Forces generated in stabbing attacks: an evaluation of the utility of the mild, moderate and severe scale.

The commonest way of killing in the UK is by a sharp instrument. Knight reported in 1975 that it is impossible to discern with any degree of certainty the degree of force used to create a stab wound. Despite this, expert witnesses continue to approximate the degree of force used for their reports and evidence in court. It is usually subjectively categorized as mild, moderate or severe, based solely on the examination of the wound. We undertook a study considering forces generated in a range of blunt trauma actions, using a novel force plate dynamometer to measure the peak forces obtained by adult male and female volunteers. We then studied forces generated by stabbing skin simulants and porcine samples with knives and screwdrivers. Men generated more force than women during stabbings which was found to be equivalent to somewhere between the blunt trauma actions of pushing a button to a single-handed push. When asked to stab using what they thought was mild, moderate and severe force, although volunteers were able to actively decide the force used, the actual force was found to be influenced by the weapon, sex of the individual, hand used and biological/anatomical site penetrated. This study shows that the forces generated by volunteers in mild, moderate and severe stabbing tests in almost all cases were significantly greater than the forces required for skin penetration. We suggest that the use of subjective force scales is inappropriate. Rather than use of a subjective scale, we suggest that the force required in any stabbing requires investigation in four areas: the tip radius of the weapon, minimal force required for penetration, the sex of the assailant and whether the force required for penetration is greater than that that can be generated by a person stabbing. This allows for the use of an evidence-based two-tier scale to suggest the force required.

The Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and 'hard-to-reach' patients.

BACKGROUND: Participation in low-dose CT (LDCT) lung cancer screening offered in the trial context has been poor, especially among smokers from socioeconomically deprived backgrounds; a group for whom the risk-benefit ratio is improved due to their high risk of lung cancer. Attracting high risk participants is essential to the success and equity of any future screening programme. This study will investigate whether the observed low and biased uptake of screening can be improved using a targeted invitation strategy. METHODS/DESIGN: A randomised controlled trial design will be used to test whether targeted invitation materials are effective at improving engagement with an offer of lung cancer screening for high risk candidates. Two thousand patients aged 60-75 and recorded as a smoker within the last five years by their GP, will be identified from primary care records and individually randomised to receive either intervention invitation materials (which take a targeted, stepped and low burden approach to information provision prior to the appointment) or control invitation materials. The primary outcome is uptake of a nurse-led 'lung health check' hospital appointment, during which patients will be offered a spirometry test, an exhaled carbon monoxide (CO) reading, and an LDCT if eligible. Initial data on demographics (i.e. age, sex, ethnicity, deprivation score) and smoking status will be collected in primary care and analysed to explore differences between attenders and non-attenders with respect to invitation group. Those who attend the lung health check will have further data on smoking collected during their appointment (including pack-year history, nicotine dependence and confidence to quit). Secondary outcomes will include willingness to be screened, uptake of LDCT and measures of informed decision-making to ensure the latter is not compromised by either invitation strategy. DISCUSSION: If effective at improving informed uptake of screening and reducing bias in participation, this invitation strategy could be adopted by local screening pilots or a national programme. TRIAL REGISTRATION: This study was registered with the ISRCTN (International Standard Registered Clinical/soCial sTudy Number: ISRCTN21774741) on the 23rd September 2015 and the NIH ClinicalTrials.gov database (NCT0255810) on the 22nd September 2015.

A prospective cohort study of pulmonary function during pregnancy in women with and without asthma.

BACKGROUND AND OBJECTIVE: Pregnancy alters the severity of asthma unpredictably. Uncertainty still exists about longitudinal changes in pulmonary function during pregnancy in both healthy and asthmatic women. This study aimed to compare pulmonary function changes during pregnancy in healthy and asthmatic women and to determine the relationship between pulmonary function and asthma-related quality of life during pregnancy. A secondary aim was to investigate the application of forced expiratory volume in 6 s (FEV6) for monitoring asthma during pregnancy. METHODS: Pregnant women with (n = 20) and without asthma (n = 20) had pulmonary function tests at 8-20, 21-28 and 29-40 weeks gestation. Those with asthma also completed the Asthma Control Questionnaire (ACQ) and mini Asthma Quality of Life Questionnaire (mAQLQ) at each visit. RESULTS: Pulmonary function declined in both groups at follow-up #1 (more markedly in those with asthma) but then improved at follow-up #2 (more markedly in those with asthma). In those with asthma, ACQ scores increased, while mAQLQ scores declined at follow-up #1; whilst at follow-up #2 these changes were in the opposite direction. FEV6 and forced vital capacity (FVC) were highly correlated (r = 0.88, p < 0.01) in asthmatics. CONCLUSIONS: Pulmonary function changes during second and third trimesters were more pronounced in asthmatics than in healthy women. FEV6 monitoring may assist pregnant women and their health professionals in optimizing asthma management. The changes in pulmonary function in women with asthma were not significantly associated with changes in asthma control or asthma-related quality of life.

Forces required for a knife to penetrate a variety of clothing types.

In stabbing incidents, it is usual for the victim to be clothed and therefore a knife penetrates both clothes and skin. Clothes (other than leather) have been thought to make little difference to the penetration force. However, there is little quantitative data in the literature. In this study, a range of clothes have been tested, either singly or in layers of, for example, T-shirt and shirt, to quantify the additional force required when clothes are present. A materials testing system has been used to test the penetration force required to stab through clothes into a foam-silicone rubber skin simulant. The results show that the force required can be significantly different, particularly when layers of clothing are penetrated. A cotton t-shirt adds c. 8 N to the penetration force, while a T-shirt and jacket can add an additional 21 N. The results allow a more quantitative assessment of forces required in stabbing.

A study considering the force required for broken glass bottles to penetrate a skin simulant.

Injuries and assaults related to alcohol consumption are a growing concern in many countries. In such cases, the use of impulsive weapons, an object from the immediate environment, such as a glass bottle, is not uncommon. This current study utilises a material testing system to measure the force required to push a broken glass bottle into a skin simulant with the displacement of the bottle into the skin simulant being recorded simultaneously, using a linear variable differential transformer (LVDT). From this data, load versus displacement plots were produced. Multi-detector computed tomography (MDCT) was also used to analyse bottle wall thickness to determine if a relationship could be found between force required for penetration and bottle wall thickness. The forces required for the penetration of the skin simulant ranged from 9.8 to 56.7 N. The range was found to be independent of bottle type with the variation in force for penetration being attributed to the varying fracture points, with some fractures presenting a sharper point on first contact with the skin. Although the dangers associated with the use of broken bottles as weapons is apparent, there is a paucity of information in this area in the current English literature, which this study has addressed. The results of this study also highlight the risks of attempting reconstructions of broken bottle stab events.

The Global Lung Initiative 2012 reference values reflect contemporary Australasian spirometry.

We aimed to ascertain the fit of the European Respiratory Society Global Lung Initiative 2012 reference ranges to contemporary Australasian spirometric data. Z-scores for spirometry from Caucasian subjects aged 4-80 years were calculated. The mean (SD) Z-scores were 0.23 (1.00) for forced expirtory volume in 1 s (FEV(1)), 0.23 (1.00) for forced vital capacity (FVC), -0.03 (0.87) for FEV(1)/FVC and 0.07 (0.95) for forced expiratory flows between 25% and 75% of FVC. These results support the use of the Global Lung Initiative 2012 reference ranges to interpret spirometry in Caucasian Australasians.

The all-age spirometry reference ranges reflect contemporary Australasian spirometry.

BACKGROUND AND OBJECTIVE: Advances in statistical modelling have allowed the creation of smoothly changing spirometry reference ranges that apply across a wide age range and better define the lower limit of normal. The objective of this study was to assess the agreement of the Stanojevic 2009 all-age reference ranges to contemporary lung function data to verify the appropriateness of this reference for clinical use in Australia and New Zealand. METHODS: Spirometry data from healthy Caucasians measured between 2000-2009 in Australia and New Zealand were collected. Z-scores were calculated for the standard spirometry outcomes based on the all-age reference ranges. RESULTS: Spirometry from 2066 subjects aged 4-80 years (55% male) from 14 centres were eligible. Statistically, the collated contemporary dataset differed from the all-age reference ranges, but these differences were relatively small and clinically irrelevant representing differences of approximately 3% predicted. Significant differences were also observed between some centres and equipment, potentially indicating varying influence of equipment or subject selection. CONCLUSIONS: Spirometry from contemporary Australasian healthy subjects fits the all-age reference ranges well. While the current study supports the use of the all-age reference ranges, the between-centre differences highlight the need for spirometry to be used in conjunction with other clinical findings.

Lung volume and ventilation inhomogeneity in preterm infants at 15-18 months corrected age.

OBJECTIVE: To assess whether lung volume and ventilation inhomogeneity in preterm infants at 15-18 months corrected age, and the change in these outcomes from the newborn period to 15-18 months corrected age, depend on gestational age (GA) at birth and the severity of neonatal lung disease. STUDY DESIGN: Preterm (GA range, 23-32 weeks) and term healthy control infants were studied in quiet sedated sleep at 15-18 months corrected age by multiple breath washout with 5% sulfur hexafluoride using an ultrasonic flowmeter. Valid measurements were obtained from 58 infants. Multivariate and multilevel regression was used to analyze outcomes. RESULTS: Functional residual capacity (FRC), lung clearance index, and first and second to zeroeth moment ratios were calculated. After accounting for body size at test, FRC at follow-up, and the increase in FRC from the newborn period to 15-18 months corrected age were positively associated with GA and negatively associated with the duration of endotracheal ventilation. Indices of ventilation inhomogeneity were unaltered by GA and the duration of endotracheal ventilation. CONCLUSIONS: In very preterm infants, GA and the duration of endotracheal ventilation are independently associated with reduced lung volume and lung growth during infancy, although the effect size of these findings is small.

Lung function in infants with cystic fibrosis diagnosed by newborn screening.

RATIONALE: Progressive lung damage in cystic fibrosis (CF) starts in infancy, and early detection may aid preventative strategies. OBJECTIVES: To measure lung function in infants with CF diagnosed by newborn screening and describe its association with pulmonary infection and inflammation. METHODS: Infants with CF (n = 68, 6 weeks to 30 months of age) and healthy infants without CF (n = 49) were studied. Forced vital capacity, FEV(0.5), and forced expiratory flows at 75% of exhaled vital capacity (FEF(75)) were measured using the raised-volume rapid thoracoabdominal compression technique. Forty-eight hours later, infants with CF had bronchoalveolar lavage (BAL) for assessment of pulmonary infection and inflammation. MEASUREMENTS AND MAIN RESULTS: In the CF group, the deficit in FEV(0.5) z score increased by -0.77 (95% confidence interval, -1.14 to -0.41; P < 0.001) with each year of age. The mean FEV(0.5) z score did not differ between infants with CF and healthy control subjects less than 6 months of age (-0.06 and 0.02, respectively; P = 0.87). However, the mean FEV(0.5) z score was lower by 1.15 in infants with CF who were older than 6 months of age compared with healthy infants (P < 0.001). FVC and FEF(75) followed a similar pattern. Pulmonary infection and inflammation in BAL samples did not explain the lung function results. CONCLUSIONS: Lung function, measured by forced expiration, is normal in infants with CF at the time of diagnosis by newborn screening but is diminished in older infants. These findings suggest that in CF the optimal timing of therapeutic interventions aimed at preserving lung function may be within the first 6 months of life.

Early detection of lung disease in children with cystic fibrosis using lung function.

Measurement of lung function is routine in older children and adults with cystic fibrosis (CF) but not in infants and preschool children. Pulmonary infection, neutrophil-dominated inflammation and clinical exacerbations in young children similar to those seen in older subjects have been identified and highlight the urgent need to evaluate lung function in early life. Mounting evidence suggests lung function techniques sensitive to changes in peripheral lung function may be required to detect the early functional abnormalities in infants and preschool children with CF. In addition, the majority of studies in young children with CF have not reported longitudinal data and therefore the prognostic potential of existing lung function methods to track disease progression is poorly understood. This review aims to describe recent research findings in infants and preschool children and to outline currently available lung function techniques, issues around their standardization and their relative advantages and disadvantages in young children with CF.

Lateral versus anterior thoracic thrusts in the generation of airway pressure in anaesthetised pigs.

OBJECTIVE: Anterior chest thrusts (with the subject sitting or standing and thrusts applied to the lower sternum) are recommended by the Australian Resuscitation Council as part of the sequence for clearing upper airway obstruction by a foreign body. Lateral chest thrusts (with the victim lying on their side) are no longer recommended due to a lack of evidence. We compared anterior, lateral chest and abdominal thrusts in the generation of airway pressures using a suitable animal model. METHODS: This was a repeated-measures, cross-over, clinical trial of eight anaesthetised, intubated, adult pigs. For each animal, ten trials of each technique were undertaken with the upper airway obstructed. A chest/abdominal pressure transducer, a pneumotachograph and an intra-oesophageal balloon catheter recorded chest/abdominal thrust, expiratory air flows, airway and intrapleural pressures, respectively. RESULTS: The mean (SD) thrust pressures generated for the anterior, lateral and abdominal techniques were 120.9 (11.0), 135.2 (20.0), and 142.4 (27.3)cmH(2)O, respectively (p<0.0001). The mean (SD) peak expiratory airway pressures were 6.5 (3.0), 18.0 (5.5) and 13.8 (6.7)cmH2O, respectively (p<0.0001). The mean (SD) peak expiratory intrapleural pressures were 5.4 (2.7), 13.5 (6.2) and 10.3 (8.5)cmH(2)O, respectively (p<0.0001). At autopsy, no rib, intra-abdominal or intra-thoracic injury was observed. CONCLUSION: Lateral chest and abdominal thrust techniques generated significantly greater airway and pleural pressures than the anterior thrust technique. We recommend further research to provide additional evidence that may inform management guidelines for clearing foreign body upper airway obstruction.

Air trapping on chest CT is associated with worse ventilation distribution in infants with cystic fibrosis diagnosed following newborn screening.

BACKGROUND: In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF. METHODS: Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M(1)/M(0) and M(2)/M(0), respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping. RESULTS: Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M(2)/M(0) but not LCI or M(1)/M(0). There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes. CONCLUSION: These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF.

Interaction of HLA-DR with an acidic face of HLA-DM disrupts sequence-dependent interactions with peptides.

HLA-DM (DM) edits major histocompatibility complex class II (MHCII)-bound peptides in endocytic compartments and stabilizes empty MHCII molecules. Crystal structures of DM have revealed similarity to MHCII but not how DM and MHCII interact. We used mutagenesis to map a MHCII-interacting surface on DM. Mutations on this surface impair DM action on HLA-DR and -DP in cells and DM-dependent peptide loading in vitro. The orientation of DM and MHCII predicted by these studies guided design of soluble DM and DR molecules fused to leucine zippers via their beta chains, resulting in stable DM/DR complexes. Peptide release from the complexes was fast and only weakly sequence dependent, arguing that DM diminishes the selectivity of the MHCII groove. Analysis of soluble DM action on soluble DR/peptide complexes corroborates this conclusion.