Validity of submaximal aerobic capacity and strength tests in firefighters.

BACKGROUND: Typically, the fitness of UK firefighters is assessed via submaximal estimate methods due to the low demands on time, money, expertise and equipment. However, the firefighter-specific validity of such testing in relation to maximum aerobic capacity (V˙O2max) and particularly muscular strength is not well established. AIMS: To examine the validity of submaximal methods to estimate V˙O2max and maximal strength in operational firefighters. METHODS: Twenty-two full-time operational firefighters (3 female) completed same-day submaximal (Chester Step Test; CST) and maximal (treadmill) assessments of V˙O2max, with a sub-sample of 10 firefighters (1 female) also completing submaximal and maximal back-squat (i.e. one repetition maximum; 1RM) assessments. All participants then completed the Firefighter Simulation Test (FFST) within 2-4 days. RESULTS: CST underestimated actual V˙O2max by 1.4 ml·kg-1·min-1 (~3%), although V˙O2max values were positively correlated (r = 0.61, P < 0.01) and not significantly different. Estimated V˙O2max values negatively correlated with FFST performance (r = -0.42). Predicted 1RM underestimated actual 1RM by ~2%, although these values were significantly correlated (r = 0.99, P < 0.001) and did not significantly differ. The strongest predictive model of FFST performance included age, body mass index, and direct maximal measures of 1RM and V˙O2max. CONCLUSIONS: Submaximal back-squat testing offers good validity in estimating maximum firefighter strength without exposure to the fatigue associated with maximal methods. The CST provides a reasonably valid and cost-effective V˙O2max estimate which translates to firefighting task performance, although the error observed means it should be used cautiously when making operational decisions related to V˙O2max benchmarks.

A practical guide to mathematical methods for estimating infectious disease outbreak risks.

Mathematical models are increasingly used throughout infectious disease outbreaks to guide control measures. In this review article, we focus on the initial stages of an outbreak, when a pathogen has just been observed in a new location (e.g., a town, region or country). We provide a beginner's guide to two methods for estimating the risk that introduced cases lead to sustained local transmission (i.e., the probability of a major outbreak), as opposed to the outbreak fading out with only a small number of cases. We discuss how these simple methods can be extended for epidemiological models with any level of complexity, facilitating their wider use, and describe how estimates of the probability of a major outbreak can be used to guide pathogen surveillance and control strategies. We also give an overview of previous applications of these approaches. This guide is intended to help quantitative researchers develop their own epidemiological models and use them to estimate the risks associated with pathogens arriving in new host populations. The development of these models is crucial for future outbreak preparedness. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

A direct comparison of methods for assessing the threat from emerging infectious diseases in seasonally varying environments.

Seasonal variations in environmental conditions lead to changing infectious disease epidemic risks at different times of year. The probability that early cases initiate a major epidemic depends on the season in which the pathogen enters the population. The instantaneous epidemic risk (IER) can be tracked. This quantity is straightforward to calculate, and corresponds to the probability of a major epidemic starting from a single case introduced at time t=t0, assuming that environmental conditions remain identical from that time onwards (i.e. for all t≥t0). However, the threat when a pathogen enters the population in fact depends on changes in environmental conditions occurring within the timescale of the initial phase of the outbreak. For that reason, we compare the IER with a different metric: the case epidemic risk (CER). The CER corresponds to the probability of a major epidemic starting from a single case entering the population at time t=t0, accounting for changes in environmental conditions after that time. We show how the IER and CER can be calculated using different epidemiological models (the stochastic Susceptible-Infectious-Removed model and a stochastic host-vector model that is parameterised using temperature data for Miami) in which transmission parameter values vary temporally. While the IER is always easy to calculate numerically, the adaptable method we provide for calculating the CER for the host-vector model can also be applied easily and solved using widely available software tools. In line with previous research, we demonstrate that, if a pathogen is likely to either invade the population or fade out on a fast timescale compared to changes in environmental conditions, the IER closely matches the CER. However, if this is not the case, the IER and the CER can be significantly different, and so the CER should be used. This demonstrates the need to consider future changes in environmental conditions carefully when assessing the risk posed by emerging pathogens.

New IR imaging modalities for cancer detection and for intra-cell chemical mapping with a sub-diffraction mid-IR s-SNOM.

We present two new modalities for generating chemical maps. Both are mid-IR based and aimed at the biomedical community, but they differ substantially in their technological readiness. The first, so-called "Digistain", is a technologically mature "locked down" way of acquiring diffraction-limited chemical images of human cancer biopsy tissue. Although it is less flexible than conventional methods of acquiring IR images, this is an intentional, and key, design feature. It allows it to be used, on a routine basis, by clinical personnel themselves. It is in the process of a full clinical evaluation and the philosophy behind the approach is discussed. The second modality is a very new, probe-based "s-SNOM", which we are developing in conjunction with a new family of tunable "Quantum Cascade Laser" (QCL) diode lasers. Although in its infancy, this instrument can already deliver ultra-detailed chemical images whose spatial resolutions beat the normal diffraction limit by a factor of ∼1000. This is easily enough to generate chemical maps of the insides of single cells for the first time, and a range of new possible scientific applications are explored.

A simulation-based approach for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data.

Tracking pathogen transmissibility during infectious disease outbreaks is essential for assessing the effectiveness of public health measures and planning future control strategies. A key measure of transmissibility is the time-dependent reproduction number, which has been estimated in real-time during outbreaks of a range of pathogens from disease incidence time series data. While commonly used approaches for estimating the time-dependent reproduction number can be reliable when disease incidence is recorded frequently, such incidence data are often aggregated temporally (for example, numbers of cases may be reported weekly rather than daily). As we show, commonly used methods for estimating transmissibility can be unreliable when the timescale of transmission is shorter than the timescale of data recording. To address this, here we develop a simulation-based approach involving Approximate Bayesian Computation for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data. We first use a simulated dataset representative of a situation in which daily disease incidence data are unavailable and only weekly summary values are reported, demonstrating that our method provides accurate estimates of the time-dependent reproduction number under such circumstances. We then apply our method to two outbreak datasets consisting of weekly influenza case numbers in 2019-20 and 2022-23 in Wales (in the United Kingdom). Our simple-to-use approach will allow accurate estimates of time-dependent reproduction numbers to be obtained from temporally aggregated data during future infectious disease outbreaks.

Using real-time modelling to inform the 2017 Ebola outbreak response in DR Congo.

Important policy questions during infections disease outbreaks include: i) How effective are particular interventions?; ii) When can resource-intensive interventions be removed? We used mathematical modelling to address these questions during the 2017 Ebola outbreak in Likati Health Zone, Democratic Republic of the Congo (DRC). Eight cases occurred before 15 May 2017, when the Ebola Response Team (ERT; co-ordinated by the World Health Organisation and DRC Ministry of Health) was deployed to reduce transmission. We used a branching process model to estimate that, pre-ERT arrival, the reproduction number was R = 1.49 (95% credible interval ( 0.67, 2.81 ) ). The risk of further cases occurring without the ERT was estimated to be 0.97 (97%). However, no cases materialised, suggesting that the ERT's measures were effective. We also estimated the risk of withdrawing the ERT in real-time. By the actual ERT withdrawal date (2 July 2017), the risk of future cases without the ERT was only 0.01, indicating that the ERT withdrawal decision was safe. We evaluated the sensitivity of our results to the estimated R value and considered different criteria for determining the ERT withdrawal date. This research provides an extensible modelling framework that can be used to guide decisions about when to relax interventions during future outbreaks.

Exact calculation of end-of-outbreak probabilities using contact tracing data.

A key challenge for public health policymakers is determining when an infectious disease outbreak has finished. Following a period without cases, an estimate of the probability that no further cases will occur in future (the end-of-outbreak probability) can be used to inform whether or not to declare an outbreak over. An existing quantitative approach (the Nishiura method), based on a branching process transmission model, allows the end-of-outbreak probability to be approximated from disease incidence time series, the offspring distribution and the serial interval distribution. Here, we show how the end-of-outbreak probability under the same transmission model can be calculated exactly if data describing who-infected-whom (the transmission tree) are also available (e.g. from contact tracing studies). In that scenario, our novel approach (the traced transmission method) is straightforward to use. We demonstrate this by applying the method to data from previous outbreaks of Ebola virus disease and Nipah virus infection. For both outbreaks, the traced transmission method would have determined that the outbreak was over earlier than the Nishiura method. This highlights that collection of contact tracing data and application of the traced transmission method may allow stringent control interventions to be relaxed quickly at the end of an outbreak, with only a limited risk of outbreak resurgence.

A theoretical framework for transitioning from patient-level to population-scale epidemiological dynamics: influenza A as a case study.

Multi-scale epidemic forecasting models have been used to inform population-scale predictions with within-host models and/or infection data collected in longitudinal cohort studies. However, most multi-scale models are complex and require significant modelling expertise to run. We formulate an alternative multi-scale modelling framework using a compartmental model with multiple infected stages. In the large-compartment limit, our easy-to-use framework generates identical results compared to previous more complicated approaches. We apply our framework to the case study of influenza A in humans. By using a viral dynamics model to generate synthetic patient-level data, we explore the effects of limited and inaccurate patient data on the accuracy of population-scale forecasts. If infection data are collected daily, we find that a cohort of at least 40 patients is required for a mean population-scale forecasting error below 10%. Forecasting errors may be reduced by including more patients in future cohort studies or by increasing the frequency of observations for each patient. Our work, therefore, provides not only an accessible epidemiological modelling framework but also an insight into the data required for accurate forecasting using multi-scale models.

Initial Analysis of OSTA-1 Ocean Color Experiment Imagery.

Ocean images were obtained at three widely separated locations on the earth as part of NASA's ocean color experiment. Digital computer enhancement and band-ratioing techniques were applied to radiometrically corrected spectral data to emphasize patterns of chlorophyll distribution and, in one case, of bottom topography. The chlorophyll pattern in the Yellow Sea between China and Korea was evident in a scene produced from shuttle orbit 24. The effects of the discharge from the Yangtze and other rivers were also observed. Two scenes from orbits 30 and 32 revealed the movement of patches of plankton in the Gulf of Cádiz. Geometric corrections of these images permitted ocean current velocities in the vicinity to be deduced. The variability in water depth over the Grand Bahama Bank was estimated by using the blue-green channel of the instrument. The very clear water conditions in the area caused bottom-reflected sunlight to produce a sensor signal that was inversely related to the depth of the water.

Environment and behavior of 2.5-million-year-old Bouri hominids.

The Hata Member of the Bouri Formation is defined for Pliocene sedimentary outcrops in the Middle Awash Valley, Ethiopia. The Hata Member is dated to 2.5 million years ago and has produced a new species of Australopithecus and hominid postcranial remains not currently assigned to species. Spatially associated zooarchaeological remains show that hominids acquired meat and marrow by 2.5 million years ago and that they are the near contemporary of Oldowan artifacts at nearby Gona. The combined evidence suggests that behavioral changes associated with lithic technology and enhanced carnivory may have been coincident with the emergence of the Homo clade from Australopithecus afarensis in eastern Africa.

African Homo erectus: old radiometric ages and young Oldowan assemblages in the Middle Awash Valley, Ethiopia.

Fossils and artifacts recovered from the middle Awash Valley of Ethiopia's Afar depression sample the Middle Pleistocene transition from Homo erectus to Homo sapiens. Ar/Ar ages, biostratigraphy, and tephrachronology from this area indicate that the Pleistocene Bodo hominid cranium and newer specimens are approximately 0.6 million years old. Only Oldowan chopper and flake assemblages are present in the lower stratigraphic units, but Acheulean bifacial artifacts are consistently prevalent and widespread in directly overlying deposits. This technological transition is related to a shift in sedimentary regime, supporting the hypothesis that Middle Pleistocene Oldowan assemblages represent a behavioral facies of the Acheulean industrial complex.

Accurate forecasts of the effectiveness of interventions against Ebola may require models that account for variations in symptoms during infection.

Epidemiological models are routinely used to predict the effects of interventions aimed at reducing the impacts of Ebola epidemics. Most models of interventions targeting symptomatic hosts, such as isolation or treatment, assume that all symptomatic hosts are equally likely to be detected. In other words, following an incubation period, the level of symptoms displayed by an individual host is assumed to remain constant throughout an infection. In reality, however, symptoms vary between different stages of infection. During an Ebola infection, individuals progress from initial non-specific symptoms through to more severe phases of infection. Here we compare predictions of a model in which a constant symptoms level is assumed to those generated by a more epidemiologically realistic model that accounts for varying symptoms during infection. Both models can reproduce observed epidemic data, as we show by fitting the models to data from the ongoing epidemic in the Democratic Republic of the Congo and the 2014-16 epidemic in Liberia. However, for both of these epidemics, when interventions are altered identically in the models with and without levels of symptoms that depend on the time since first infection, predictions from the models differ. Our work highlights the need to consider whether or not varying symptoms should be accounted for in models used by decision makers to assess the likely efficacy of Ebola interventions.

The effect of polyethylene thickness in fixed- and mobile-bearing total knee replacements.

In this paper fixed- and mobile-bearing implants were simulated using a multibody dynamic model and a finite element model to investigate the contact pressure distribution in the ultra high molecular weight polyethylene tibial bearing component. The thickness of polyethylene varied from 6.8 to 12.3 mm and the polyethylene was modelled as a non-linear material. It was found that the contact pressure on the polyethylene decreased in the fixed-bearing implant when the thickness of polyethylene increased from 6.8 to 8 and 9.6 mm, but there was little further decrease in pressure with the increase of polyethylene thickness from 9.6 to 11.0 and 12.3 mm. In the mobile-bearing implant, no increase in contact pressure on the superior surface was found with the increase in the thickness of the polyethylene; however, the contact pressures on the inferior contact surface of the thicker designs were higher than those in the 6.8 mm design. The numerical results obtained in this paper are in good agreement with published experimental test results. Moreover, the paper presents a detailed pressure distribution on the tibial bearing component during a full gait cycle.

[Clinical reasoning and decision-making in practice. A man with swelling of both corners of the jaw]. / Klinisch denken en beslissen in de praktijk. Een man met een zwelling van beide kaakhoeken.

A 33-year-old man was referred to an oral surgeon by his general practitioner because ofa bilateral swelling in both jaws. A CT-scan of the head showed enlargement of the parotid glands. After exclusion of mumps and sialolithiasis the patient was treated with oral antibiotics. The swelling failed to improve and the patient was sent to an internist. A repeated medical history revealed that he also had symptoms of sicca syndrome. Sjögren's syndrome was excluded only after negative immunoserological tests and sublabial salivary gland biopsy. A chest X-ray showed enlarged bilateral hilar lymph nodes, confirming the diagnosis of sarcoidosis. A gallium scintigraphy provided further support for this diagnosis. No treatment was initiated and the patient recovered slowly afterwards.

[Clinical reasoning and decision-making in practice. A patient with fever and pancytopenia]. / Klinisch denken en beslissen in de praktijk. Een patiënt met koorts en pancytopenie.

An 82-year-old man was admitted with a 1-week history of chilling fever and dry cough. Laboratory tests revealed pancytopenia and elevated levels of C-reactive protein and lactic dehydrogenase (LDH). Screening for infectious diseases was negative. A bone marrow biopsy showed aspecific findings. The combination of pancytopenia, persistent fever, elevated LDH and hepatomegaly (demonstrated by ultrasound examination of the abdomen) was suggestive of the haemophagocytic syndrome. This was confirmed by very high levels of ferritin and soluble interleukin-2 receptor in the blood. In addition, re-examination of the bone marrow showed several haemophagocytic histiocytes. A polymerase chain reaction for Epstein-Barr virus (EBV) revealed a very high viral load. Since the patient had a history of an increased level of anti-EBV immunoglobulin-G, this was explained by a reactivation of the EBV infection. On the sixth day in hospital the patient developed signs of bilateral pneumonia and subsequent multiple organ failure. Despite intensive treatment the patient died. Autopsy revealed no haematological or other malignancies, but did show haemophagocytosis in many organs. It was then concluded that the patient had a virus-associated haemophagocytic syndrome, due to a reactivation of EBV, for which no underlying cause was found.

[Severe anaemia caused by Human Parvovirus B19 infection in a patient with autoimmune haemolytic anaemia and a B-cell non-Hodgkin lymphoma]. / Ernstige anemie door infectie met het Humaan parvovirus B19 bij een patiënt met een auto-immuun-hemolytische anemie en een B-cel-non-hodgkinlymfoom.

A 65-year-old man with a 15-year history of 'leukemicised' low-grade lymphocytic B-cell non-Hodgkin lymphoma with a low-titre of IgM kappa paraprotein was admitted with severe anaemia and reticulocytopenia. Treatment with prednisone and chlorambucil had been started two weeks earlier because of a recently diagnosed Coombs-positive haemolytic anaemia. He also received a blood transfusion at that time. During his stay in the hospital, a crista biopsy was performed that revealed no signs of bone marrow suppression but markedly enlarged pro-erythroblasts. Although a serologic test for Human Parvovirus-B19 was negative, PCR showed a sharply increased viral load with more than 1 x 10(11) copies/ml, compatible with a primary parvovirus infection. In retrospect, an earlier transfusion of blood that had not been screened for parvovirus was probably the culprit. Treatment with human immunoglobulin was effective in lowering the viral load and normalising the haemoglobin. This case illustrates that reticulocytopenia in a patient with a haematologic disorder accompanied by a shortened erythrocyte life-span is suggestive for a primary parvovirus infection, especially following a recent transfusion. To prevent transmission of Human Parvovirus B19 via blood transfusion, the Health Council of the Netherlands published a guideline indicating that patients at high risk for a complicated infection with Human Parvovirus B19 should be given 'virus-free' blood products.

[Clinical reasoning and decision-making in practice. A man with hip pain and fever]. / Klinisch denken en beslissen in de praktijk. Een man met pijn in de heup en koorts.

A 42-year-old man was admitted to the hospital because of pain in the left hip. On examination he was febrile at 38 degrees C and he walked with a limp. The chest, abdomen and extremities were normal. Laboratory tests showed an elevated ESR and CRP. The ANA test was positive. CT-scan of the abdomen revealed a mass in the psoas region and some dilatation of the left renal pelvis. Following the histological results of the first and second diagnostic percutaneous biopsies, the clinicians suspected idiopathic retroperitoneal fibrosis. They treated the patient with corticosteroids for a period of 4 weeks. After a short interval of improvement this treatment failed and a third biopsy was taken. Subsequently, the diagnosis of anaplastic large cell lymphoma (ALCL) was made. The patient was successfully treated with combination chemotherapy. Usually, in practice, clinical reasoning and decision-making is carried out in accordance with Bayes' theorem. But when the a priori probability of disease is unknown and the likelihood ratio of a diagnostic test unavailable, one has to combine the available 'evidence' with critical thinking, interdisciplinary communication, judgement, intuition and common sense.

The societal costs of intracerebral hemorrhage in Spain.

This study estimates the lifetime societal costs associated with incident intracerebral hemorrhage (ICH) in Spain. An epidemiological model of ICH incidence, survival and morbidity was developed using retrospective data from 28 hospitals in Andalusia and published data identified in a systematic literature review. Data on resource utilization and costs were obtained from five hospitals in the Canary Islands, whereas cost of outpatient care, informal care and lost productivity were obtained from standardized questionnaires completed by survivors of ICH. The lifetime societal costs of incident ICH in Spain is estimated at 46,193 euros per patient. Direct medical costs accounted for 32.7% of lifetime costs, whilst 67.3% were related to indirect costs. One-third of direct medical costs over the first year were attributable to follow-up care, including rehabilitation. Indirect costs were dominated by costs of informal care (71.2%). The aggregated lifetime societal costs for the estimated 12,534 Spanish patients with a first-ever ICH in 2004 was 579 million euros. ICH implies substantial costs to society primarily due to formal and informal follow-up care and support needed after hospital discharge. Interventions that offer survival benefits without improving patients' functional status are likely to further increase the societal costs of ICH.

A dynamic model of simulating stress distribution in the distal femur after total knee replacement.

The aim of this study has been to develop a dynamic model of the knee joint after total knee replacement (TKR) to analyse the stress distribution in the distal femur during daily activities. Using MSC/ADAMS and MSC/MARC software, a dynamic model of an implanted knee joint has been developed. This model consists of the components of the knee prosthesis as well as the bones and ligaments of the knee. The femur, tibia, fibula, and patella have been modelled as mixed cortico-cancellous bone. The distal part of femur has been modelled as a flexible body with springs used to simulate the ligaments positioned at their anatomical insertion points. With this dynamic model a gait cycle was simulated. Stress shielding was identified in the distal femur after TKR, which is consistent with other investigators' results. Interestingly, higher stresses were found in the bone adjacent to the femoral component peg. This dynamic model can now be used to analyse the stress distribution in the distal femur with different load conditions. This will help to improve implant designs and will allow comparison of prostheses from different manufacturers.