The PERCIVAL detector: first user experiments.

The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.

Rapid photoperiodic responses in Japanese quail: is daylength measurement based upon a circadian system?

Experimental photoperiods, presented either once only or repeatedly, were used to assess the oscillatory and hourglass properties of the photoperiodic clock in Japanese quail. Gonadectomized quail on 8-hr daylengths respond to a single skeleton photoperiod consisting of two 8-hr light pulses separated by 2 hr of darkness (i.e., LDLD 8:2:8:6) with a marked increase in secretion rate of luteinizing hormone (LH). This response suggests that the second light pulse interacts with a "photoinducible phase" (phi i) lying some 10-16 hr from "dawn" (start of the first light pulse). If, however, groups of quail maintained on 8-hr daylengths are transferred to continuous darkness (DD), and the position of the phi i is sought by a single 8-hr light pulse applied at various times on the first or third day of DD, then an increase in circulating LH is, at best, barely detectable. It would appear that a strongly responsive phi i does not recur rhythmically in DD. Instead, the light pulse apparently acts primarily as a "dawn" signal that triggers a single cycle of photoinducibility, since a second 8-hr light pulse, placed to begin 2 hr after the end of the first, induces a large increase in plasma LH. Similar results are obtained if any single 8-hr light pulse presented to animals held in darkness is preceded, 10 hr earlier, by a short "dawn" light signal. Such dawn signals can be effective when very short; a pulse of only 30 sec can cause a subsequent phi i. The dawn pulse is effective at any circadian phase and leads to a single cycle in photoinducibility. In contrast, a much longer light pulse (perhaps not less than 4 hr) is needed to interact with phi i if significant gonadotropin secretion is to be stimulated. In confirmation of the findings described above, we found that Nanda-Hammer lighting schedules have remarkably little effect in stimulating gonadotropin secretion in gonadectomized quail. There is, for example, a very marked difference between the effectiveness of "resonating" schedules such as LD 6:6, which stimulates a high LH secretion rate since each "inductive" light pulse is preceded by an appropriate "dawn" signal, and a theoretically effective schedule such as LD 6:30, which induces a very small response by comparison. Such schedules (even theoretically noninductive ones) can, however, be made very highly inductive if alternate light pulses are preceded by an appropriately positioned 15-min light pulse to act as "dawn."

Thyroxine induces photorefractoriness and stimulates prolactin secretion in European starlings (Sturnus vulgaris).

When subjected to 11 h daylengths starlings do not become photorefractory and remain reproductively mature indefinitely. Male birds kept in these conditions were treated for 5 weeks with thyroxine, administered in the drinking water at a concentration of 0.056 m mol/l. By the end of this period, their testes had fully regressed and they were then transferred to 18 h daylengths. No subsequent testicular development was noted and the birds were apparently photorefractory. Several other phenomena characteristic of the refractory state were also induced by the thyroxine treatment, namely change in bill colour from yellow to black, moulting of the flight feathers and a marked increase in plasma prolactin levels. These observations suggest that thyroid hormones may be responsible for termination of reproduction in this species.

Changes in plasma prolactin in male starlings during testicular regression under short days compared with those during photorefractoriness.

Male starlings which had fully developed testes under 11-h daily photoperiods were subjected for 10 weeks to daylengths either increasing or decreasing by 30 min per week. In both cases testicular regression occurred; in the former case this was complete due to photorefractoriness, and was accompanied by a postnuptial moult and a marked (P less than 0.01) rise in plasma prolactin concentration. In the latter case the rate of gonadal regression was slow and variable and no moulting was observed. Plasma prolactin remained very low. Eventually the birds which had experienced decreasing photoperiods were transferred to long (16 h) days; they were shown to be photosensitive since their testes redeveloped rapidly. There was also a rise in plasma prolactin, the birds eventually showed the full testicular regression characteristic of photorefractoriness, and moulting occurred. These results show that raised prolactin secretion is not associated with short-day-induced testicular regression but only with long-day-induced photorefractoriness.

Influences of thyroidectomy and thyroxine replacement on photoperiodically controlled reproduction in quail.

The breeding season in quail ends when they become relatively refractory to long photoperiods. The processes underlying the development of this refractoriness are dependent upon the thyroid gland. Thyroidectomized male Japanese quail transferred from short (8 h light: 16 h darkness; 8L: 16D) to long (20L:4D) daily photoperiods mature their gonads and develop the androgen-dependent cloacal gland at rates only marginally slower than controls. However, when the birds are retransferred to short days thyroidectomized individuals do not show the rapid testicular regression and moult which occurs in controls under such conditions. The testes remain large for a long period, eventually decreasing in size slowly and irregularly. Once such thyroidectomized birds are transferred back to short days the administration of thyroxine has little effect upon the slow rate of gonadal regression but if the hormone is administered during the preceding period of long days normal regression does occur under short days, even though treatment has ceased. This suggests that a process dependent upon thyroid hormones takes place under long day-lengths that ensures the termination of reproduction when they are exposed either to short daylengths or to decreasing daylengths after the summer solstice. This view was substantiated by further experiments in which thyroidectomy was performed after the birds had been exposed to long daylengths. When transferred to 8L:16D normal testicular regression and moult occurred rapidly. Presumably the thyroid-dependent process had proceeded to an adequate extent in these quail before the thyroid glands were destroyed. Further support came from treating intact quail chronically with thyroxine. Its administration to quail on 20L:4D had no observable effect; the testes grew rapidly to maximal size and remained large. However, if the birds were given thyroxine under 12L:12D the gonads first developed to maximal size and then, after about 12 weeks of treatment, regressed spontaneously whether or not thyroxine was still being administered. It seems that thyroxine had made the quail so relatively refractory that 12L:12D was no longer sufficiently stimulatory to overcome the developing inhibition on the photoperiodic system. The results in quail are very reminiscent of the finding that the absolute photorefractoriness and spontaneous testicular regression which develops in starlings under long daylengths is thyroid dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Thyroidectomy of nestling starlings appears to cause neotenous sexual maturation.

Nestling starlings (Sturnus vulgaris) were thyroidectomized, in the wild, when 8 days old. They were later brought into captivity and hand reared on a daylength of 16h light: 8h darkness per day. Thyroidectomy dramatically affected somatic development so that even at 23 weeks of age these birds retained the physical characteristics of approximately 3-week-old euthyroid birds. Nevertheless, they appeared to be healthy and were active. Despite retaining juvenile features, these thyroidectomized birds became sexually mature. In males, testicular growth began at 8 weeks of age and by 23 weeks both males and females had well developed gonads.

Thyroxine treatment facilitates prolactin secretion and induces a state of photorefractoriness in thyroidectomized starlings.

Sexually immature male starlings were radiothyroidectomized while held under short day-lengths. They were then subjected to long (18-h) photoperiods and the testes developed rapidly and apparently normally to full maturity. As expected, thyroidectomy prevented an onset of photorefractoriness and after 140 days the testes were still fully developed (testicular width 6.5 +/- 0.8 mm). Half of the birds were then given thyroxine (0.011 mmol/l) in the drinking water for 14 days while the others were maintained as controls. At the end of this time the birds still had fully developed gonads (testicular width 7.8 +/- 0.3 mm) but after a further 14 days testicular regression began in the thyroxine-treated birds. The testes of all individuals in this group were fully regressed (width 1.8 +/- 0.1 mm) by 56 days after the end of thyroxine administration and moulting of the flight feathers had begun. No recrudescence of the gonads was subsequently noted in the next 2 months and the birds were apparently photorefractory. The short period of thyroxine treatment also caused a rapid and prolonged increase in plasma prolactin levels from 2.0 +/- 0.3 to 16.8 +/- 2.6 micrograms/l. No testicular regression or moulting was observed in the control birds and their plasma prolactin levels remained very low (below 4.0 micrograms/l) throughout the experiment. In thyroidectomized and castrated starlings held on 18-h daylengths, 14 daily injections of thyroxine (100 micrograms/bird per day) caused a rapid and permanent decrease in circulating FSH to basal levels (reached about 36 days after thyroxine treatment began, at which time the birds moulted). The treatment also caused a marked increase in plasma prolactin lasting for about 50 days.

Endocrine changes associated with the termination of photorefractoriness by short daylengths and thyroidectomy in starlings (Sturnus vulgaris).

When starlings (Sturnus vulgaris) are transferred from short to long days, hypothalamic content of gonadotrophin-releasing hormone (GnRH) and pituitary gonadotrophin content eventually decrease, as birds become photorefractory, to values lower than they were on short days. This implies that both should increase as photorefractoriness is terminated some time after transfer from long to short days. Further, since thyroidectomy causes termination of photorefractoriness in birds held on long days, this should also result in an increase in hypothalamic GnRH and pituitary gonadotrophin contents. This study tests these hypotheses. Male starlings were transferred from short to long days for 10 weeks, by which time they should have become photorefractory. One group of birds was then killed; blood was collected, hypothalami and pituitaries were excised, and the stage of moult and testicular weights recorded. The remaining birds were then kept on long days, transferred to short days or thyroidectomized and kept on long days. Groups of birds in each treatment group were killed and sampled 2, 8 and 14 weeks later. Hypothalamic content of GnRH, and pituitary and plasma FSH and prolactin concentrations, were measured by radioimmunoassay. In birds sampled after 10 weeks of long days, hypothalamic content of GnRH was quite low, pituitary and plasma levels of FSH were very low, testes were small and pituitary and plasma prolactin levels were high. In intact birds kept on long days, hypothalamic GnRH content decreased further and remained low. Pituitary and plasma FSH levels remained low, testes remained small and pituitary and plasma prolactin levels decreased slowly.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothalamic gonadotrophin-releasing hormone and pituitary and plasma FSH and prolactin during photostimulation and photorefractoriness in intact and thyroidectomized starlings (Sturnus vulgaris).

Changes in concentrations of hypothalamic gonadotrophin-releasing hormone (GnRH) and pituitary and plasma FSH and prolactin were measured in intact and thyroidectomized female starlings (Sturnus vulgaris) after transfer from short to long photoperiods. In intact birds, hypothalamic GnRH did not increase significantly during the first 6 weeks of photo-stimulation, but by 12 weeks, as birds became photorefractory, it had decreased to levels significantly lower than those before photostimulation. In thyroidectomized birds, which did not become photorefractory, hypothalamic GnRH remained high after 12 weeks of photostimulation. Pituitary FSH increased in both intact and thyroidectomized birds; it then decreased to low levels in intact photorefractory birds, but remained high in thyroidectomized birds. Plasma FSH increased to a peak after 2 weeks, but by 6 weeks it had decreased to low levels in both groups. In intact birds there was a 70-fold increase in pituitary prolactin during the first 6 weeks, and levels were still high after 12 weeks of photostimulation. In thyroidectomized birds, pituitary prolactin remained low. The results suggest that while the initial effect of long daylengths is to cause gonadal maturation, the ultimate effect is to switch off the reproductive system.

A photoperiodic response in gonadectomized Japanese quail exposed to a single long day.

Gonadectomized male Japanese quail maintained on short daylengths (8 h light:16 h darkness) showed a reliable and repeatable response, in terms of increased gonadotrophin secretion, to a single long photoperiod (20 h light) followed by continuous darkness. Plasma levels of LH were significantly increased within 4 h of the end of the long day. Secretion continued to increase with time and LH and FSH concentrations reached a maximum some 24 h later, thereafter decreasing only slowly over the next 8-10 days. Quail could be used repeatedly at fortnightly intervals and gave a consistent response for at least 15 months. The size of the photoperiodic response and its considerable duration were much greater than found in intact quail. The birds showed a similar (though reduced) response if a short daylength was followed by a single 4-h light pulse interrupting the 16-h dark period. Using this system the time of maximum responsivity to the inductive effects of light lies 10-16 h from 'dawn'. The marked and rapid effects described provide an excellent experimental system in which to study how photoperiodic changes are recognized and how consequent neural activation is translated into enhanced secretion rates of hormones in the peripheral endocrine system.

Photoperiodic control of the development of the LHRH neurosecretory system of European starlings (Sturnus vulgaris) during puberty and the onset of photorefractoriness.

The development of the reproductive system was studied in juvenile starlings during the acquisition of photosensitivity, the attainment of sexual maturation after photostimulation and the subsequent onset of photorefractoriness, using immunohistochemistry for LHRH and radioimmunoassay measurements of hypothalamic, pituitary and plasma hormone concentrations. The first stage of sexual development induced by exposure of photorefractory immature starlings to short days (8 h light:16 h darkness; 8L:16D) was characterized by a decrease in pituitary prolactin content within 1 week and an increase in hypothalamic LHRH content, in the size of the LHRH perikarya and in the intensity of immunostaining in the median eminence in 4-6 weeks. Sexual maturation occurring after exposure to long days (18L:6D) was associated with further increases in LHRH content and cell size, and increases in LH and prolactin concentrations. During testicular regression, LHRH perikarya were reduced in size and staining intensity but LHRH immunostaining in the median eminence and content in the hypothalamus remained high until gonadal regression was almost complete. Prolactin levels were maximal during testicular regression. These results suggest that gonadal regression is initiated by a reduction in LHRH synthesis and possibly, in addition, an external inhibitory influence on LHRH release. Hypothalamic LHRH content eventually declined and LHRH immunostaining in the median eminence was much reduced in fully photorefractory starlings maintained under long days.

The effects of phenformin on the transport and metabolism of sugars by the rat small intestine.

The effects of 0.25-10 mM phenformin on sugar transport and metabolism have been studied in a preparation for the combined perfusion of the vascular bed and the lumen. At all concentrations the effects of vascular phenformin were more pronounced than those of luminal phenformin. Phenformin inhibited galactose transport across the intestine, the pattern of inhibition depending on whether the phenformin was added to the luminal or vascular compartments. The active accumulation of galactose in the mucosal epithelial cells was also abolished. There was a linear relationship between the percentage reduction in mucosal ATP levels and vascular phenformin concentration. Phenformin reduced the rate of glucose uptake from the lumen, and the proportion of this glucose which reached the vascular effluent. Most of the glucose which did not reach the vascular side could be accounted for by the formation of lactic acid. Vascular phenformin increased glucose uptake from the vascular medium by ca 88%, 97% of which could be accounted for by lactate formation. Phenformin was sequestered by the mucosa when added to the vascular, but not the luminal, perfusates. There was very little translocation of intact phenformin across the gut in either the mucosal or serosal directions. It is suggested that the effects of phenformin on the gut mainly derive from an inhibition of mitochondrial oxidative phosphorylation, with a small contribution from a direct effect on the brush border, more pronounced at high phenformin concentrations. The results are consistent with the idea that phenformin delays sugar absorption in man, and that the intestine may be a significant source of lactate production in lactic acidosis.

Prucalopride, a systemic enterokinetic, for the treatment of constipation.

BACKGROUND: Laxatives are frequently ineffective in treating constipation. An alternative therapeutic approach is to target serotonin-4 receptors, which are involved in initiating peristalsis. AIM: In a double-blind, placebo-controlled trial, to assess the efficacy and safety of a systemically active serotonin-4 agonist, prucalopride. METHODS: Seventy-four women with constipation were stratified into slow or normal transit groups, and each group was randomized to receive either placebo or 1 mg prucalopride daily for 4 weeks. A bowel function diary was maintained. Whole-gut and orocaecal transit, visceral sensitivity, quality of life and psychological state were assessed before and after treatment. RESULTS: Prucalopride, not placebo, increased spontaneous stool frequency (P=0.008) and reduced time to first stool (P < 0.001). Prucalopride reduced the number of retained markers in all patients compared to placebo (P=0.004). Prucalopride reduced the mean number of retained markers in slow transit (P=0.069), but did not alter the marker count in normal transit (P=0.86). Orocaecal transit was accelerated by prucalopride, not placebo (P=0.004). Prucalopride, notplacebo, increased rectal sensitivity to distension (urge volume, P=0.01) and electrical stimulation (P=0.001). Prucalopride significantly improved several domains of the Short Form Health Status Survey and the disease-specific quality of life. Adverse effects were similar for prucalopride and placebo. CONCLUSIONS: Prucalopride improves symptoms, upper gut transit and gut sensitivity in constipated patients with both slow and normal transit. It improves transit in patients with slow transit. These changes are associated with improved well-being.

Antibiotic prophylaxis in cardiac operations.

This clinical trial, which was composed of 1,031 adults undergoing cardiac operations, compared the efficacy of a single dose of 1 g of ceftriaxone with a 48-our regimen consisting of flucloxacillin and gentamicin. There was no significant difference (p = 0.89) in the overall incidence of major infections: 30 of 515 patients (5.8%; 95% confidence interval, 5.4% to 6.2%) taking ceftriaxone and 29 of 516 patients (5.6%; 95% confidence interval, 5.2% to 6.0%) taking flucloxacillin and gentamicin. Subgroup analyses, with a lower statistical power, failed to show a significant difference between patients who received ceftriaxone and those who received flucloxacillin/gentamicin: major sternal wound infections arose in 2.7% of the patients taking ceftriaxone versus 1.6% in those on the 48-hour regimen (p = 0.20) and major limb wound infections arose in 4.2% and 5.4%, respectively (p = 0.44). Single-dose prophylaxis was associated with fewer intravenous administrations (864 doses versus 9,570 doses) and cost less (A$17,248 versus A$78,510). Although the regimen that included gentamicin was associated with the greatest biochemical impairment of renal function, the overall toxicity for both groups was low. We conclude that a single dose of ceftriaxone provided cost-efficient prophylaxis for adults undergoing cardiac operations when compared with a 48-hour regimen of gentamicin and flucloxacillin. The general principle revealed by our data is that the short-term administration of an appropriate antibiotic regimen represents optimal prophylaxis for patients undergoing cardiac procedures.

Assessing risk for violence among psychiatric patients: the HCR-20 violence risk assessment scheme and the Psychopathy Checklist: Screening Version.

This study evaluated the predictive validity of the HCR-20 (Historical, Clinical, and Risk Management) violence risk assessment scheme and the Psychopathy Checklist: Screening Version (PCL:SV). Files of 193 civilly committed patients were coded. Patients were followed up in the community for an average of 626 days. Receiver operating characteristic analyses with the HCR-20 yielded strong associations with violence (areas under curve [AUCs] = .76-.80). Persons scoring above the HCR-20 median were 6 to 13 times more likely to be violent than those scoring below the median. PCL:SV AUCs were more variable (.68-.79). Regression analyses revealed that the HCR-20 added incremental validity to the PCL:SV and that only HCR-20 subscales predicted violence. Implications for risk assessment research, and the clinical assessment and management of violence, are discussed.

Organic acids in amniotic fluid.

The organic acids of human amniotic fluid were studied by gas chromatography and mass spectrometry. About 30 acids were identified. A "normal" metabolic profile of acids was established which can provide the basis for the identification of abnormal patterns.

Lyme disease spirochetes in ticks collected from birds in midwestern United States.

In a tick-spirochete survey conducted from all 1989 through fall 1992 in north-western Wisconsin, 4,256 birds (composed of 91 species) were examined for ticks. Infestations were recorded for 400 birds (composed of 30 species). Of 1,184 ticks taken from 335 birds (composed of 26 species), 60 (5%) Haemaphysalis leporispalustris (Packard) from 8 species of birds were infected with the Lyme disease spirochete. Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner. Similar surveys conducted in 1990 and 1991 in Minnesota and Michigan yielded 223 H. leporispalustris from 61 birds (composed of 23 species), all free of spirochetes. However, 1 B. burgdorferi-infected Ixodes scapularis (Say) was found on 1 bird species in Minnesota. Most ticks were collected in fall from ground-foraging birds such as thrushes and sparrows. These results confirm that tick-infested birds are important in disseminating Lyme disease spirochetes and may also play a role as sources for infecting ticks.

Lectins in drug delivery: a study of the acute local irritancy of the lectins from Solanum tuberosum and Helix pomatia.

Lectins are proteins or glycoproteins of non-immune origin capable of binding to one or more specific sugar residues. The potential for using lectins as a means of 'anchoring' a drug delivery system to the mucosal surfaces of the eye has been investigated in previous work, with the lectins from Solanum tuberosum and Helix pomatia showing particular promise. In this study the acute local dermal irritancy of these lectins, in terms of their potential to cause inflammation and tissue necrosis, was investigated. After an initial study in terminally anaesthetised animals (to ensure no gross toxicity was evident), five male New Zealand white rabbits from the same litter were briefly anaesthetised and Evans blue injected intravenously as a marker of inflammation. Sterile lectin solutions in normal saline at a range of concentrations from 50 to 500 microg ml(-1) were prepared and 50-microl volumes injected intradermally at 18 sites across a shaved area of each rabbit's back. The rabbits were then allowed to regain consciousness. There was no evidence of tissue necrosis, oedema or Evans blue infiltration with any of the lectin solutions administered. The rabbits did not display any signs of discomfort such as scratching or continued grooming throughout the experiment. Histological examination of the injection sites revealed little sign of any inflammation, such as heterophil migration, oedema or tissue damage. It was concluded that these lectins demonstrate minimal acute irritancy, and will, therefore, be taken forward for formulation and in vivo studies.

Detection of antibodies to Eperythrozoon ovis by the use of an enzyme-linked immunosorbent assay.

Specific antibody to Eperythrozoon ovis was detected by an enzyme-linked immunosorbent assay (ELISA) in the sera of infected sheep. In the presence of parasite antigen, positive control serum showed a reaction approximately eight times that of negative serum. When compared to an immunofluorescent antibody test (IFAT), the ELISA was eight times more sensitive. Positive control sera gave a titre of 1:3200 by IFAT and 1:25,600 by ELISA. Through the use of a reference titration curve ELISA could be used as a semi-quantitative system to determine antibody levels in test sera.

Public health hazards of meat from small ruminants: the perspective of Australia.

The production of meat from sheep and goats in Australia occurs almost entirely at pasture in zones known as the semi-arid pastoral zone, the wheat-sheep zone (where sheep and crops form an agricultural rotation system) and the high rainfall zone. Each zone has particular factors which affect the human health hazards associated with sheep and goat meat and the opportunities for prevention. The authors provide an overview of small ruminant production in Australia and a synopsis of the diseases encountered, including the factors which influence epidemiology. Animal health arrangements for underwriting food safety at the pre-harvest and post-harvest stages of production in Australia are also outlined. Specific public health hazards related to sheep and goat meat, together with measures for prevention, are considered under the headings of zoonoses, enteropathogens and chemical residues.