Major obstetric haemorrhage of 2000 ml or greater: a clinical audit.

Haemorrhage remains a leading cause of maternal death. We conducted an audit to identify strategies to improve the management at our local NHS Trust. A data collection form was based on our local guideline. A coded database search was conducted for all deliveries where the estimated blood loss was ≥2000 ml (from June 1 2015 to December 31 2015), returning 68 search results (13.7/1000 births). Fifty-six records were included. Poor compliance (<75%) was seen in some key areas including the major obstetric haemorrhage (MOH) call activation (52%), the presence of an anaesthetic consultant (63%) and tranexamic acid administration (46%). Thirty out of 56 cases (54%) were acutely transfused. Women, who were not transfused acutely, appeared to be more likely to need a secondary transfusion if no MOH call had been activated (9/27 (33%) versus 3/29 (10%), p = .052). A key area for improvement was the activation of MOH calls. Following this audit, we adjusted our guideline to make it more clinically useful and staff training sessions were held, including simulation training. Impact statement What is already known on this subject? A postpartum haemorrhage (PPH) is an obstetric emergency. A structured approach is important to optimise the care of the mothers during this dangerous time, and has been shown to reduce the transfusion requirements. However, clinical practice may not adhere to the guideline recommendations. What the results of this study add? With the objective evidence of increased rates of PPH ≥2000 ml at our institution, our work identifying the flaws in management was a critical component of the work to improve the outcomes. This study gives impetus to find innovative ways to improve adherence to guidelines, and inspired an update of our local guideline to improve the applicability and utility. This project suggests a new marker for the adequacy of an acute management (a requirement for secondary blood transfusion without having received an acute transfusion), and raises questions about what constitutes optimum PPH management. What the implications are of these findings for clinical practice and/or further research? The primary and secondary transfusion data raised new questions to investigate in the future: does the involvement of consultants and the escalation of care via the instigation of major haemorrhage protocols improve decision-making and patient outcomes? Does the necessity for a secondary transfusion indicate a suboptimal acute care?

Atmospheric peroxyacetyl nitrate (PAN): a global budget and source attribution.

Peroxyacetyl nitrate (PAN) formed in the atmospheric oxidation of non-methane volatile organic compounds (NMVOCs) is the principal tropospheric reservoir for nitrogen oxide radicals (NOx = NO + NO2). PAN enables the transport and release of NOx to the remote troposphere with major implications for the global distributions of ozone and OH, the main tropospheric oxidants. Simulation of PAN is a challenge for global models because of the dependence of PAN on vertical transport as well as complex and uncertain NMVOC sources and chemistry. Here we use an improved representation of NMVOCs in a global 3-D chemical transport model (GEOS-Chem) and show that it can simulate PAN observations from aircraft campaigns worldwide. The immediate carbonyl precursors for PAN formation include acetaldehyde (44% of the global source), methylglyoxal (30 %), acetone (7 %), and a suite of other isoprene and terpene oxidation products (19 %). A diversity of NMVOC emissions is responsible for PAN formation globally including isoprene (37 %) and alkanes (14 %). Anthropogenic sources are dominant in the extratropical Northern Hemisphere outside the growing season. Open fires appear to play little role except at high northern latitudes in spring, although results are very sensitive to plume chemistry and plume rise. Lightning NOx is the dominant contributor to the observed PAN maximum in the free troposphere over the South Atlantic.

Changes in plasma gonadotrophins, 17ß-oestradiol, progesterone, prolactin, thyroxine and triiodothyronine concentrations in female Japanese quail (Coturnix coturnix japonica) of a heavy body weight line during photo-induced ovarian growth and regression.

1. Simultaneous changes of the width of the cloacal opening and plasma luteinising hormone (LH), follicle stimulating hormone (FSH), 17ß-oestradiol, progesterone, prolactin, thyroxine (T(4)) and triiodothyronine (T(3)) during photo-induced ovarian growth and regression were measured in commercially bred Japanese quail from a heavy body weight line. 2. Somatically mature female Japanese quail were transferred from short days (light:dark 8L:16D) at 10°C to long days (16L:8D) at 20°C, and sexually mature female Japanese quail were transferred from long to short days. All variables were measured at transfer and every five days thereafter (except for a measurement at 12 instead of 10 d) for 35 d. 3. Transfer from short to long days caused significant increases in LH, FSH, 17ß-oestradiol, ovary weights and oviduct weights after five days, and in the cloacal opening after 12 d. T(3) decreased after five days, whereas no significant changes were observed in T(4) concentrations. Progesterone and prolactin both decreased after 25 long days. 4. The transfer of quail from long to short days caused significant decreases in LH, FSH, 17ß-oestradiol, progesterone, prolactin, ovary and oviduct weights after 12 d and an increase in T(3). There was no significant change in T(4) concentrations. The cloacal opening decreased after 25 short days. 5. These results are the first to show simultaneous changes in gonadotrophins, sex steroids, thyroid hormones and prolactin during photo-induced gonadal growth and regression in female Japanese quail.

The fallacy of the two-minute acid phosphatase cut off.

Research was carried out to determine whether the likelihood of obtaining a positive Acid Phosphatase (AP) test result is affected by the make and type of paper used. Also, we aimed to investigate the frequency of AP positive reactions occurring after 2min using a series of known semen dilutions and to determine whether spermatozoa transfer onto the paper during the act of AP screening. In this research, most brands of paper tested were able to detect a 1 in 40 semen dilution within 2min. Leaving AP test papers for longer will allow the detection of greater dilutions of semen and as the amount of ejaculation is not reliably known in most casework situations and levels of AP activity can vary in different men, this will increase the seminal detection rate in sexual offence allegations.

Long-term retention of injected aluminium-26.

Data previously reported on the whole-body retention of aluminium-26 ((26)Al) in a male volunteer are extended to 8 years after intravenous administration as citrate, when only ~2% of the injected tracer remained. The extended data, combined with a report elsewhere of the late urinary and faecal excretion of (26)Al by this subject, reinforce indications that transdermal losses contribute to the clearance of systemic aluminium and mitigate its long-term accumulation from chronic exposure.

Complex traits analysis of chicken growth using targeted genetical genomics.

Dissecting the genetic control of complex trait variation remains very challenging, despite many advances in technology. The aim of this study was to use a major growth quantitative trait locus (QTL) in chickens mapped to chromosome 4 as a model for a targeted approach to dissect the QTL. We applied a variant of the genetical genomics approach to investigate genome-wide gene expression differences between two contrasting genotypes of a marked QTL. This targeted approach allows the direct quantification of the link between the genotypes and the genetic responses, thus narrowing the QTL-phenotype gap using fewer samples (i.e. microarrays) compared with the genome-wide genetical genomics studies. Four differentially expressed genes were localized under the region of the QTL. One of these genes is a potential positional candidate gene (AADAT) that affects lysine and tryptophan metabolism and has alternative splicing variants between the two genotypes. In addition, the lysine and glycolysis metabolism pathways were significantly enriched for differentially expressed genes across the genome. The targeted approach provided a complementary route to fine mapping of QTL by characterizing the local and the global downstream effects of the QTL and thus generating further hypotheses about the action of that QTL.

Transfer of take-home messages in graduate ICU education.

PURPOSE: Teaching by lecture (lecture format) is widely used at congresses and in medical educational programmes. The process involves the transfer of take-home messages. The aim of this study was to assess the number of take-home messages identified by postgraduate critical care junior doctors (juniors) during lectures. METHODS: This was a prospective observational study of 13 lectures. Lecturers were not informed in advance of the study. At the end of the lecture (30 or 50 min), the lecturer (senior doctor) and juniors listed the three main take-home messages on a form. Subjective elements of the juniors' appraisal (quality of the presentation, explanation of the topic's relevance, enthusiasm of the lecturer, background, case-based, delivery and personality, comprehensibility, practical applicability of information given, prioritization, presence of raw data, references, overall satisfaction) and objective elements (length of lecture, number of take-home messages written on the slides) of the lectures were recorded. Successful knowledge transfer was assessed by matching lecturers' and juniors' take-home messages. RESULTS: In total, 367 forms completed by 367 juniors were analysed. A match equal to 3 (highest match), 2, 1 or 0 was observed in 3.8, 26.7, 48.2 and 21.2% of the forms, respectively. No single subjective or objective element of the lecture was associated with the number of identified take-home messages. CONCLUSIONS: Two-thirds of critical care junior doctors identified at best only one of the three main take-home messages of a lecture, suggesting that knowledge transfer is poor during passive format learning. These results suggest that there is a need to develop strategies to improve the performance of lecture-based learning.

Changes in plasma gonadotrophins, testosterone, prolactin, thyroxine and triiodothyronine concentrations in male Japanese quail (Coturnix coturnix japonica) of a heavy body weight line during photo-induced testicular growth and regression.

1. Simultaneous changes of cloacal gland area (CGA) and plasma luteinising hormone (LH), follicle stimulating hormone (FSH), testosterone (T), prolactin (PRL), thyroxine (T(4)) and triiodothyronine (T(3)) during photo-induced testicular growth and regression were measured in commercially bred Japanese quail from a heavy body weight line. 2. Somatically mature male Japanese quail were transferred from short days (light:dark 8L:16D) at 10°C, to long days (16L:8D) at 20°C; and sexually mature male Japanese quail were transferred from long to short days. All variables were measured at transfer and every 5 d thereafter for 35 d. 3. Transfer from short to long days caused significant increases in LH, FSH, T and testis weight (TW) after 5 d, and in CGA after 10 d. T(3) decreased after 5 d, whereas T(4) increased significantly after 25 long days and PRL did not undergo any consistent change. The testicular growth rate was k = 0·1146. 4. Transferring quail from long to short days caused significant decreases in LH and FSH after 5 d, and decreases in T, TW and CGA after 10 d. T(4) decreased after 5 d whilst T(3) increased significantly by day 15. PRL decreased significantly after 10 d then rose before declining again. The testicular regression rate was k = 0·0582. 5. The rates of photo-induced testicular development and regression in a strain of large Japanese quail did not differ from rates reported for other strains of quail. CGA was a better indicator of TW than plasma T concentrations during growth and regression. The role of PRL in photo-induced reproductive cycles in male Japanese quail remains to be determined. 6. The photoperiod-induced changes in gonad size and hormone concentrations, together provide valuable information that can be used in future studies of the endocrinology and neuroendocrinology of photoperiodism in birds.

New hypotheses on the function of the avian shell gland derived from microarray analysis comparing tissue from juvenile and sexually mature hens.

Activation of the shell gland region of the avian oviduct is mediated by ovarian steroids. To understand more extensively how shell glands are maintained and function, we have compared gene expression in the shell glands from juvenile and laying hens using a chicken cDNA microarray. Average expression profiles of juvenile and sexually mature shell glands were compared resulting in the identification of 266 differentially regulated genes. Reverse transcription quantitative polymerase chain reaction confirmed expression differences. The differentially expressed genes included several with known involvement in shell gland function, including ion transport and shell matrix proteins. There were also many unpredicted differentially expressed genes, and for some we propose hypotheses for their functions. These include those encoding (a) osteoprotegerin, a decoy death receptor for receptor activator of nuclear factor NFkB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), that in the shell gland, may prevent apoptosis and/or may have an endocrine effect by preventing RANKL's action on bone osteoclasts that mobilize stored calcium; (b) prostatic acid phosphatase (ACPP) and prostate stem cell antigen (PSCA) that could play a role in sperm physiology within the shell gland; (c) urea transporter (SLC14A2) that could provide a novel anti-microbial defence; (d) bactericidal/permeability-increasing protein-like 2 (BPIL2), and other potential anti-microbials that have not previously been documented in the chicken. These new hypotheses, if borne out experimentally, will lead to a greater understanding of shell gland function including the processes involved in eggshell formation and anti-microbial activity.

Timely closure of loop ileostomy following anterior resection for rectal cancer.

The implications of constructing a temporary ileostomy as part of the primary surgery for some rectal cancers must not be underestimated and many patients are particularly keen to have their stoma closed as early as possible. Currently, there are no set protocols in place which determine when this should take place, meaning that stoma reversal can be extremely variable between hospitals in the UK. We have created a policy to give patients a provisional date for ileostomy closure at discharge from primary surgery, which takes into account any necessary adjuvant treatment. We compared time to closure of ileostomy between two adjacent centres that share common stoma-care and oncology teams to see what benefit this policy provides. Patients were recruited over a 2-year period from 2005 to 2007 from two adjacent centres. Centre 1 had a policy to provide patients with a provisional date for closure of their ileostomy. The notes were studied retrospectively to determine time to closure of the ileostomy and reasons for any delays in closure. A total of 107 patients fulfilled the inclusion criteria, of which 83 patients (72%) had their stomas closed. Thirty patients had their stomas closed within 12 weeks (37%) - more than 67% (23/34) in centre 1 against 15% (7/48) in centre 2. At 1 year, all patients in centre 1 had their ileostomy closed, while 10% (5/48) were still waiting in centre 2. The mean time to closure was 13.47 and 25.25 weeks for centres 1 and 2 respectively -P-value < 0.0001. Offering patients a date for ileostomy closure at discharge from their primary resection results in the majority of stomas being closed within 12 weeks. For those patients who are to undergo adjuvant chemotherapy, we aim to perform this surgery in between the second and third cycles of treatment.

A description of the origins, design and performance of the TRAITS-SGP Atlantic salmon Salmo salar L. cDNA microarray.

The origins, design, fabrication and performance of an Atlantic salmon microarray are described. The microarray comprises 16 950 Atlantic salmon-derived cDNA features, printed in duplicate and mostly sourced from pre-existing expressed sequence tag (EST) collections [SALGENE and salmon genome project (SGP)] but also supplemented with cDNAs from suppression subtractive hybridization libraries and candidate genes involved in immune response, protein catabolism, lipid metabolism and the parr-smolt transformation. A preliminary analysis of a dietary lipid experiment identified a number of genes known to be involved in lipid metabolism. Significant fold change differences (as low as 1.2x) were apparent from the microarray analysis and were confirmed by quantitative real-time polymerase chain reaction analysis. The study also highlighted the potential for obtaining artefactual expression patterns as a result of cross-hybridization of similar transcripts. Examination of the robustness and sensitivity of the experimental design employed demonstrated the greater importance of biological replication over technical (dye flip) replication for identification of a limited number of key genes in the studied system. The TRAITS (TRanscriptome Analysis of Important Traits of Salmon)-salmon genome project microarray has been proven, in a number of studies, to be a powerful tool for the study of key traits of Atlantic salmon biology. It is now available for use by researchers in the wider scientific community.

Colorectal tubulovillous adenomas identified on fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography scans.

OBJECTIVE: The aim of this retrospective study was to assess the significance of incidental focal colonic lesions on fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG PET/CT) scans in patients undergoing staging for noncolorectal cancer. METHOD: Of the 110 patients in our PET/CT database, 10 were found to have abnormally high uptake of tracer in their large bowel. RESULTS: Seven patients who underwent further endoscopic evaluation of these abnormalities had intermediate to high-risk adenomatous polyps. CONCLUSION: Benign colonic polyps produce high-intensity focal FDG uptake in large bowel. Endoscopic evaluation is recommended before curative resectional surgery of the presenting cancer where appropriate.

Should indeterminate lung lesions reported on staging CT scans influence the management of patients with colorectal cancer?

OBJECTIVE: The aim of this study was to determine the significance of indeterminate lung lesions reported from staging CT scans on patients with colorectal cancer. METHOD: CT-scan reports of 439 patients were reviewed to identify patients in which indeterminate lung lesion had been reported. The tumour, node, metastasis (TNM) stage of these patients was recorded together with any follow-up scan reports or multidisciplinary team (MDT) discussions regarding these lesions. RESULTS: Twenty-three patients had definite lung metastases. Forty-five patients had indeterminate lung lesions. Of these, 22 patients had N1 or N2 disease, 20 had N0 disease and three patients were not operated on due to comorbidity. Of these 45 patients, 30 had further follow-up scans. In 19, the indeterminate lesions were unchanged and were therefore downgraded to benign lesions. The lesions had progressed or new lesions had developed in five. These patients were therefore shown to have metastatic lung disease. All five of these patients had N1 or N2 disease. One patient had a primary rather than metastatic lung lesion. Follow-up scans showed the lesion to be no longer present in five. Of the remainder, One patient declined further follow up. Three patients did not have a follow up scan for reasons not mentioned in their records. Two patients were not scanned because further MDT review of the original scans showed that the lesions were not metastases. Four patients died before follow up scans were done. (one postoperative myocardial infarction (MI), one postoperative sepsis, one postoperative cerebrovascular accident (CVA) and one inferior vena cava (IVC) obstruction). Five patients have not yet had follow-up scan at the time of writing. CONCLUSION: Since the introduction of spiral CT scanners, smaller lesions are being seen at the time of preoperative staging. Our study concludes that only a small proportion of indeterminate lung lesions did develop into definite metastases and those that did had node positive disease. Indeterminate lung lesions are not a reason to delay surgery for colorectal cancer.

Interferon type I and type II responses in an Atlantic salmon (Salmo salar) SHK-1 cell line by the salmon TRAITS/SGP microarray.

Interferons (IFNs) are cytokines that have proinflammatory, antiviral, and immunomodulatory effects and play a central role during a host response to pathogens. The IFN family contains both type I and type II molecules. While there are a number of type I IFNs, there is only one type II IFN. Recently both type I and type II IFN genes have been cloned in salmonid fish and recombinant proteins produced showing IFN activity. We have stimulated an Atlantic salmon cell line (SHK-1) with both type I and type II recombinant salmonid IFNs and analyzed the transcriptional response by microarray analysis. Cells were exposed to recombinant IFNs for 6 or 24 h or left unexposed as controls. RNA was hybridized to an Atlantic salmon cDNA microarray (salmon 17K feature TRAITS/SGP array) in order to assess differential gene expression in response to IFN exposure. For IFN I and II, 47 and 72 genes were stimulated, respectively; most genes were stimulated by a single IFN type, but some were affected by both IFNs, indicating coregulation of the IFN response in fish. Real-time PCR analysis was employed to confirm the microarray results for selected differentially expressed genes in both a cell line and primary leukocyte cultures.

Local control of light polarization with low-temperature fiber optics.

A fiber-optic-based polarization control system that uses a backreflection measurement scheme at low temperatures has been developed. This provides a stringent test of the light polarization state at the output of the fiber, allowing for determination and control of the degree of circular polarization; i.e., it can generate linear, right, or left circular polarization with cryogenic fibers. This polarization controller is paving the way toward the control and manipulation of nuclear spins in semiconductors via the optical Overhauser effect and could be used, for example, for the purpose of quantum information processing with the large nuclear spins of GaAs.

Effects of sequential changes from conventional ventilation to high-frequency oscillatory ventilation at increasing mean airway pressures in an ovine model of combined lung and head injury.

BACKGROUND: The objective of this study was to determine the intracranial, cardiovascular and respiratory changes induced by conversion to high-frequency oscillator ventilation from conventional mechanical ventilation at increasing airway pressures. METHODS: In this study, 11 anaesthetized sheep had invasive cardiovascular and intracranial monitors placed. Lung injury was induced by saline lavage and head injury was induced by inflation of an intracranial balloon catheter. All animals were sequentially converted from conventional mechanical ventilation to high-frequency oscillator ventilation at target mean airway pressures of 16, 22, 28, 34 and 40 cm H(2)O. The mean airway pressure was achieved by adjusting positive end expiratory pressure while on conventional mechanical ventilation, and continuous distending pressures while on high-frequency oscillator ventilation. Cerebral lactate production, oxygen consumption and venous oximetry were measured and analysed in relation to changes in transcranial Doppler flow velocity. Transcranial Doppler profiles together with other physiological parameters were measured at each airway pressure. RESULTS: Cerebral perfusion pressure was significantly lower during high-frequency oscillator ventilation than during conventional mechanical ventilation (CMV: 45, 34, 22, 6, 9 mmHg vs. HFOV: 33, 20, 19, 5, 5 mmHg at airway pressures mentioned above, P = 0.02). Intracranial pressure and cerebrovascular resistance increased with increasing intrathoracic pressures (P = 0.001). Cerebral metabolic indices demonstrated an initial increase in anaerobic metabolism followed by a decrease in cerebral oxygen consumption progressing to cerebral infarction as intrathoracic pressures were further increased in a stepwise fashion. Arterial PaCO(2) increased significantly after converting from conventional mechanical ventilation to high-frequency oscillator ventilation (P = 0.001). However, no difference was observed between conventional mechanical ventilation and high-frequency oscillator ventilation when intracranial pressure, metabolic and transcranial Doppler indices were compared at equivalent mean airway pressures. CONCLUSIONS: The use of high positive end expiratory pressure with conventional mechanical ventilation or high continuous distending pressure with high-frequency oscillator ventilation increased intracranial pressure and adversely affected cerebral metabolic indices in this ovine model. Transcranial Doppler is a useful adjunct to intracranial pressure and intracranial venous saturation monitoring when major changes in ventilation strategy are adopted.

Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists.

To investigate the relationship between survival in colorectal cancer patients and the number of lymph nodes examined by a pathologist, previously attributed to stage migration, we used data from a cohort of 5174 colorectal cancer patients recruited between September 1991 and August 1994, and followed-up for 5 years. We selected cases with data present on all prognostic variables, and stratified them into three groups by number of nodes examined. We made a multivariate survival comparison using a Cox regression model. In all, there were 3592 cases with data present on all prognostic variables. Patients who had >10 nodes identified had a significant survival advantage over those who had 5-10 identified, who had in turn a similar advantage over those with 0-4 identified (P<0.001). This effect was present in the whole group and at all Dukes' stages, although statistically significant only in stages B (P=0.004) and C (P=0.019). The effect remained after adjustment in a Cox regression model in which the mean number of nodes taken out by each surgical firm did not predict survival. In a sub-group with data on lymphocytic infiltration into the primary tumour a survival advantage was noted in those with prominent rather than mild infiltration (P<0.001): the former also tended to have more nodes found (P=0.015). Stage migration alone cannot explain these results, as survival advantages are noted across the whole population independent of stage. Lymphocytic infiltration into the primary tumour is prognostically important, and is associated with the number of nodes found. Reactive enlargement of lymph nodes in the mesentery may make them easier to find, reflect immune response to the tumour, and thus indirectly impact upon survival.