Quantifying movement of multiple threatened species to inform adaptive management of environmental flows.

There is a growing need for water managers to refine and optimise environmental flow strategies (e-flows) to balance water requirements for humans and nature. With increasing demands for freshwater and consequent declines in biodiversity, managers are faced with the problem of how to adaptively manage e-flows for multiple stakeholders and species whose flow requirements may overlap or vary. This study assessed the effectiveness of a regulated e-flow release strategy from a dam, aimed at providing movement opportunities and facilitating reproductive processes for multiple threatened species. Movements of 24 Mary River cod (Maccullochella mariensis), 20 Australian lungfish (Neoceratodus forsteri) and 13 Mary River turtle (Elusor macrurus) were quantified using acoustic telemetry over a three-year period. The influence of regulated e-flow releases, season, river depth, water temperature and rainfall on animal movements was assessed using Generalised linear mixed models (GLMMs). Models showed that hydraulic connectivity provided by both natural flows and regulated e-flow releases facilitated movement of all three species between pool habitats, throughout the year. Mary River turtles made extensive use of regulated e-flow releases when moving between habitats, whereas Mary River cod and Australian lungfish required additional natural rises in river height above the regulated e-flows to trigger movements. Significant movement activity was also recorded for cod and turtles during the dry season (winter and spring), broadly coinciding with breeding periods for these species. The effectiveness of, and potential improvements to, current e-flow strategies to sustain key life-history requirements of these species is discussed. Findings suggest a revised e-flow strategy with relatively minor increases in the magnitude of e-flow releases throughout winter and spring, would be effective in providing movement opportunities and supporting reproductive success for all three species. This study demonstrates that by quantifying movement behaviour in an e-flow context, ecological risk assessment frameworks can then be used to assess and provide for critical life-history requirements of multiple species within the context of a highly regulated system under increasing water use demands.

A risk assessment approach to manage inundation of Elseya albagula nests in impounded waters: a win-win situation?

A risk assessment process was used to trial the impact of potential new operating rules on the frequency of nest inundation for the White-throated snapping turtle, Elseya albagula, in the impounded waters of the Burnett River, Queensland, Australia. The proposed operating rules would increase the barrage storage level during the turtle nesting season (May-July) and then would be allowed to reduce to a lower level for incubation for the rest of the year. These proposed operating rules reduce rates of nest inundation by altering water levels in the Ben Anderson Barrage impoundment of the Burnett River. The rules operate throughout the turtle reproductive period and concomitantly improve stability of littoral habitat and fishway operation. Additionally, the proposed rules are expected to have positive socio-economic benefits within the region. While regulated water resources will inherently have a number of negative environmental implications, these potential new operating rules have the capacity to benefit the environment while managing resources in a more sustainable manner. The operating rules have now been enacted in subordinate legislation and require the operator to maintain water levels to minimize turtle nest inundation.

Current opinion on large-scale prospective myomectomy databases toward evidence-based preconception and antenatal counselling utilising a standardised myomectomy operation note.

Background: No large-scale databases exist of pregnancy outcomes and rate of uterine rupture for women after myomectomy, resulting in inconsistent antenatal counselling and decision-making regarding mode and timing of delivery. Standardising information collected at myomectomy may facilitate data collection, informing prenatal/ antenatal counselling. Objectives: To determine clinician opinions regarding standardisation of myomectomy operation notes to allow comprehensive data input into a prospective database of pregnancy outcomes, toward an evidence-based approach to decision making regarding timing and mode of delivery in subsequent pregnancies. Materials and Methods: A google forms survey was emailed to all consultant (attending-level) obstetricians and gynaecologists across 25 hospitals in London, Kent, Surrey, and Sussex (UK) between March and May 2022. To enhance response rates, two further email reminders were sent alongside in-person reminders from selected local unit representatives. Main outcome measures: Senior clinician opinion for characteristics necessary to collect at time of surgery to develop a widescale database of post myomectomy pregnancy outcomes. Results: 209/475 (44%) responses received; 95% (198/209) agreed with standardising operation notes. Criteria selected for inclusion included cavity breach (98%, 194/198), location (98%, 194/198), number of fibroids removed (93%, 185/198) and number of uterine incisions (96%, 190/198). Conclusions: Gynaecologists support standardising myomectomy operation notes to inform the development of prospective large-scale databases of pregnancy outcomes after myomectomy. What is new?: Acquisition of clinician opinions on the development and content of a standardised myomectomy operation note to aid the development of a pregnancy-outcome database for women after myomectomy.

Towards a clinical consensus on the management of pregnancy and birth after laparoscopic and open myomectomy: A survey of obstetricians and gynaecologists.

OBJECTIVES: The primary aim was to assess if a clinical consensus regarding the management of pregnancy post myomectomy existed amongst consultant obstetricians and gynaecologists. Secondary objectives were to evaluate factors which influence the clinician's decision making in this group of women. STUDY DESIGN: Electronic survey sent to all consultants working in the North Central and East London deanery, Kent Surrey and Sussex deanery and Imperial NHS Trust to assess opinions on mode of birth post myomectomy, intervals advised to pregnancy post myomectomy, factors influencing the management of delivery in the scarred uterus post myomectomy, opinions on induction of labour and questions relating to operative notes. RESULTS: 209 consultant responses received between 07/03/2022-07/05/2022 (44% response rate); 77% (161/209) practicing obstetricians and gynaecologists, 10% (21/109) pure gynaecologists and 13% (27/209) pure obstetricians. The majority would support a vaginal birth after open myomectomy (75%) and laparoscopic myomectomy (79%). No consensus was found as to the optimal time interval between myomectomy and pregnancy. Higher frequency of performing myomectomy and a greater level of experience were significantly associated with a shorter interval to pregnancy advised. The most important operative factors influencing decision to support trial of labour post myomectomy were breach of uterine cavity; location of fibroids removed and number of incisions on the uterus. 77% believe women should be given a choice regarding mode of delivery post myomectomy in a similar way to previous LSCS. 82.8% would support enrolment of patients into a prospective trial to investigate delivery post myomectomy. CONCLUSIONS: We present a comprehensive survey of clinician opinions on pregnancy post myomectomy demonstrating that the majority of consultant obstetricians and gynaecologists sampled would support vaginal birth post myomectomy; counselling patients in a similar way to VBAC; a standardised myomectomy operation note and enrolment of patients in a future prospective trial. Wide variation in opinion regarding interval to pregnancy post myomectomy has been highlighted. We believe this information will facilitate counselling discussions and empower women with subsequent pregnancies after myomectomy to make an informed decision on mode of birth post myomectomy.

Low positive predictive value of the ABCD2 score in emergency department transient ischaemic attack diagnoses: the South Western Sydney transient ischaemic attack study.

BACKGROUND: The ABCD(2) stroke risk score is recommended in national guidelines for stratifying care in transient ischaemic attack (TIA) patients, based on its prediction of early stroke risk. We had become concerned about the score accuracy and its clinical value in modern TIA cohorts. METHODS: We identified emergency department-diagnosed TIA at two hospitals over 3 years (2004-2006). Cases were followed for stroke occurrence and ABCD(2) scores were determined from expert record review. Sensitivity, specificity and positive predictive values (PPV) of moderate-high ABCD(2) scores were determined. RESULTS: There were 827 indexed TIA diagnoses and record review was possible in 95.4%. Admitted patients had lower 30-day stroke risk (n = 0) than discharged patients (n = 7; 3.1%) (P < 0.0001). There was no significant difference in proportion of strokes between those with a low or moderate-high ABCD(2) score at 30 (1.2 vs 0.8%), 90 (2.0 vs 1.9%) and 365 days (2.4 vs 2.4%) respectively. At 30 days the sensitivity, specificity and PPV of a moderate-high score were 57% (95% confidence interval (CI) 25.0-84.2), 32.2% (95% CI 29.1-35.6) and 0.75% (95% CI 0.29-1.91) respectively. CONCLUSIONS: Early stroke risk was low after an emergency diagnosis of TIA and significantly lower in admitted patients. Moderate-high ABCD(2) scores did not predict early stroke risk. We suggest local validation of ABCD(2) before its clinical use and a review of its place in national guidelines.

Cytoplasmic domains in eggs.

One way of organizing the body plan of a developing embryo is to establish domains in the egg with distinct compositions in defined spatial relationships to one another: when the egg divides up, these domains segregate preferentially to certain regions of the embryo and influence their development. In this review we discuss the nature, formation and reorganization of distinguishable domains in various eggs.

Redundant mechanisms of calcium-induced calcium release underlying calcium waves during fertilization of sea urchin eggs.

Propagating Ca2+ waves are a characteristic feature of Ca(2+)-linked signal transduction pathways. Intracellular Ca2+ waves are formed by regenerative stimulation of Ca2+ release from intracellular stores by Ca2+ itself. Mechanisms that rely on either inositol trisphosphate or ryanodine receptor channels have been proposed to account for Ca2+ waves in various cell types. Both channel types contributed to the Ca2+ wave during fertilization of sea urchin eggs. Alternative mechanisms of Ca2+ release imply redundancy but may also allow for modulation and diversity in the generation of Ca2+ waves.

Adjuvant immunosuppression for paradoxical deterioration in tuberculous meningitis including one case responsive to cyclosporine. A tertiary referral hospital experience.

BACKGROUND: Tuberculous meningitis (TBM) accounts for 1-4% of all tuberculosis (TB) presentations. Paradoxical deterioration in non-HIV patients is a common manifestation of anti-tuberculosis therapy, characterised by clinico-radiological deterioration. We report a case series of TBM admissions to our institution including one case with paradoxical deterioration refractory to corticosteroids who responded to adjuvant cyclosporine. METHODS: Retrospective review of 12 HIV-negative patients admitted to Liverpool Hospital, Sydney (2005-2016) with laboratory and/or radiologically confirmed TBM. RESULTS: Median patient age was 40 (range 22-81 years), M:F = 7:5. Eleven patients (92%) were of Asia-Pacific origin. Eleven initially presented with central nervous system manifestations and one had preceding miliary TB. Nine patients had extra-cranial TB involvement including eight with past or current pulmonary disease. Cerebrospinal fluid (CSF) TB PCR/culture was positive in 10 patients. Paradoxical deterioration developed in three patients despite concomitant corticosteroids in two. One patient with paradoxical deterioration was refractory to corticosteroids: A 22-year-old Vietnamese male with TBM developed worsening headaches and altered mentation after seven weeks concomitant anti-TB and corticosteroid treatment. Interval MRI brain demonstrated increased size and number of tuberculomas as well as hydrocephalus. Cyclosporine was added with gradual improvement and ultimately good outcome. CONCLUSION: Our case series highlights the seriousness of paradoxical deterioration in TBM and the potential role of adjuvant cyclosporine in patients refractory to corticosteroids.

Function and characteristics of repetitive calcium waves associated with meiosis.

BACKGROUND: Internal calcium waves and oscillations are now recognized as universal features of cellular activation, but their exact role remains uncertain. In mammalian and ascidian eggs, a large, sperm-triggered calcium activation wave crosses the egg at fertilization, followed by a series of periodic increases in intracellular calcium concentration ([Ca2+]i). We have previously shown that, in eggs of the ascidian Phallusia mammillata, these periodic, post-activation [Ca2+]i increases are in the form of waves, the origin of which relocalizes to a pacemaker region, and that they stop seconds before the completion of meiosis. RESULTS: We show here that the origin of the first one to four post-activation calcium waves in P. mammillata eggs transfers progressively from the site of sperm entry, usually in the animal hemisphere, towards an endoplasmic reticulum (ER)-rich contraction pole in the vegetal hemisphere, a process that takes about five minutes. Once the origin of these repetitive post-activation calcium waves has reached the contraction pole, all subsequent calcium waves originate from the domain of ER concentrated there, which acts as a pacemaker. The first few post-activation calcium waves are faster than the activation wave and, like the activation wave, they propagate homogeneously throughout the cytoplasm. Approximately five to ten minutes after fertilization, the post-activation calcium waves begin to propagate preferentially in the egg cortex. By manipulating intracellular calcium levels with caged inositol 1,4,5 trisphosphate (InsP3) and a competitive inhibitor of InsP3-induced calcium release, we show that the activation wave induced by the sperm is sufficient to induce extrusion of the first polar body, but that additional [Ca2+]i increases are necessary for completion of the second meiotic division. However, periodic calcium waves per se do not seem to be strictly necessary for the completion of meiosis, as a persistent and homogeneous increase in calcium, induced by the calcium ionophore ionomycin, is sufficient to cause second polar body formation and allow completion of meiosis on time. CONCLUSION: These results clearly show that, in the ascidian egg, post-activation calcium waves are required to complete meiosis. They also show that following a period of progressive relocalization of the wave origin, which lasts approximately five minutes, an ER-rich domain at the contraction pole finally becomes a pacemaker from which the calcium waves originate. Once their origin becomes stably localized, the calcium waves begin to propagate preferentially around the cortex of the egg rather than throughout the egg cytoplasm.

Internal calcium release and activation of sea urchin eggs by cGMP are independent of the phosphoinositide signaling pathway.

We show that microinjecting cyclic GMP (cGMP) into unfertilized sea urchin eggs activates them by stimulating a rise in the intracellular free calcium ion concentration ([Ca2+]i). The increase in [Ca2+]i is similar in both magnitude and duration to the transient that activates the egg at fertilization. It is due to mobilization of calcium from intracellular stores but is not prevented by the inositol trisphosphate (InsP3) antagonist heparin. Furthermore, cGMP does not stimulate the eggs Na+/H+ antiport when the [Ca2+]i transient is blocked by the calcium chelator bis-(O-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA), suggesting that cGMP does not activate eggs by interacting with the their phosphoinositide signaling pathway. However, the [Ca2+]i increase and activation are prevented in eggs in which the InsP3-sensitive calcium stores have been emptied by the prior microinjection of the InsP3 analogue inositol 1,4,5-trisphosphorothioate. These data indicate that cGMP activates eggs by stimulating the release of calcium from an InsP3-sensitive calcium store via a novel, though unidentified, route independent of the InsP3 receptor.

Collaboration and entanglement: An actor-network theory analysis of team-based intraprofessional care for patients with advanced heart failure.

Despite calls for more interprofessional and intraprofessional team-based approaches in healthcare, we lack sufficient understanding of how this happens in the context of patient care teams. This multi-perspective, team-based interview study examined how medical teams negotiated collaborative tensions. From 2011 to 2013, 50 patients across five sites in three Canadian provinces were interviewed about their care experiences and were asked to identify members of their health care teams. Patient-identified team members were subsequently interviewed to form 50 "Team Sampling Units" (TSUs), consisting of 209 interviews with patients, caregivers and healthcare providers. Results are gathered from a focused analysis of 13 TSUs where intraprofessional collaborative tensions involved treating fluid overload, or edema, a common HF symptom. Drawing on actor-network theory (ANT), the analysis focused on intraprofessional collaboration between specialty care teams in cardiology and nephrology. The study found that despite a shared narrative of common purpose between cardiology teams and nephrology teams, fluid management tools and techniques formed sites of collaborative tension. In particular, care activities involved asynchronous clinical interpretations, geographically distributed specialist care, fragmented forms of communication, and uncertainty due to clinical complexity. Teams 'disentangled' fluid in order to focus on its physiological function and mobilisation. Teams also used distinct 'framings' of fluid management that created perceived collaborative tensions. This study advances collaborative entanglement as a conceptual framework for understanding, teaching, and potentially ameliorating some of the tensions that manifest during intraprofessional care for patients with complex, chronic disease.

Creb1 regulates late stage mammalian lung development via respiratory epithelial and mesenchymal-independent mechanisms.

During mammalian lung development, the morphological transition from respiratory tree branching morphogenesis to a predominantly saccular architecture, capable of air-breathing at birth, is dependent on physical forces as well as molecular signaling by a range of transcription factors including the cAMP response element binding protein 1 (Creb1). Creb1(-/-) mutant mice exhibit complete neonatal lethality consistent with a lack of lung maturation beyond the branching phase. To further define its role in the developing mouse lung, we deleted Creb1 separately in the respiratory epithelium and mesenchyme. Surprisingly, we found no evidence of a morphological lung defect nor compromised neonatal survival in either conditional Creb1 mutant. Interestingly however, loss of mesenchymal Creb1 on a genetic background lacking the related Crem protein showed normal lung development but poor neonatal survival. To investigate the underlying requirement for Creb1 for normal lung development, Creb1(-/-) mice were re-examined for defects in both respiratory muscles and glucocorticoid hormone signaling, which are also required for late stage lung maturation. However, these systems appeared normal in Creb1(-/-) mice. Together our results suggest that the requirement of Creb1 for normal mammalian lung morphogenesis is not dependent upon its expression in lung epithelium or mesenchyme, nor its role in musculoskeletal development.

Treatment of progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome with intravenous immunoglobulin in a patient with multiple sclerosis treated with fingolimod after discontinuation of natalizumab.

We report a case of progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome in a multiple sclerosis (MS) patient 3.5 months after fingolimod commencement and 4.5 months after natalizumab (NTZ) cessation. Three cerebrospinal fluid analyses were required before a definitive diagnosis of progressive multifocal leukoencephalopathy was reached. Intravenous immunoglobulin (IVIG) was subsequently given as the sole MS treatment along with mirtazapine and mefloquine. There has been improvement and subsequent clinical stabilization. The notable features are the difficult timing of fingolimod commencement in the context of previous NTZ therapy, the role of repeated cerebrospinal fluid John Cunningham virus analyses in progressive multifocal leukoencephalopathy diagnosis, and the role of IVIG.

Thermography of the nose and ear in relation to the skin lesions of lepromatous leprosy, tuberculosis, leishmaniasis, and lupus pernio.

The nasal and aural temperature patterns of 100 normal subjects have been investigated by infrared thermography, paying particular attention to possible errors of instrumentation and technique which may arise in such areas of complex morphology. Although by no means invariable, the pattern of themograms confirms that certain areas which are relatively cool are often affected in lepromatous leprosy, tuberculosis, leishmaniasis, and lupus pernio. In lepromatous leprosy, low temperature appears to govern the localization of disease in most parts of the body, and the possible reasons for this are discussed. Thermography may have a place in the investigation of other skin diseases in which the distribution of lesions on the body surface is unexplained.

Treatment of multiple sclerosis with the monoclonal anti-CD4 antibody cM-T412: results of a randomized, double-blind, placebo-controlled, MR-monitored phase II trial.

We report the results of a randomized, double-blind, placebo-controlled exploratory trial of the chimeric monoclonal anti-CD4 antibody cM-T412 in 71 patients suffering from active relapsing-remitting and secondary progressive multiple sclerosis. Infusion of the antibody produced frequent but usually minor side effects and resulted in a long-lasting reduction of circulating CD4-positive T cells. There was no significant effect on the primary measure of efficacy, the number of active lesions on monthly gadolinium-enhanced MRI over 9 months. Further statistical evaluation provided evidence that the degree of depletion of CD4-positive cells was important with regard to treatment efficacy; using CD4 counts as a covariate there was a statistically significant effect on the number of active lesions over 18 months (p = 0.04). There was a statistically significant reduction of 41% in the number of clinical relapses (a secondary efficacy parameter) after 9 months (p = 0.02), which was still present after 18 months, but this finding may be partly due to physician unblinding. Other secondary efficacy parameters (Expanded Disability Status Scale progression, number of courses of methylprednisolone) were not influenced by anti-CD4 treatment. We conclude that intravenous treatment with the monoclonal antibody cM-T412 in the dosage we used results in a substantial and sustained reduction of the number of circulating CD4-positive cells, but is not able to reduce MS activity as measured by monthly gadolinium-enhanced MRI, and is therefore unlikely to have a beneficial effect on the clinical disease course. We found preliminary evidence suggesting that more aggressive depletion of CD4-positive cells might lead to a more substantial reduction in MRI activity.

The effect of cloprostenol on human luteal steroid and prostaglandin secretion in vitro.

1 Human luteal tissue slices from days 18, 21 and 25 of the menstrual cycle were superfused in vitro with Medium 199 alone or containing cloprostenol (1 microgram/ml). Concentrations of progesterone, oestradiol-17beta and prostaglandins F2alpha and E2 were determined in the superfusate samples. 2 Secretion of steroids and prostaglandins was maintained at an approximately constant level throughout the experiments (21 h in one case) when the tissue was perfused with M199 alone. 3 Superfusion with cloprostenol (1 microgram/ml) resulted in an initial depression of progesterone and oestradiol-17beta but this was not maintained, levels returning to control values or showing an increase, while superfusion with cloprostenol continued. Cloprostenol is not therefore considered to be luteolytic at this dose and under these conditions for human luteal tissue in vitro. 4 Superfusion with cloprostenol (1 microgram/ml) also resulted in a large stimulation of secretion of endogenous prostaglandin F2 alpha following a short lag phase. This stimulation was possibly due to the initial depression of progesterone secretion. A short-lived stimulation of prostaglandin E2 secretion was also observed. 5 The significance of the increase in prostaglandin E2 secretion and the interrelationships between the various changes observed with cloprostenol are difficult to interpret.

The penetration of dapsone, rifampicin, isoniazid and pyrazinamide into peripheral nerves.

1 Dapsone, rifampicin, isoniazid and pyrazinamide were shown to penetrate readily into the sciatic nerves of the dog and sheep. 2 These findings suggest that the continued persistence of viable drug-sensitive leprosy bacilli in the peripheral nerves of patients treated for long periods with either dapsone or rifampicin is not due to inadequate intraneural drug penetration.

Road traffic injuries in Sharjah.

Hospital data of all patients seen as a result of road traffic accident injuries are presented for the year 1977. A follow-up study was carried out in December 1978 of those patients admitted with fractures of the skull and spine. The road traffic accident rate was 810 per 100 000 and the death rate was 25 per 100 000. All the deaths in hospitals were due to skull fractures. A third of those with cervical spine fractures were discharged with serious permanent disabilities. The problems of planning health services for this most unusual population are discussed.

Factor VIII related antigen positive macrophages and acquired immune deficiency syndrome (AIDS): a problem of antibody specificity.

A further histopathological complication of atypical mycobacterial infection in acquired immune deficiency syndrome (AIDS) is reported. Positive reactivity between mycobacterial antibodies within a polyclonal antiserum and mycobacteria within tissues resulted in false positivity with this reagent to factor VIII related antigen. This complication may be avoided either by prior testing of the antiserum, or by purification, or by the use of monoclonal antibodies. Histopathologists examining tissues from patients with AIDS and those with disseminated mycobacterial infections and using immunohistochemical techniques should be aware of this occurrence.

Airborne infection with Mycobacterium leprae in mice.

Although the portal of entry and mode of spread of M. leprae in human leprosy are still uncertain, it is widely held that direct person-to-person skin contact is important. This assumption has ignored the fact that patients with highly bacilliferous leprosy have nasal as well as dermal infection and that, since M. leprae is shed predominantly from the nose, leprosy might be an airborne infection. The present study was designed to investigate this possibility with mice exposed to airborne infection with M. leprae. The conditions are described in which thymectomised-irradiated CBA strain mice exposed to M. leprae aerosols sustained an immediate lung retention of 1 X 10(5) bacteria. Fourteen to 24 months later, 33% (10 of 30) of the mice had countable numbers of acid-fast bacilli (greater than 2 X 10(4)) with the characteristics of M. leprae in one or more homogenates prepared from ears, foot pads, nose or lungs. Evidence is presented from the distribution of M. leprae that the infection had arisen from systemic spresd of bacilli initially entering the lungs rather than from multiplication of organisms locally retained there, or in the nose, at the time of airborne infection. The relevance of these results to the possible route of infection of leprosy in man is discussed.