Comparison of multimodal analgesia with thoracic epidural after transthoracic oesophagectomy.

BACKGROUND: Thoracic epidural analgesia (TEA) has been regarded as the standard of care after oesophagectomy for pain control, but has several side-effects. Multimodal (intrathecal diamorphine, paravertebral and rectus sheath catheters) analgesia (MA) may facilitate postoperative mobilization by reducing hypotensive episodes and the need for vasopressors, but uncertainty exists about whether it provides comparable analgesia. This study aimed to determine whether MA provides comparable analgesia to TEA following transthoracic oesophagectomy. METHODS: Consecutive patients undergoing oesophagectomy for cancer between January 2015 and December 2018 were grouped according to postoperative analgesia regimen. Propensity score matching (PSM) was used to account for treatment selection bias. Pain scores at rest and on movement, graded from 0 to 10, were used. The incidence of hypotensive episodes and the requirement for vasopressors were evaluated. RESULTS: The study included 293 patients; 142 (48.5 per cent) received TEA and 151 (51.5 per cent) MA. After PSM, 100 patients remained in each group. Mean pain scores were significantly higher at rest in the MA group (day 1: 1.5 versus 0.8 in the TEA group, P = 0.017; day 2: 1.7 versus 0.9 respectively, P = 0.014; day 3: 1.2 versus 0.6, P = 0.047). Fewer patients receiving MA had a hypotensive episode (25 per cent versus 45 per cent in the TEA group; P = 0.003) and fewer required vasopressors (36 versus 53 per cent respectively; P = 0.016). There was no significant difference in the overall complication rate (71.0 versus 61.0 per cent; P = 0.136). CONCLUSION: MA is less effective than TEA at controlling pain, but this difference may not be clinically significant. However, fewer patients experienced hypotension or required vasopressor support with MA; this may be beneficial within an enhanced recovery programme.

A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer.

BACKGROUND: The optimal duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer patients is unknown, with 5, 7 or 10 days being commonly prescribed. This trial evaluates whether 5 days of filgrastim was non-inferior to 7/10 days. PATIENTS AND METHODS: In this randomised, open-label trial, early breast cancer patients who were to receive filgrastim as primary FN prophylaxis were randomly allocated to 5 versus 7 versus 10 days of filgrastim for all chemotherapy cycles. A protocol amendment in November 2017 allowed subsequent patients (N = 324) to be randomised to either 5 or 7/10 days. The primary outcome was a composite of either FN or treatment-related hospitalisations. Secondary outcomes included chemotherapy dose reductions, delays and discontinuations. Analyses were carried out by per protocol (primary) and intention-to-treat, and the non-inferiority margin was set at 3% for the risk of having FN and/or hospitalisation per cycle of chemotherapy. RESULTS: Patients (N = 466) were randomised to receive 5 (184, 39.5%), or 7/10 (282, 60.5%) days of filgrastim. In our primary analysis, the difference in risk of either FN or treatment-related hospitalisation per cycle was -1.52% [95% confidence interval (CI): -3.22% to 0.19%] suggesting non-inferiority of a 5-day filgrastim schedule compared with 7/10-days. The difference in events per cycle for FN was 0.11% (95% CI: -1.05 to 1.27) while for treatment-related hospitalisations it was -1.68% (95% CI: -2.73% to -0.63%). The overall proportions of patients having at least one occurrence of either FN or treatment-related hospitalisation were 11.8% and 14.96% for the 5- and 7/10-day groups, respectively (risk difference: -3.17%, 95% CI: -9.51% to 3.18%). CONCLUSION: Five days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days should be considered standard of care. CLINICALTRIALS. GOV REGISTRATION: NCT02428114 and NCT02816164.

Optimal Coherent Filtering for Single Noisy Photons.

We introduce a filter using a noise-free quantum buffer with large optical bandwidth that can both filter temporal-spectral modes as well as interconvert them and change their frequency. We theoretically show that such quantum buffers optimally filter out temporal-spectral noise, producing identical single photons from many distinguishable noisy single-photon sources with the minimum required reduction in brightness. We then experimentally demonstrate a noise-free quantum buffer in a warm atomic system that is well matched to quantum dots. Based on these experiments, simulations show that our buffer can outperform all intensity (incoherent) filtering schemes for increasing indistinguishability.

How confident are general practitioners in interpreting neuroradiology reports?

AIM: To determine the level of confidence general practitioners (GPs) have in radiology reports provided by neuroradiologists and to elicit the preferences of GPs regarding report format and level of detail. MATERIALS AND METHODS: Electronic surveys comprising anonymised neuroradiology reports were sent to GP practices served by a tertiary neuroscience centre. After reviewing the reports, GPs were asked to complete a two-part questionnaire. Firstly, GPs indicated their level of confidence, using a five-tiered Likert scale, in their understanding of: (a) the body of text; (b) the meaning of the report; and (c) the significance of the report. Secondly, GPs provided free-text suggestions for improving the report and highlighted any phrases that they did not understand. RESULTS: One hundred GPs responded from a group of 439 that received a survey (response rate 23%). Although the majority of GPs were fairly confident in their understanding of reports, fewer than one-third of GPs were entirely confident. Approximately 10% of GPs were not confident at all in their understanding of the reports. Causes of confusion included the use of detailed anatomy, acronyms, radiological terminology, and a lack of a conclusion and an action plan. CONCLUSION: General practice is a time-sensitive discipline that demands clear communication. In neuroradiology reports, GPs do not find detailed anatomy, acronyms, or radiological terminology helpful. Rather, GPs want a clear conclusion and action plan.

Activity behaviors in lean and morbidly obese pregnant women.

Interventions to increase physical activity in pregnancy are challenging for morbidly obese women. Targeting sedentary behaviors may be a suitable alternative to increase energy expenditure. We aimed to determine total energy expenditure, and energy expended in sedentary activities in morbidly obese and lean pregnant women. We administered the Pregnancy Physical Activity Questionnaire (nonobjective) and the Actical accelerometer (objective) to morbidly obese (BMI ≥ 40 kg/m²) and lean (BMI ≤ 25 Kg/m²) pregnant women recruited in early (<24 weeks), and late (≥24 weeks) gestation. Data are mean (SD). Morbidly obese pregnant women reported expending significantly more energy per day in early (n = 140 vs 109; 3198.4 (1847.1) vs 1972.3 (10284.8) Kcal/d, P < .0001) and late (n = 104 vs 64; 3078.2 (1356.5) vs 1947.5 (652.0) Kcal/d, P < .0001) pregnancy, and expended significantly more energy in sedentary activities, in early (816.1 (423.5) vs 540.1 (244.9) Kcal/d, P < .0001) and late (881.6 (455.4) vs 581.1 (248.5) Kcal/d, P < .0001) pregnancy, than lean pregnant women. No differences were observed in the proportion of energy expended sedentary between lean and morbidly obese pregnant women. The greater total energy expenditure in morbidly obese pregnant women was corroborated by Actical accelerometer in early (n = 14 per group, obese 1167.7 (313.6) Kcal; lean 781.1 (210.1) Kcal, P < .05), and in late (n = 14 per group, obese 1223.6 (351.5) Kcal; lean 893.7 (175.9) Kcal, P < .05) pregnancy. In conclusion, non-objective and objective measures showed morbidly obese pregnant women expended more energy per day than lean pregnant. Further studies are needed to determine whether sedentary behaviors are a suitable target for intervention in morbidly obese pregnancy.

Multimodal analgesia using intrathecal diamorphine, and paravertebral and rectus sheath catheters are as effective as thoracic epidural for analgesia post-open two-phase esophagectomy within an enhanced recovery program.

Thoracic epidural (TE) analgesia has been the standard of care for transthoracic esophagectomy patients since the 1990s. Multimodal anesthesia using intrathecal diamorphine, local anesthetic infusion catheters (LAC) into the paravertebral space and rectus sheaths and intravenous opioid postoperatively represent an alternative option for postoperative analgesia. While TE can provide excellent pain control, it may inhibit early postoperative recovery by causing hypotension and reducing mobilization. The aim of this study is to determine whether multimodal analgesia with LAC was effective with respect to adequate pain management, and compare its impact on hypotension and mobility. Patients receiving multimodal LAC analgesia were matched using propensity score matching to patients undergoing two-phase trans-thoracic esophagectomy with a TE over a two-year period (from January 2015 to December 2016). Postoperative endpoints that had been evaluated prospectively, including pain scores on movement and at rest, inotrope or vasoconstrictor requirements, and hypotension (systolic BP < 90 mmHg), were compared between cohorts. Out of 14 patients (13 male) that received LAC were matched to a cohort of 14 patients on age, sex, and comorbidity. Mean and maximum pain scores at rest and movement on postoperative days 0 to 3 were equivalent between the groups. In both cohorts, 50% of patients had a pain score of more than 7 on at least one occasion. Fewer patients in the LAC group required vasoconstrictor infusion (LAC: 36% vs. TE: 57%, P = 0.256) to maintain blood pressure or had episodes of hypotension (LAC: 43% vs. TE: 79%, P = 0.05). The LAC group was more able to ambulate on the first postoperative day (LAC: 64% vs. TE: 43%, P = 0.14) but these differences were not statistically significant. Within the epidural cohort, three patients had interruption of epidural due to dislodgement or failure of block compared to no disruption in the multimodal local anesthesia catheters group (P = 0.05). Therefore, multimodal anesthesia using spinal diamorphine with combined paravertebral and rectus sheath local anesthetic catheters appears to provide comparable pain relief post two-phase esophagectomy and may provide more reliable and safe analgesia than the current standard of care.

Disrupted nitric oxide signaling due to GUCY1A3 mutations increases risk for moyamoya disease, achalasia and hypertension.

Moyamoya disease (MMD) is a progressive vasculopathy characterized by occlusion of the terminal portion of the internal carotid arteries and its branches, and the formation of compensatory moyamoya collateral vessels. Homozygous mutations in GUCY1A3 have been reported as a cause of MMD and achalasia. Probands (n = 96) from unrelated families underwent sequencing of GUCY1A3. Functional studies were performed to confirm the pathogenicity of identified GUCY1A3 variants. Two affected individuals from the unrelated families were found to have compound heterozygous mutations in GUCY1A3. MM041 was diagnosed with achalasia at 4 years of age, hypertension and MMD at 18 years of age. MM149 was diagnosed with MMD and hypertension at the age of 20 months. Both individuals carry one allele that is predicted to lead to haploinsufficiency and a second allele that is predicted to produce a mutated protein. Biochemical studies of one of these alleles, GUCY1A3 Cys517Tyr, showed that the mutant protein (a subunit of soluble guanylate cyclase) has a significantly blunted signaling response with exposure to nitric oxide (NO). GUCY1A3 missense and haploinsufficiency mutations disrupt NO signaling leading to MMD and hypertension, with or without achalasia.

Cavity-Enhanced Room-Temperature Broadband Raman Memory.

Broadband quantum memories hold great promise as multiplexing elements in future photonic quantum information protocols. Alkali-vapor Raman memories combine high-bandwidth storage, on-demand readout, and operation at room temperature without collisional fluorescence noise. However, previous implementations have required large control pulse energies and have suffered from four-wave-mixing noise. Here, we present a Raman memory where the storage interaction is enhanced by a low-finesse birefringent cavity tuned into simultaneous resonance with the signal and control fields, dramatically reducing the energy required to drive the memory. By engineering antiresonance for the anti-Stokes field, we also suppress the four-wave-mixing noise and report the lowest unconditional noise floor yet achieved in a Raman-type warm vapor memory, (15±2)×10^{-3} photons per pulse, with a total efficiency of (9.5±0.5)%.

Diagnostic accuracy and limitations of post-mortem MRI for neurological abnormalities in fetuses and children.

AIM: To compare the diagnostic accuracy of non-invasive cerebral post-mortem magnetic resonance imaging (PMMRI) specifically for cerebral and neurological abnormalities in a series of fetuses and children, compared to conventional autopsy. MATERIALS AND METHODS: Institutional ethics approval and parental consent was obtained. Pre-autopsy cerebral PMMRI was performed in a sequential prospective cohort (n = 400) of fetuses (n = 277; 185 ≤ 24 weeks and 92 > 24 weeks gestation) and children <16 years (n = 123) of age. PMMRI and conventional autopsy findings were reported blinded and independently of each other. RESULTS: Cerebral PMMRI had sensitivities and specificities (95% confidence interval) of 88.4% (75.5 to 94.9), and 95.2% (92.1 to 97.1), respectively, for cerebral malformations; 100% (83.9 to 100), and 99.1% (97.2 to 99.7) for major intracranial bleeds; and 87.5% (80.1 to 92.4) and 74.1% (68 to 79.4) for overall brain pathology. Formal neuropathological examination was non-diagnostic due to maceration/autolysis in 43/277 (16%) fetuses; of these, cerebral PMMRI imaging provided clinically important information in 23 (53%). The sensitivity of PMMRI for detecting significant ante-mortem ischaemic injury was only 68% (48.4 to 82.8) overall. CONCLUSIONS: PMMRI is an accurate investigational technique for identifying significant neuropathology in fetuses and children, and may provide important information even in cases where autolysis prevents formal neuropathological examination; however, PMMRI is less sensitive at detecting hypoxic-ischaemic brain injury, and may not detect rarer disorders not encountered in this study.

Responsiveness of muscle size and strength to physical training in very elderly people: a systematic review.

The purpose of this review was to determine whether very elderly muscle (>75 years) hypertrophies in response to physical training. The databases MEDLINE; EMBASE; CINAHL Plus and SPORTDiscus were systematically literature searched with reference lists of all included studies and relevant reviews. Controlled trials (inactive elderly control group) involving healthy elderly participants over 75 years participating in an intervention complying with an established definition of physical training were included. Data extraction and quality assessment were performed using the PEDro scale. Data analysis was performed on muscle size and strength using RevMan (software version 5.1). Four studies were included of which four of four measured changes in gross muscle size. Training induced increases in muscle size from 1.5%-15.6% were reported in three of four studies, and one of four studies reported a decrease in muscle size (3%). The greatest gain in muscle mass was observed in a study of whole body vibration training. Meta-analysis of three studies found an increase of thigh muscle cross-sectional area (mean difference 2.31 cm(2) or 0.2%, 95% confidence interval (CI): 0.62 to 4.00; P = 0.008) and muscle strength (standardized mean difference 1.04, 95% CI: 0.65 to 1.43; P < 0.001). Physical training when delivered as resistance training has the ability to elicit hypertrophy and increase muscle strength in very elderly muscle.

Comparative effectiveness of interventions for cancer treatment-related cognitive impairment in adult cancer survivors: protocol for a systematic review.

BACKGROUND: Cancer treatment-related cognitive impairment (CTRCI) can substantially reduce the quality of life of cancer survivors. Many treatments of CTRCI have been evaluated in randomized controlled trials (RCTs), including psychological interventions, pharmacologic interventions, and other therapies. There is a pressing need to establish the benefits and harms of previously studied CTRCI treatments. The proposed systematic review and network meta-analyses will assess the relative efficacy and safety of competing interventions for the management of CTRCI. METHODS: In consultation with the review team, an experienced medical information specialist will draft electronic search strategies for MEDLINE®, Embase, CINAHL, PsycINFO, and the Cochrane Trials Registry. We will seek RCTs of interventions for the treatment of CTRCI in adults with any cancer, except cancers/metastases of the central nervous system. Due to the anticipated high search yields, dual independent screening of citations will be expedited by use of an artificial intelligence/machine learning tool. The co-primary outcomes of interest will be subjective and objective cognitive function. Secondary outcomes of interest will include measures of quality of life, mental and physical health symptoms, adherence to treatment, and harms (overall and treatment-related harms and harms associated with study withdrawal), where feasible, random-effects meta-analyses and network meta-analyses will be pursued. We will address the anticipated high clinical and methodological heterogeneity through meta-regressions, subgroup analyses, and/or sensitivity analyses. DISCUSSION: The proposed systematic review will deliver a robust comparative evaluation of the efficacy and safety of existing therapies for the management of CTRCI. These findings will inform clinical decisions, identify evidence gaps, and identify promising therapies for future evaluation in RCTs.

Pregnancy-specific anxiety, ART conception and infant temperament at 4 months post-partum.

STUDY QUESTION: Is anxiety focused on the pregnancy outcome, known to be particularly salient in women conceiving through assisted reproductive technology (ART), related to difficult infant temperament? SUMMARY ANSWER: While trait anxiety predicts infant temperament, pregnancy-focused anxiety is not associated with more difficult infant temperament. WHAT IS KNOWN ALREADY: A large body of research has provided convincing evidence that fetal exposure to maternal anxiety and stress in pregnancy has adverse consequences for child neurodevelopmental, behavioural and cognitive development, and that pregnancy-specific anxiety (concerns related to the pregnancy outcome and birth) may be of particular significance. Women conceiving through ART are of particular interest in this regard. Research over more than 20 years has consistently demonstrated that while they do not differ from spontaneously conceiving (SC) women with respect to general (state and trait) anxiety, they typically report higher pregnancy-specific anxiety. While research suggests normal behavioural and developmental outcomes for children conceived through ART, there is some evidence of more unsettled infant behaviour during the first post-natal year. STUDY DESIGN, SIZE, DURATION: The longitudinal cohort design followed 562 nulliparous women over a 7-month period, during the third trimester of pregnancy and at 4 months after birth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Approximately equal numbers of nulliparous women conceiving through ART (n = 250) and spontaneously (SC: n = 262) were recruited through ART clinics and nearby hospitals in Melbourne and Sydney, Australia. Participants completed three anxiety measures (state, trait, pregnancy specific) at time 1 in the third trimester of pregnancy and a measure of infant temperament at time 2, 4 months after birth. At time 1, relevant socio-demographic, pregnancy (maternal age, smoking, alcohol, medications, medical complications) information was recorded and at time 2, information regarding childbirth (gestation, infant birthweight, mode of delivery) and post-natal (concurrent mood) variables was recorded and controlled for in analyses. MAIN RESULTS AND THE ROLE OF CHANCE: In the third trimester of pregnancy, women conceiving through ART reported lower state and trait anxiety, but higher pregnancy-focused anxiety than their SC counterparts (all Ps < 0.05). Hierarchical regression analyses including mode of conception, all anxiety variables and relevant covariates indicated that while trait anxiety in pregnancy predicted more difficult infant temperament (P < 0.001), pregnancy specific and state anxiety did not. Mode of conception predicted infant temperament; with ART women reporting less difficult infant temperament (P < 0.001) than their SC counterparts. LIMITATIONS, REASONS FOR CAUTION: The major limitations in the study are the reliance on a self-report measure of infant temperament and the fact that the study did not assess quality of caregiving which may moderate the effect of pregnancy anxiety on infant temperament. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to our knowledge to prospectively examine the impact of gestational stress (pregnancy anxiety) on infant temperament in women conceiving through ART. Findings confirm existing research indicating that trait anxiety in pregnancy is associated with difficult infant temperament and suggest that pregnancy-specific anxiety (measured in the third trimester) is not implicated. These findings are reassuring for women conceiving through ART whose pregnancies may be characterized by particularly intense concerns about the wellbeing of a long sought after baby. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by a grant from the Australian Research Council (ARC) and in kind and financial contributions from IVF Australia and Melbourne. TRIAL REGISTRATION NUMBER: N/A.

Sensitive, microliter PCR with consensus degenerate primers for Epstein Barr virus amplification.

Sensitive identification of the etiology of viral diseases is key to implementing appropriate prevention and treatment. The gold standard for virus identification is the polymerase chain reaction (PCR), a technique that allows for highly specific and sensitive detection of pathogens by exponentially amplifying a specific region of DNA from as little as a single copy through thermocycling a biochemical cocktail. Today, molecular biology laboratories use commercial instruments that operate in 0.5-2 h/analysis using reaction volumes of 5-50 µL contained within polymer tubes or chambers. Towards reducing this volume and maintaining performance, we present a semi-quantitative, systematic experimental study of how PCR yield is affected by tube/chamber substrate, surface-area-to-volume ratio (SA:V), and passivation methods. We perform PCR experiments using traditional PCR tubes as well as using disposable polymer microchips with 1 µL reaction volumes thermocycled using water baths. We report the first oil encapsulation microfluidic PCR method without fluid flow and its application to the first microfluidic amplification of Epstein Barr virus using consensus degenerate primers, a powerful and broad PCR method to screen for both known and novel members of a viral family. The limit of detection is measured as 140 starting copies of DNA from a starting concentration of 3 × 10(5) copies/mL, regarded as an accepted sensitivity threshold for diagnostic purposes, and reaction specificity was improved as compared to conventional methods. Also notable, these experiments were conducted with conventional reagent concentrations, rather than commonly spiked enzyme and/or template mixtures. This experimental study of the effects of substrate, SA:V, and passivation, together with sensitive and specific microfluidic PCR with consensus degenerate primers represent advances towards lower cost and higher throughput pathogen screening.

The Patient's perspective: A review of the results from a radiotherapy patient experience survey in the North-West of England.

INTRODUCTION: A patient experience survey was undertaken for patients completing radiotherapy at the three Northwest of England Radiotherapy Providers. METHODS: A previously reported National Radiotherapy Patient Experience Survey was adapted and undertaken in the Northwest of England. Quantitative data was analysed to establish trends. Frequency distribution was applied to appraise the number of participants selecting each of the pre-determined responses. Thematic analysis of free text responses was conducted. RESULTS: The questionnaire received 653 responses from the 3 providers across seven departments. Thematic analysis revealed 3 themes; logistics, information and operational. CONCLUSION: The results indicate that the majority of patients are satisfied with their treatment and care. Patients' responses indicate areas for improvements. Expectancy theory states that an individual's satisfaction is related to the difference between expected service and the service received. Consequently, when reviewing services and developing improvement it is important to understand patients' expectations. This regional survey starts to capture what people receiving radiotherapy expect from the service and the professionals delivering their treatment. IMPLICATIONS FOR PRACTICE: This survey responses make a case for reviewing the information provision pre and post radiotherapy. This includes clarifying the understanding of consent for treatment including the intended benefits and potential late effects. There is an argument to offer information sessions prior to radiotherapy to achieve more relaxed and informed patients. A recommendation from this work is for the radiotherapy community undertake a national radiotherapy patient experience survey, facilitated via the 11 Radiotherapy ODNs. A national radiotherapy survey has multiple benefits to inform improvements in practice. This includes benchmarking services against national averages. This approach is aligned with the principles of the service specification in terms of reducing variation and increasing quality.

Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients.

Head and neck squamous cell carcinoma (HNSCC) patients treated with high-dose cisplatin concurrently with radiotherapy (hdCis-RT) commonly suffer kidney injury leading to acute and chronic kidney disease (AKD and CKD, respectively). We conducted a retrospective analysis of renal function and kidney injury-related plasma biomarkers in a subset of HNSCC subjects receiving hdCis-RT in a double-blinded, placebo-controlled clinical trial (NCT02508389) evaluating the superoxide dismutase mimetic, avasopasem manganese (AVA), an investigational new drug. We found that 90 mg AVA treatment prevented a significant reduction in estimated glomerular filtration rate (eGFR) three months as well as six and twelve months after treatment compared to 30 mg AVA and placebo. Moreover, AVA treatment may have allowed renal repair in the first 22 days following cisplatin treatment as evidenced by an increase in epithelial growth factor (EGF), known to aid in renal recovery. An upward trend was also observed in plasma iron homeostasis proteins including total iron (Fe-blood) and iron saturation (Fe-saturation) in the 90 mg AVA group versus placebo. These data support the hypothesis that treatment with 90 mg AVA mitigates cisplatin-induced CKD by inhibiting hdCis-induced renal changes and promoting renal recovery.

Plug-and-play, infrared, laser-mediated PCR in a microfluidic chip.

Microfluidic polymerase chain reaction (PCR) systems have set milestones for small volume (100 nL-5 µL), amplification speed (100-400 s), and on-chip integration of upstream and downstream sample handling including purification and electrophoretic separation functionality. In practice, the microfluidic chips in these systems require either insertion of thermocouples or calibration prior to every amplification. These factors can offset the speed advantages of microfluidic PCR and have likely hindered commercialization. We present an infrared, laser-mediated, PCR system that features a single calibration, accurate and repeatable precision alignment, and systematic thermal modeling and management for reproducible, open-loop control of PCR in 1 µL chambers of a polymer microfluidic chip. Total cycle time is less than 12 min: 1 min to fill and seal, 10 min to amplify, and 1 min to recover the sample. We describe the design, basis for its operation, and the precision engineering in the system and microfluidic chip. From a single calibration, we demonstrate PCR amplification of a 500 bp amplicon from λ-phage DNA in multiple consecutive trials on the same instrument as well as multiple identical instruments. This simple, relatively low-cost plug-and-play design is thus accessible to persons who may not be skilled in assembly and engineering.

Large outbreak of Salmonella enteritidis PT8 in Portsmouth, UK, associated with a restaurant.

Seventy-five individuals with Salmonella infection were identified in the Portsmouth area during August and September 2009, predominantly Salmonella Enteritidis phage type 8. Five patients were admitted to hospital. A case-case comparison study showed that a local restaurant was the most likely source of the infection with a risk of illness among its customers 25-fold higher than that of those who did not attend the restaurant. A case-control study conducted to investigate specific risk factors for infection at the restaurant showed that eating salad was associated with a threefold increase in probability of illness. Changing from using ready washed lettuces to lettuces requiring washing and not adhering strictly to the 48 hours exclusion policy for food handlers with diarrhoea were likely to have contributed to the initiation and propagation of this outbreak. Possibilities for cross-contamination and environmental contamination were identified in the restaurant.

Variations in mortality after emergency laparotomy: the first report of the UK Emergency Laparotomy Network.

BACKGROUND: Emergency laparotomy is a common intra-abdominal procedure. Outcomes are generally recognized to be poor, but there is a paucity of hard UK data, and reports have mainly been confined to single-centre studies. METHODS: Clinicians were invited to join an 'Emergency Laparotomy Network' and to collect prospective non-risk-adjusted outcome data from a large number of NHS Trusts providing emergency surgical care. Data concerning what were considered to be key aspects of perioperative care, including thirty-day mortality, were collected over a 3 month period. RESULTS: Data from 1853 patients were collected from 35 NHS hospitals. The unadjusted 30 day mortality was 14.9% for all patients and 24.4% in patients aged 80 or over. There was a wide variation between units in terms of the proportion of cases subject to key interventions that may affect outcomes. The presence of a consultant surgeon in theatre varied between 40.6% and 100% of cases, while a consultant anaesthetist was present in theatre for 25-100% of cases. Goal-directed fluid management was used in 0-63% of cases. Between 0% and 68.9% of the patients returned to the ward (level one) after surgery, and between 9.7% and 87.5% were admitted to intensive care (level three). Mortality rates varied from 3.6% to 41.7%. CONCLUSIONS: This study confirms that emergency laparotomy in the UK carries a high mortality. The variation in clinical management and outcomes indicates the need for a national quality improvement programme.

Germline mutations in CDH1 are infrequent in women with early-onset or familial lobular breast cancers.

BACKGROUND: Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer; lobular breast cancer also occurs excessively in families with such condition. METHOD: To determine if CDH1 is a susceptibility gene for lobular breast cancer in women without a family history of diffuse gastric cancer, germline DNA was analysed for the presence of CDH1 mutations in 318 women with lobular breast cancer who were diagnosed before the age of 45 years or had a family history of breast cancer and were not known, or known not, to be carriers of germline mutations in BRCA1 or BRCA2. Cases were ascertained through breast cancer registries and high-risk cancer genetic clinics (Breast Cancer Family Registry, the kConFab and a consortium of breast cancer genetics clinics in the United States and Spain). Additionally, Multiplex Ligation-dependent Probe Amplification was performed for 134 cases to detect large deletions. RESULTS: No truncating mutations and no large deletions were detected. Six non-synonymous variants were found in seven families. Four (4/318 or 1.3%) are considered to be potentially pathogenic through in vitro and in silico analysis. CONCLUSION: Potentially pathogenic germline CDH1 mutations in women with early-onset or familial lobular breast cancer are at most infrequent.

Surgical revascularisation for childhood moyamoya.

PURPOSE: Children with moyamoya disease/syndrome (MM) have a high rate of recurrent arterial ischaemic stroke (AIS) and associated neurological morbidity; surgical revascularisation (SR) has the potential to prevent this. Here we describe our experience of SR for childhood mm. METHODS: This study is a retrospective review of case notes and radiology of children with moyamoya who underwent SR at our centre. RESULTS: Seventy-three children with MM and who had SR were identified, with median age at presentation of 4.75 years (range 0.6-14.5). Children with >1 AIS or transient ischaemic attack (TIA) and who had not infarcted the whole territory of the diseased carotid artery were offered SR, with the primary aim of preventing further AIS. One hundred and thirty-four SR procedures were undertaken: 82 indirect (62.4 %) and 49 (37.6 %) direct procedures with 3 second SR procedures following initial SR. Median age at surgery was 7.3 (1-18.2) years. There was no perioperative mortality. One anticoagulated child developed an intracranial haemorrhage on the fifth post-operative day. Median duration of follow-up was 34 (5-166) months. Three children (4.1 %) had recurrent AIS (one silent) after SR; two with sickle cell disease had intracranial haemorrhage 1.5 and 11 months post-SR. TIAs improved in 42 out of 53 (79.2 %). CONCLUSION: Our experience of SR for paediatric MM is comparable to other large series. SR is safe, and the rate of recurrent AIS after SR is lower than would be anticipated, on the basis of known natural history of MM. There was no observed difference in outcome of recurrent AIS for direct versus indirect procedures in this series.