulation was found to be 8.76 + 2.5, 16.04 + 5.5 and 9.24 + 3.6 μg/ml respectively, from these results it was observed that there is two fold increase in peak plasma concentration compared to pure drug. Solid dispersion is an effective technique in increasing solubility, dissolution rate and bioavailability of the poorly soluble drugs.Keywords: Gliclazide; solubility; solid dispersion; pharmacokinetics; peak plasma concentration; half lif

Understanding Behavioral Sources of Process Variation Following Enterprise System Deployment

This paper extends the current understanding of the time-sensitivity of intent and usage following large-scale IT implementation. Our study focuses on perceived system misfit with organizational processes in tandem with the availability of system circumvention opportunities. Case study comparisons and controlled experiments are used to support the theoretical unpacking of organizational and technical contingencies and their relationship to shifts in user intentions and variation in work-processing tactics over time. Findings suggest that managers and users may retain strong intentions to circumvent systems in the presence of perceived task-technology misfit. The perceived ease with which this circumvention is attainable factors significantly into the timeframe within which it is attempted, and subsequently impacts the onset of deviation from prescribed practice and anticipated dynamics

Malignant melanoma of the mandibular gingiva

Oral malignant melanoma is an infrequent neoplasia making up less than 1% of all melanomas, which exhibits much more aggressive behavior than those found on the skin. We present an aggressive case of oral malignant melanoma located on the mandibular gingiva in a 24-year-old male patient, who developed metastases to not only the regional lymph nodes but also the lungs and liver. The advanced stage of the disease contraindicated any surgical intervention and palliative chemotherapy was planned

Interventions to improve hand hygiene compliance in patient care

Four studies met the criteria for the review: two from the original review and two from the update. Two studies evaluated simple education initiatives, one using a randomized clinical trial design and the other a controlled before and after design. Both measured hand hygiene compliance by direct observation. The other two studies were both interrupted times series studies. One study presented three separate interventions within the same paper: simple substitutions of product and two multifaceted campaigns, one of which included involving practitioners in making decisions about choice of hand hygiene products and the components of the hand hygiene program. The other study also presented two separate multifaceted campaigns, one of which involved application of social marketing theory. In these two studies follow-up data collection continued beyond 12 months, and a proxy measure of hand hygiene compliance (product use) was recorded. Microbiological data were recorded in one study. Hand hygiene compliance increased for one of the studies where it was measured by direct observation, but the results from the other study were not conclusive. Product use increased in the two studies in which it was reported, with inconsistent results reported for one initiative. MRSA incidence decreased in the one study reporting microbiological data