Mitigation measures against Coronavirus Disease 2019 (COVID-19) in overnight faith-based camps: summer 2021.

OBJECTIVE: In this study, we describe community-based nonpharmaceutical interventions (NPIs) incorporated into COVID-19 mitigation protocols, and SARS-CoV-2 incidence at five faith-based summer camps in the US. STUDY DESIGN: Retrospective cohort study. METHODS: Six southeastern states within the United States (13 sites) were assessed from May 30 to August 14, 2021 (13 sites; N = 13,132; May-August 2021). Camp mitigation policies and NPIs (including masking, vaccinations, meal arrangements, physical distancing, pre-arrival testing, symptom screening, quarantine/isolation, and ventilation upgrades), and SARS-CoV-2 infections were tracked at each site. RESULTS: The symptomatic primary case attack rate was 24.7 (range: 0.0-120.0) cases per 100,000 people per week. Fewer infections were observed in camps with greater mitigation protocols. CONCLUSION: These findings suggest that nonpharmaceutical mitigation can promote stable access to youth programs for historically vaccine-hesitant subgroups. Policy recommendations for nonpharmaceutical interventions to prevent respiratory viral transmission in overnight youth faith-based camp settings may include outdoor activities, accessible symptomatic tests, prearrival testing, indoor mask use, small cohorts, physical distancing, and protocols to minimize staff exposures during time off.

Evaluation of the Efficacy of Doxycycline, Ciprofloxacin, Levofloxacin, and Co-trimoxazole Using In Vitro and In Vivo Models of Q Fever.

Q fever, caused by the intracellular pathogen Coxiella burnetii, is traditionally treated using tetracycline antibiotics, such as doxycycline. Doxycycline is often poorly tolerated, and antibiotic-resistant strains have been isolated. In this study, we have evaluated a panel of antibiotics (doxycycline, ciprofloxacin, levofloxacin, and co-trimoxazole) against C. burnetii using in vitro methods (determination of MIC using liquid and solid media; efficacy assessment in a THP cell infection model) and in vivo methods (wax moth larvae and mouse models of infection). In addition, the schedule for antibiotic treatment has been evaluated, with therapy initiated at 24 h pre- or postchallenge. Both doxycycline and levofloxacin limited overt clinical signs during treatment in the AJ mouse model of aerosol infection, but further studies are required to investigate the possibility of disease relapse or incomplete bacterial clearance after the antibiotics are stopped. Levofloxacin was well tolerated and therefore warrants further investigation as an alternative to the current recommended treatment with doxycycline.

Evaporation and Electrowetting of Sessile Droplets on Slippery Liquid-Like Surfaces and Slippery Liquid-Infused Porous Surfaces (SLIPS).

Sessile droplet evaporation underpins a wide range of applications from inkjet printing to coating. However, drying times can be variable and contact-line pinning often leads to undesirable effects, such as ring stain formation. Here, we show voltage programmable control of contact angles during evaporation on two pinning-free surfaces. We use an electrowetting-on-dielectric approach and Slippery Liquid-Infused Porous (SLIP) and Slippery Omniphobic Covalently Attached Liquid-Like (SOCAL) surfaces to achieve a constant contact angle mode of evaporation. We report evaporation sequences and droplet lifetimes across a broad range of contact angles from 105°-67°. The values of the contact angles during evaporation are consistent with expectations from electrowetting and the Young-Lippman equation. The droplet contact areas reduce linearly in time, and this provides estimates of diffusion coefficients close to the expected literature value. We further find that the total time of evaporation over the broad contact angle range studied is only weakly dependent on the value of the contact angle. We conclude that on these types of slippery surfaces, droplet lifetimes can be predicted and controlled by the droplet's volume and physical properties (density, diffusion coefficient, and vapor concentration difference to the vapor phase) largely independent of the precise value of contact angle. These results are relevant to applications, such as printing, spraying, coating, and other processes, where controlling droplet evaporation and drying is important.

Chair based exercise in community settings: a cluster randomised feasibility study.

BACKGROUND: Some older people who find standard exercise programmes too strenuous may be encouraged to exercise while remaining seated - chair based exercises (CBE). We previously developed a consensus CBE programme (CCBE) following a modified Delphi process. We firstly needed to test the feasibility and acceptability of this treatment approach and explore how best to evaluate it before undertaking a definitive trial. METHODS: A feasibility study with a cluster randomised controlled trial component was undertaken to 1. Examine the acceptability, feasibility and tolerability of the intervention and 2. Assess the feasibility of running a trial across 12 community settings (4 day centres, 4 care homes, 4 community groups). Centres were randomised to either CCBE, group reminiscence or usual care. Outcomes were collected to assess the feasibility of the trial parameters: level of recruitment interest and eligibility, randomisation, adverse events, retention, completion of health outcomes, missing data and delivery of the CCBE. Semi- structured interviews were conducted with participants and care staff following the intervention to explore acceptability. RESULTS: 48% (89 out of 184 contacted) of eligible centres were interested in participating with 12 recruited purposively. 73% (94) of the 128 older people screened consented to take part with 83 older people then randomised following mobility testing. Recruitment required greater staffing levels and resources due to 49% of participants requiring a consultee declaration. There was a high dropout rate (40%) primarily due to participants no longer attending the centres. The CCBE intervention was delivered once a week in day centres and community groups and twice a week in care homes. Older people and care staff found the CCBE intervention largely acceptable. CONCLUSION: There was a good level of interest from centres and older people and the CCBE intervention was largely welcomed. The trial design and governance procedures would need to be revised to maximise recruitment and retention. If the motivation for a future trial is physical health then this study has identified that further work to develop the CCBE delivery model is warranted to ensure it can be delivered at a frequency to elicit physiological change. If the motivation for a future trial is psychological outcomes then this study has identified that the current delivery model is feasible. TRIAL REGISTRATION: ISRCTN27271501 . Date registered: 30/01/2018.

An approach on defining competency in evidence-based dentistry.

INTRODUCTION: Assessment of evidence-based dentistry (EBD) knowledge and behaviour is hampered by lack of explicit competency criteria. This void impedes instructional design and assessment of student growth during the educational process. METHODS: Knowledge and cognitive domains supporting educational objectives in a pre-doctoral dental programme were identified for each level of the EBD five-step process. We articulated educational objectives with behavioural expectations for each level of skill acquisition at each step of the EBD process. Outcome evaluation criteria identify students' progressive level of skill acquisition from novice to expert. RESULTS: The educational objectives, type of knowledge, and nature of the cognitive process supporting these objectives are presented for each step of the EBD process. For example, educational objectives of the "Ask" step include (i) to construct a question from the patient presentation and knowledge limitations that addresses the clinical problem and (ii) to articulate the Problem, Intervention/Exposure, Comparison, Outcome (PICO) components. Achievement of these objectives requires both factual information regarding the PICO format and the cognitive process of understanding. Educational outcome criteria consistent with a competent clinician include clear articulation of the PICO with identifiable pieces that relate to the clinical situation. DISCUSSION: Assessment strategies for progression towards EBD competency are limited due to the complexity associated with evaluating EBD knowledge and behaviours. To evaluate performance, the EBD academic community must define competency expectations for entry into unsupervised general dental practice. CONCLUSION: This framework offers measurable outcome evaluation criteria to initiate a conversation with academic peers regarding current gaps in EBD assessment.

Evidence-based dentistry skill acquisition by second-year dental students.

INTRODUCTION: Identification and assessment of Evidence-based dentistry (EBD) outcomes have been elusive. Our objective was to describe EBD skill acquisition during the second (D2) year of pre-doctoral dental education and student competency at the end of the year. METHODS: The first and fourth (final) curricular-required EBD Exercises (ie, application of the first 4 steps of the 5-Step evidence-based practice process applied to a real or hypothetical situation) completed by D2 students (n = 151) during 2014-2015 and 2015-2016 were evaluated to measure skill acquisition through use of a novel rubric with measures of performance from novice to expert. Exercises were evaluated on the performance for each step, identification of manuscript details and reflective commentary on manuscript components. Changes in performance were evaluated using the chi-square test for trend and the Wilcoxon signed-rank test. RESULTS: Seventy-eight per cent of students scored competent or higher on the Ask step at the beginning of the D2 year; scores improved with 58% scoring proficient or expert on the fourth Exercise (P < .001). Most students were advanced beginners or higher in the Acquire, Appraise and Apply steps at the beginning of the D2 year, with minimal growth observed during the year. Identification of manuscript details improved between the first and fourth Exercises (P = .015); however, depth of commentary skills did not change. DISCUSSION: Unlike previous investigations evaluating EBD knowledge or behaviour in a testing situation, we evaluated skill acquisition using applied Exercises. CONCLUSION: Consistent with their clinical and scientific maturity, D2 students minimally performed as advanced beginners at the end of their D2 year.

Adolescent preferences and reactions to language about body weight.

Over 30% of youth and adolescents have overweight or obesity, and health care providers are increasingly discussing weight-based health with these patients. Stigmatizing language in provider-patient communication about obesity is well documented and could be particularly detrimental to youth and adolescents. Although some research has examined preferences for weight-based terminology among adults, no studies have addressed these issues in youth populations. This study represents a preliminary and systematic investigation of weight-based language preferences among adolescents with overweight and obesity enrolled in a summer weight loss camp. Participants (N=50) indicated preferences for weight-based language and emotional responses to words that their family members used in reference to their body weight. Weight neutral terminology ('weight', 'body mass index') were most preferred, although some differences in word preferences emerged by the participants' gender. Boys preferred having their weight described as 'overweight' and 'heavy', while girls preferred the word 'curvy'. A large proportion of participants, particularly girls, reported experiencing sadness, shame, and embarrassment if parents used certain words to describe their body weight, which highlights the importance of considering the emotional impact of weight-based terminology. Providers may consider asking youth and adolescents for their preferences when discussing weight-based health.

Evidence-based dentistry: assessment to document progression to proficiency.

INTRODUCTION: The integration of evidence-based dentistry (EBD) into pre-doctoral dental curricula requires the identification of desired outcomes, development of curricular content and design of assessment strategies which guide student performance whilst documenting achievement of desired curricular outcomes. Models for developing EBD curriculums have been described in the literature; however, the logistics of designing assessment instruments to progressively document student performance have received less attention. The objective of this article is to describe the University of Iowa's College of Dentistry's development and implementation of assessment strategies to guide student learning of EBD knowledge, application and assimilation to serve as a model for other institutions developing EBD assessment protocols. ASSESSMENT DEVELOPMENT: Desired EBD knowledge and behaviour outcomes guided the development of curricular content and progressive formative and summative assessment strategies. Vertically and horizontally integrated educational activities enabling students to demonstrate EBD knowledge whilst modelling desired behaviours were identified, whilst assessment principles guided development of learning guides and assessment instruments to document achievement of desired outcomes. Consistent EBD language and educational activities are utilised throughout the 4-year interdisciplinary curriculum with stepwise assessment protocols matched to the curriculum. Examples of student learning guides and assessment instruments are provided. SUMMARY: Curricular design guides development of assessment strategies. Assessment protocols provide consistent formative and summative feedback to enable continuous student growth to become proficient EBD practitioners.

Time-lapse in the IVF-lab: how should we assess potential benefit?

Time-lapse imaging of embryos has been widely introduced to fertility laboratories worldwide with the aim of identifying the best quality embryos to transfer that will ultimately improve IVF success rates. In this opinion paper, we explore the lack of evidence of benefit of this novel intervention, analyse the methodological flaws of current studies, offer ideal study designs that assess the various features of time-lapse imaging, and discuss forthcoming studies. In particular, we emphasize the ethical aspects of hastily adopting a costly technology without current high level evidence of improved live birth rates, safety and cost effectiveness.

Meiotic chromosome synapsis and recombination in Arabidopsis thaliana: new ways of integrating cytological and molecular approaches.

Meiosis is an evolutionary conserved mechanism that produces haploid gametes and is essential for the sexual reproduction of higher eukaryotes. Since the late nineteenth century, meiosis has been studied in plants due their large chromosomes compared with other organisms and due to advances in microscopy and cytological approaches. On the other hand, non-plant model organisms like budding yeast have been widely used recently in order to characterise the molecular and functional aspects of meiosis. Arabidopsis arose as a new meiotic model for plants during the last decade of the twentieth century. This emergence was sustained by different molecular and genetic advances, mainly by completing the full genome sequence in 2000. Since then, further development of molecular technologies and the cytological methodologies to analyse the meiotic dynamics in Arabidopsis have permitted researchers to establish plant meiosis at the forefront of international research. Some key plant meiotic recombination events have been established in Arabidopsis. These advances have placed researchers into the position to transfer their knowledge from this plant meiotic model to crops and are likely to have an impact on plant breeding and the development of agriculture in future years.

The effect of serial in vitro haemodilution with maternal cerebrospinal fluid and crystalloid on thromboelastographic (TEG(®) ) blood coagulation parameters, and the implications for epidural blood patching.

Epidural blood patches may be used to treat post-dural puncture headache following accidental dural puncture in parturients. Their mode of action and the optimum volume of blood for injection remain controversial, with the interaction between injected blood and cerebrospinal fluid unknown. We aimed to establish the effects of serial haemodilution of whole blood with cerebrospinal fluid from 34 pregnant patients compared with serial haemodilution with Hartmann's solution, using the thromboelastogram. Haemodilution with either cerebrospinal fluid or Hartmann's solution had significant procoagulant and clot destabilising effects, enhanced with progressive haemodilution up to 30%. The effect of cerebrospinal fluid was greater compared with Hartmann's solution (p < 0.001). Cerebrospinal fluid led to a mean (95% CI) decrease in r-time by 2.4 (1.6-3.2) min, a decrease in k-time by 0.6 (0.4-0.8) min, an increase in alpha angle by 7.3 (5.5-9.0)°, and a decrease in maximum amplitude by 2.0 (0.6-3.4) mm. This may have implications for epidural blood patch, as success may be reduced near the time of dural puncture when cerebrospinal fluid leak is at its greatest, and large volumes of blood may be required to reduce haemodilution and clot destabilisation by cerebrospinal fluid. In addition, blood patching should be performed at the level of the dural puncture in order to ensure that the maximum volume of blood comes into contact with the cerebrospinal fluid.

Effect of replacing alfalfa with panicled-tick clover or sericea lespedeza in corn-alfalfa-based substrates on in vitro ruminal methane production.

Methane emissions from ruminant livestock contribute to total anthropogenic greenhouse gas emissions and reduce metabolizable energy intake by the animal. Condensed tannins (CT) are polyphenolic plant secondary compounds commonly produced by some perennial forage legumes that characteristically bind to protein, carbohydrates, and minerals. The degree to which CT may affect ruminant nutrition depends upon the concentration, structural composition, and biological activity of the CT. The objective of our experiment was to determine the effect of replacing alfalfa in a corn-alfalfa-based substrate with a legume containing CT on in vitro CH4 production and the dynamics of fermentation using an in vitro gas production technique. All fermented substrates contained 50% ground corn as the energy concentrate portion, whereas the forage portion (50%) of each diet was comprised of alfalfa (control) or some combination of alfalfa and sericea lespedeza (SL) or panicled-tick clover (PTC). Our treatments consisted of PTC or SL 15, 30, and 45, which corresponded with 15, 30, or 45% replacement of the diet (alfalfa component) with either PTC or SL. Substrates containing 45% PTC or SL reduced in vitro CH4 production. Treatments did not affect total gas production as compared with that of the control. Replacement of alfalfa with SL or PTC increased fermentable organic matter (FOM). The PTC treatment increased FOM by as much as 1.8% at the 45% replacement level, whereas FOM of SL 45 was increased by less than 1%. The replacement of alfalfa with PTC increased substrate nutritive value greater than replacement with SL. There were no correlations between any physicochemical constituent of the substrates and CH4 production. A combination of factors associated with the inclusion of PTC and SL contributed to the in vitro CH4 production, and CT in these forages was likely a major contributing factor. Further confirmation of these results on in situ or in vivo animal systems is required. If proven effective in an in vivo production scenario, replacement of commonly fed non-CT-containing legumes, such as alfalfa, with legumes containing CT might be a viable method to decrease the effect of animal agriculture on greenhouse gas production.

Efficacy of liposome-encapsulated ciprofloxacin in a murine model of Q fever.

Encapsulation of antibiotics may improve treatment of intracellular infections by prolonging antibiotic release and improving antibiotic uptake into cells. In this study, liposome-encapsulated ciprofloxacin for inhalation (CFI) was evaluated as a postexposure therapeutic for the treatment of Coxiella burnetii, the causative agent of Q fever. Intranasal treatment of male A/Jola (A/J) mice with CFI (50 mg/kg of body weight) once daily for 7 days protected mice against weight loss and clinical signs following an aerosol challenge with C. burnetii. In comparison, mice treated twice daily with oral ciprofloxacin or doxycycline (50 mg/kg) or phosphate-buffered saline (PBS) lost 15 to 20% body weight and exhibited ruffled fur, arched backs, and dehydration. Mice were culled at day 14 postchallenge. The weights and bacterial burdens of organs were determined. Mice treated with CFI exhibited reduced splenomegaly and reduced bacterial numbers in the lungs and spleen compared to mice treated with oral ciprofloxacin or doxycycline. When a single dose of CFI was administered, it provided better protection against body weight loss than 7 days of treatment with oral doxycycline, the current antibiotic of choice to treat Q fever. These data suggest that CFI has potential as a superior antibiotic to treat Q fever.

Sleep disruption in tetraplegia: a randomised, double-blind, placebo-controlled crossover trial of 3 mg melatonin.

STUDY DESIGN: Randomised, double-blind, placebo-controlled crossover trial of melatonin supplementation to people with complete tetraplegia. OBJECTIVES: To investigate the effect that 3 mg melatonin supplementation has on objective and subjective sleep, quality of life and mood of people living with complete tetraplegia. SETTING: Austin Hospital Sleep Laboratory and participants' homes, Melbourne, Victoria, Australia. METHODS: Two week run-in followed by 3 week nightly administration of 3 mg melatonin or placebo, 2-week washout and further 3 week administration of the opposite treatment. Four testing sessions were conducted; the last nights of the run-in, treatment and washout periods. Testing sessions involved recording full polysomnography, completing a questionnaire battery and collecting urine and blood samples. The questionnaires assessed mood, sleep symptoms and health-related quality of life, and the urine and plasma samples assayed 6-sulphatoxymelatonin (aMT6s) and melatonin levels, respectively. A sleep diary was completed throughout the study. RESULTS: Eight participants (mean (s.d.): age 49.5 years (16), postinjury 16.9 years (7.1)) were recruited in which seven concluded the protocol. Endogenous-circulating melatonin was significantly higher (P < or = 0.01) following melatonin (urine: 152.94 µg h(-1) (74.51), plasma: 43,554.57 pM (33,527.11)) than placebo (urine: 0.86 µg h(-1) (0.40), plasma: 152.06 pM (190.55)). Subjective sleep improved significantly following melatonin specifically for duration of sleep per night and psychological wellbeing. Objective sleep showed a significant increase in light sleep with melatonin, with all other sleep parameters being unchanged. CONCLUSION: These results suggest that increasing melatonin in people with complete tetraplegia is beneficial, especially for subjective sleep. Investigation of the pharmacokinetics of melatonin metabolism in this population is warranted. SPONSORSHIP: This project is proudly supported by the Transport Accident Commission.

Treatment Outcomes of Stereotactic Ablative Body Radiotherapy on Extra-cranial Oligometastatic and Oligoprogressive Breast Cancer: Mature Results from a Single Institution Experience.

AIMS: Evidence shows stereotactic ablative body radiotherapy (SABR) is used as a non-invasive ablative therapy in the treatment of multisite oligometastatic (OM) and oligoprogressive (OP) diseases originating from metastatic breast cancer. This study aims to report the treatment outcomes and to investigate what factors that are prognostic in terms of local control, progression-free survival (PFS) and overall survival (OS) in patients receiving SABR for extracranial OM and OP diseases originating from metastatic breast cancer. MATERIALS AND METHODS: A retrospective review on treatment records of patients with OM and OP from metastatic breast cancer who underwent SABR at a single was carried out. SABR was performed with daily image-guided radiotherapy (IGRT) using a dedicated robotic SABR machine. Local control, PFS and OS were calculated using Kaplan-Meier statistics and the post-treatment toxicity data was scored following the CTCAE v4.0 protocol. Univariate and multivariate Cox regression tests were used in the subgroup analysis of prognostic factors on PFS and OS including patients' age, types of follow-up imaging (staging CT only vs whole-body MR/PET), metastases status (OM vs OP), primary breast cancer tumour grade, hormone receptors (ER/PR/HER2) status, change of systemic treatments at SABR, number of metastases, SABR treatment sites and doses. RESULTS: 56 metastatic breast cancer patients (38 patients with OM and 18 patients with OP) were involved in this retrospective review. The median follow-up was 35.6 months (range 4.0-132.9 months). The estimated local control at 1 , 2 and 5 years were 90.9%, 88.7% and 88.7%, respectively. The estimated median PFS was 19.2 months (95%CI 10.3-28.1 months); the PFS at 1, 2 and 5 years were 63.3%, 44.4% and 33.2%. The estimated OS at 1, 2 and 5 years were 98.0%, 91.9% and 74.3%, respectively with the estimated median OS of 105.1 months (95%CI 51.5-158.7 months). The vast majority of patients tolerated the treatment well with the commonest acute side effects as grade 1 fatigue. There were no statistically significant factors found in OS regression analysis. The types of follow-up imaging, metastases status, oestrogen receptor status, and number of metastases for SABR were statistically significant factors (p < 0.05) in the multivariate Cox regression analysis on PFS. CONCLUSION: There are limited studies published on the efficacy and post-treatment toxicities of metastatic breast cancer OM and OP SABR with adequate length of follow-up. This study confirmed that SABR was a safe, non-invasive treatment option for patients with extracranial OM and OP diseases originated from primary breast cancer in terms of the acceptable post-treatment toxicities.

Can shear-wave elastography predict response to neoadjuvant chemotherapy in women with invasive breast cancer?

BACKGROUND: Response of invasive breast cancer to neoadjuvant chemotherapy (NAC) is variable, and prediction of response is imperfect. We aimed to ascertain whether tissue stiffness in breast cancers, as assessed by shear-wave elastography (SWE) before treatment, is associated with response. METHODS: We retrospectively compared pre-treatment tumour mean tissue stiffness, with post-treatment Residual Cancer Burden (RCB) scores and its components in 40 women with breast cancer treated by NAC using Pearson's correlation coefficient (CC), a general linear model and multiple linear regression. Subgroup analysis was carried out for luminal, HER2-positive and basal immuno-histochemical subtypes. RESULTS: Statistically significant correlations were shown between stiffness and RCB scores and between stiffness and percentage tumour cellularity. The correlation between stiffness and percentage cellularity was strongest (CC 0.35 (P<0.0001) compared with CC 0.23 (P=0.004) for the RCB score). The results of a general linear model show that cellularity and RCB score maintain independent relationships with stiffness. By multiple linear regression, only cellularity maintained a significant relationship with stiffness. CONCLUSION: Pre-treatment tumour stiffness measured by SWE, has a statistically significant relationship with pathological response of invasive breast cancer to NAC.

Long-term survival after treatment for Hodgkin's disease (1973-2002): improved survival with successive 10-year cohorts.

BACKGROUND: The Nottinghamshire Lymphoma Registry contains the details of all the patients diagnosed with lymphoma (since 1 January 1973) within a defined geographical area with a population of 1.1 million. It was therefore possible to study the outcome of treatment for Hodgkin's disease for three 10-year cohorts (1973-1982, 1983-1992 and 1993-2002).The aims of the study were to compare survival time among the three patient cohorts, to identify prognostic factors and to estimate relative survival. METHODS: A total of 745 patients diagnosed between 1973 and 2002 were analysed for survival. Survivorship was estimated by the Kaplan-Meier method and parametric survival models. An accelerated failure-time regression was used for multivariate analysis. RESULTS: Overall, patients were observed for 9.8 (0.3-34.82) years (median(range)), on average. One, five and fifteen-year disease-specific survival was found to be 87% (85-90%), 77% (74-80%) and 70% (67-74%), respectively. For those for diagnosed between 1973 and 1982, the 15-year survival was found to be 57%; for 1983-1992, it was 74% and for 1993-2002, it was 83% (P<0.001). The difference remained significant after adjusting for prognostic factors. The actuarial risk of developing a second malignancy at 20 years was for the 1973-1982 cohort, 12.4%, and for the 1983-1992 cohort, 18.8%. CONCLUSION: Treatment advances and effective management of toxicities of treatment over time, have resulted in a significantly longer survival for patients with Hodgkin's disease diagnosed within a defined population.

Parasites, proteomes and systems: has Descartes' clock run out of time?

Systems biology aims to integrate multiple biological data types such as genomics, transcriptomics and proteomics across different levels of structure and scale; it represents an emerging paradigm in the scientific process which challenges the reductionism that has dominated biomedical research for hundreds of years. Systems biology will nevertheless only be successful if the technologies on which it is based are able to deliver the required type and quality of data. In this review we discuss how well positioned is proteomics to deliver the data necessary to support meaningful systems modelling in parasite biology. We summarise the current state of identification proteomics in parasites, but argue that a new generation of quantitative proteomics data is now needed to underpin effective systems modelling. We discuss the challenges faced to acquire more complete knowledge of protein post-translational modifications, protein turnover and protein-protein interactions in parasites. Finally we highlight the central role of proteome-informatics in ensuring that proteomics data is readily accessible to the user-community and can be translated and integrated with other relevant data types.

Combined spinal epidural vs epidural labour analgesia: does initial intrathecal analgesia reduce the subsequent minimum local analgesic concentration of epidural bupivacaine?

Labour analgesia initiated using a combined spinal-epidural (CSE) technique may reduce subsequent epidural bupivacaine requirements compared with an epidural-only technique. We compared the minimum local analgesic concentrations (MLAC) of epidural bupivacaine following initial intrathecal or epidural injection. In a prospective, double-blind study, 115 women requesting epidural analgesia were randomly assigned to receive either an epidural with bupivacaine 20 mg and fentanyl 40 µg or a CSE with intrathecal bupivacaine 2.5 mg and fentanyl 5 µg. Analgesia was assessed using a visual analogue pain score. When further analgesia was requested, bupivacaine 20 ml was given, and the concentration was determined using the technique of up-down sequential allocation. The MLAC of bupivacaine in the epidural group was 0.032% wt/vol (95% CI 0.020-0.044) compared with 0.047% wt/vol (95% CI 0.042-0.052) in the CSE group. Bupivacaine requirements for the second injection were increased following intrathecal analgesia by a factor of 1.45 (p = 0.026) compared with epidural analgesia.

Development and operation of the defence COVID-19 lab as a SARS-CoV-2 diagnostic screening capability for UK military personnel.

BACKGROUND: In the face of the COVID-19 pandemic, the Defence Science and Technology Laboratory (Dstl) and Defence Pathology combined to form the Defence Clinical Lab (DCL), an accredited (ISO/IEC 17025:2017) high-throughput SARS-CoV-2 PCR screening capability for military personnel. LABORATORY STRUCTURE AND RESOURCE: The DCL was modular in organisation, with laboratory modules and supporting functions combining to provide the accredited SARS-CoV-2 (envelope (E)-gene) PCR assay. The DCL was resourced by Dstl scientists and military clinicians and biomedical scientists. LABORATORY RESULTS: Over 12 months of operation, the DCL was open on 289 days and tested over 72 000 samples. Six hundred military SARS-CoV-2-positive results were reported with a median E-gene quantitation cycle (Cq) value of 30.44. The lowest Cq value for a positive result observed was 11.20. Only 64 samples (0.09%) were voided due to assay inhibition after processing started. CONCLUSIONS: Through a sustained effort and despite various operational issues, the collaboration between Dstl scientific expertise and Defence Pathology clinical expertise provided the UK military with an accredited high-throughput SARS-CoV-2 PCR test capability at the height of the COVID-19 pandemic. The DCL helped facilitate military training and operational deployments contributing to the maintenance of UK military capability. In offering a bespoke capability, including features such as testing samples in unit batches and oversight by military consultant microbiologists, the DCL provided additional benefits to the UK Ministry of Defence that were potentially not available from other SARS-CoV-2 PCR laboratories. The links between Dstl and Defence Pathology have also been strengthened, benefitting future research activities and operational responses.