The frequency of interleukin-1ß-producing monocytes is significantly associated with varicella-zoster responses of nursing home residents.

Previous studies have demonstrated that the status of the T cell compartment and inflammation-related factors are associated with the immunogenicity of the varicella-zoster virus (VZV) vaccine in older adults; however, little is known about the roles of other immune cell subsets known to influence the generation and maintenance of immunological memory. Responses to a live-attenuated VZV vaccine were studied in relation to peripheral blood mononuclear cell (PBMC) composition and function in a sample of 30 nursing home residents (aged 80-99 years). Interferon-gamma enzyme-linked immunospot (ELISPOT) was used to measure VZV responses at baseline and 6 weeks following vaccination, and associations were sought with the frequencies of monocytes and T, B and natural killer (NK) cells and the production and secretion of cytokines following their ex-vivo stimulation with different agents. While only the frequency of interleukin (IL)-6+ CD14+ monocytes was inversely associated with post-vaccination VZV response, amounts of IL-1ß, IL-10, IL-17A and tumour necrosis factor (TNF) secreted by PBMCs and the frequency of IL-1ß+ CD14+ monocytes was positively correlated with pre-vaccination VZV response. Furthermore, both bivariate correlation and causal mediation analyses supported the notion that IL-1ß+ CD14+ monocytes were significant mediators of the associations between IL-1ß and TNF secretion by PBMCs and pre-vaccination VZV responses. Our findings implicate a strong cytokine response mediated by inflammatory IL-1ß+ monocytes in coordinating responses of long-lived VZV-reactive memory T cells, but with an opposing effect of IL-6+ CD14+ monocytes. Whether monocyte status promotes or inhibits the induction and/or maintenance of these memory T cells later in life has yet to be determined.

The Impact of Prior Season Vaccination on Subsequent Influenza Vaccine Effectiveness to Prevent Influenza-related Hospitalizations Over 4 Influenza Seasons in Canada.

BACKGROUND: Recent studies have demonstrated the possibility of negative associations between prior influenza vaccines and subsequent influenza vaccine effectiveness (VE), depending on season and strain. We investigated this association over 4 consecutive influenza seasons (2011-2012 through 2014-2015) in Canada. METHODS: Using a matched test-negative design, laboratory-confirmed influenza cases and matched test-negative controls admitted to hospitals were enrolled. Patients were stratified into 4 groups according to influenza vaccine history (not vaccinated current and prior season [referent], vaccinated prior season only, vaccinated current season only, and vaccinated both current and prior season). Conditional logistic regression was used to estimate VE; prior vaccine impact was assessed each season for overall effect and effect stratified by age (<65 years, ≥65 years) and type/subtype (A/H1N1, A/H3N2, influenza B). RESULTS: Overall, mainly nonsignificant associations were observed. Trends of nonsignificant decreased VE among patients repeatedly vaccinated in both prior and current season relative to the current season only were observed in the A/H3N2-dominant seasons of 2012-2013 and 2014-2015. Conversely, in 2011-2012, during which B viruses circulated, and in 2013-2014, when A/H1N1 circulated, being vaccinated in both seasons tended to result in a high VE in the current season against the dominant circulating subtype. CONCLUSIONS: Prior vaccine impact on subsequent VE among Canadian inpatients was mainly nonsignificant. Even in circumstances where we observed a trend of negative impact, being repeatedly vaccinated was still more effective than not receiving the current season's vaccine. These findings favor continuation of annual influenza vaccination recommendations, particularly in older adults. CLINICAL TRIALS REGISTRATION: NCT01517191.

Interim estimates of 2013/14 influenza clinical severity and vaccine effectiveness in the prevention of laboratory-confirmed influenza-related hospitalisation, Canada, February 2014.

During the 2013/14 influenza season in Canada, 631 of 654 hospitalisations for laboratory-confirmed influenza enrolled in sentinel hospitals were due to Influenza A. Of the 375 with known subtype, influenza A(H1N1) accounted for 357. Interim unmatched vaccine effectiveness adjusted for age and presence of one or more medical comorbidities was determined by test-negative case-control design to be 58.5% (90% confidence interval (CI): 43.9-69.3%) overall and 57.9% (90% CI: 37.7-71.5) for confirmed influenza A(H1N1).

Influenza vaccines provide diminished protection but are cost-saving in older adults.

Influenza is associated with substantial morbidity and mortality in adults aged over 65 years. Although vaccination remains the most effective method of preventing influenza and its sequellae, current vaccination strategies provide less protection to older adults than to younger persons. Influenza vaccination in community-dwelling older adults is cost-effective, though there is room for improvement. Newer vaccine strategies considered for use in older adults include alternate routes of administration (intradermal or intranasal), addition of adjuvant, and novel methods of antigen presentation. Measuring cell-mediated immune response to new vaccines in addition to antibody response may correlate better with vaccine efficacy in this population. Whilst pandemic influenza A/H1N1 2009 (pH1N1) has largely spared older adults, the impact of pH1N1 vaccination has yet to be determined.

Aging, frailty and age-related diseases.

The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people.

Validation of the Seegene RV15 multiplex PCR for the detection of influenza A subtypes and influenza B lineages during national influenza surveillance in hospitalized adults.

Background. The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed.Methods. Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses.Results. In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0 % sensitivity, 100 % specificity and 99.7 % accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2 % sensitivity, 100 % specificity and 99.8 % accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages.Conclusions. Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.

Postherpetic neuralgia in the elderly.

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ) or 'shingles' and affects a significant proportion of HZ patients with the disease, with the elderly being most frequently and seriously affected. Characterised by various types of pain (constant, intermittent and stimulus evoked) that persist between 3 months and many years after the resolution of the HZ rash, PHN can have a severe impact on the patient's quality of life and functional ability. PHN remains highly resistant to current treatments. In this review, we discuss the epidemiology, clinical features and management of PHN in the elderly and the potential of vaccination against varicella zoster virus as a means to prevent HZ, and thus decrease the incidence and severity of PHN.

Immunogenicity and reactogenicity of high- vs. standard-dose trivalent inactivated influenza vaccine in healthcare workers: a pilot randomized controlled trial.

OBJECTIVES: To compare immunogenicity, reactogenicity and acceptability of high- and standard-dose trivalent inactivated influenza vaccine (HDTIV, SDTIV) in 18- to 64-year-olds. METHODS: We randomized 18- to 64-year-olds to HDTIV or SDTIV in two consecutive years. We collected serum on days 0 and 21, measured haemagglutination inhibition geometric mean titres (GMT) and compared seroconversion, day 21 titres, seroprotection, reactogenicity and acceptability. RESULTS: Immunogenicity was evaluable in 42 of 47 2014 participants, all 33 both-year participants and 87 of 90 2015-only participants. First-dose HDTIV recipients experienced seroconversion more frequently than SDTIV recipients to A(H3N2) in 2014 (13/21, 62% vs. 4/21, 19%, p 0.01) and to all vaccine strains in 2015: (A(H1N1): 24/42, 57% vs. 15/59, 25%; A(H3N2): 42/42, 100% vs. 47/59, 80%; B: 25/42, 60% vs. 13/59, 22%; all p <0.01). Day 21 haemagglutination inhibition GMT were higher in first and two sequential-year HDTIV vs. SDTIV recipients: A(H1N1): GMT 749 and 768 vs. 384 (p <0.0001, p 0.002); A(H3N2): 1238 and 956 vs. 633 (p 0.0003, p 0.1); and B: 1113 and 1086 vs. 556 (p 0.0005, p 0.02). HDTIV was more reactogenic (local pain score 3 vs. 1 of 10 on day 0/1, p 0.0003), but recipients were equally willing to be revaccinated (HDTIV: 76/83 (92%); SDTIV: 76/80 (95%), p 0.54). The ratios of day 21 GMT in SDTIV recipients vaccinated in 0 to 4 prior years to those in SDTIV and HDTIV recipients vaccinated in 15 or more prior years were A(H1N1): 3.73 and 1.38; A(H3N2) 3.07 and 1.16; and B: 2.01 and 1.21. CONCLUSIONS: HDTIV is more immunogenic and reactogenic and as acceptable as SDTIV in 18- to 64-year-olds.

Changes in CD45 isoform expression after influenza vaccination.

In this study, we report the changes in the isoforms of CD45 expressed on T lymphocytes after influenza vaccination. Young adults were compared to an elderly group (26 participants/group) after vaccination with influenza split-virus vaccine. Peripheral blood mononuclear cells (PBMC) obtained pre-vaccination and 6 and 12 weeks post-vaccination were cultured with live influenza virus. Unstimulated and stimulated (5-day culture with virus) PBMC were labelled with fluorescent monoclonal antibody markers for CD3, CD4, CD8, CD45RA and CD45RO. When compared to the young controls, the elderly group had a higher proportion of CD45RO+RA- and, reciprocally, a lower proportion of CD45RA+RO- cells. In spite of these differences, both groups showed a progressive increase in the proportion of CD45RA+ T lymphocytes (CD4+ and CD8+) following influenza vaccination. In vitro stimulation with influenza virus resulted in a decrease in the proportion of CD45RA+RO- with a concomitant increase in the CD45RA-RO- population, both of which were observed only at 6 weeks post-vaccination. Although the phenotype of classical memory cells for recall antigen is CD45RO+, these results suggest that memory for influenza split-virus vaccine, exists in the CD45RO- population. More importantly, it should be noted that in spite of the decline in CD45RA+ cells with aging, the elderly group showed similar changes in the proportions of all cell phenotypes in response to vaccination, and to subsequent in vitro re-exposure to the virus.

The cell-mediated cytotoxic response to influenza vaccination using an assay for granzyme B activity.

The measurement of cytotoxic T lymphocyte (CTL) activity through 51Cr assays is a very labour intensive method for studying cytotoxicity in human CTL due to the necessary preparation of autologous targets for the assay. An assay for granzyme B, one of a family of serine proteinases implicated in the 'lethal hit' that leads to target cell lysis, is an alternative simple measure of CTL activation. We measured granzyme B activity using its both preferred and unique substrate tert-butyloxycarbonyl-Ala-Ala-Asp-thiobenzyl ester (BAADT) in peripheral blood mononuclear cells (PBMC) obtained from influenza vaccinated subjects, and stimulated with live virus. We found that granzyme B activity increases in parallel and correlates with cytolytic activity as measured by 51Cr release assays in these virus-stimulated PBMC cultures. The assay was then used to measure the cell-mediated cytotoxic response to influenza vaccination in ten healthy elderly subjects. Peak granzyme B activity (day 6) was measured in lysates of PBMC stimulated with influenza virus, obtained from study participants before and after vaccination. We found a significant increase in granzyme B activity from pre-vaccination levels to 4 weeks post vaccination (pre=2.77 U/mg protein, post=7.23 U/mg protein, p=0.002) and a subsequent decline in the activity measured at 12 weeks post vaccination (4.34 U/mg protein, p=0.0007). Due to its substrate specificity which is unique within the family of serine proteases, this assay is highly specific for granzyme B. The assay also avoids the potential hazard of radioactivity (51Cr) in the clinical laboratory and the need for a gamma counter. The assay of granzyme B activity, therefore, provides a simple, specific and responsive method for measuring changes in cell-mediated cytotoxic activity resulting from influenza vaccination.

Mechanisms of basilar skull fracture.

Basilar skull fractures comprise a broad category of injuries that have been attributed to a variety of causal mechanisms. The objective of this work is to develop an understanding of the biomechanical mechanisms that result in basilar skull fractures, specifically focusing on mandibular impact and neck loading as potential mechanisms. In the characterization of the injury mechanisms, three experimental studies have been performed. The first study evaluated the response of the base of the skull to midsymphysis loading on the mental protuberance (chin) of the mandible. Five dynamic impacts using a vertical drop track and one quasi-static test in a servohydraulic test frame have been performed. In each test, clinically relevant mandibular fractures were produced but no basilar skull fractures were observed. The second study assessed the fracture tolerance of the base of the skull subject to direct loading on the temporomandibular joint in conjunction with tensile loading imposed locally around the foramen magnum to simulate the effect of the ligaments and musculature of the neck. Among four specimens that sustained either complete or incomplete basilar skull ring fractures remote from the sites of load application, the mean load at fracture was 4300 +/- 350 N. Energy to fracture was computed in three of those tests and averaged 13.0 +/- 1.7 J. Injuries produced were consistent with clinical observations that have attributed basilar skull ring fractures to mandibular impacts. In the third series of experimental tests, loading responses resulting from cranial vault impacts were investigated using unembalmed human cadaver heads and ligamentous cervical spines. Multiaxis load cells and accelerometers, coupled with high-speed digital video, were used to quantify impact dynamics. The results of these experiments suggest that while there is a greater probability of cervical spine injury, basilar skull ring fractures can result when the head is constrained on the impact surface and the inertia of the torso drives the vertebral column onto the occiput.

Age-related decline in interleukin 2 production in response to influenza vaccine.

Articles in the recent literature document an abnormal antibody response in elderly persons to influenza vaccination. Several studies have presented evidence to show that immune dysfunction in aged mice and humans may be due to a defect in the production of interleukin 2 (IL2) by helper T cells (TH). Cultures of peripheral blood mononuclear cells (PBMC) were prepared from blood samples taken at eight weeks after vaccination (0.5 mL of Armand-Frappier, 15 micrograms/0.5 mL each of A/Taiwan/1/86, A/Leningrad/360/86, and B/Ann Arbor/1/86 administered in the fall of 1987) from a group of elderly men and a young control group. Peripheral blood mononuclear cells were frozen in 10% dimethyl sulfoxide (DMSO) until all the cells were cultured. After stimulation with a 1/320 dilution of the same influenza vaccine, cultures of PBMC from young controls showed a significantly greater increase in IL2 production than the cultures of PBMC from the elderly group of patients. This was statistically significant at both day 3 (P less than .01) and day 5 (P less than .05) of culture using the Mann-Whitney U test. Previous experiments that have shown defective IL2 production related to aging have used potent mitogens such as concanavalin A and phytohemagglutinin to stimulate TH. This study provides evidence that defective IL2 production may also occur in response to physiologic antigenic stimulation and may be one explanation for the reduced efficacy of influenza vaccination in elderly persons.

Mortality and institutionalization following hip fracture.

OBJECTIVES: To identify determinants of mortality and institutionalization after hip fracture and to identify those older hip fracture patients at high risk of death or institutionalization after hip fracture. DESIGN: Population-based prospective inception cohort study of hip fracture patients; patients were assessed in the hospital and at 3 months following the hip fracture. SETTING: Edmonton area hip fracture patients admitted to one of two Edmonton, Alberta, Canada, acute care centers between July 10, 1996, and August 31, 1997. PARTICIPANTS: Patients were residents of the Edmonton area and over the age of 64. Those who had previously fractured the same hip within the past 5 years or had some pathological condition underlying the hip fracture were excluded. Of 610 eligible patients, 558 contributed some baseline information and were included in the mortality analysis; the institutionalization analysis was restricted to the 338 patients who lived in the community before fracture, survived the 3-month period postfracture, and had completed a 3-month follow-up interview. MEASUREMENTS: The baseline interview was done in the hospital to assess mental status, prefracture physical function, prefracture health perception, and prefracture social support. The 3-month follow-up interview was done by phone to assess physical function, health perception, and social support 3 months postfracture. Demographic and comorbidity information was collected from medical records. RESULTS: Low mental status in hospital was found to increase the chances of mortality and institutionalization, and male gender was found to increase mortality risk fourfold. Each additional 10 years of age increased the risk of institutionalization approximately 2.5 times. Patients with lower postfracture physical function had at least five times the risk of institutionalization compared to patients with high postfracture physical function. CONCLUSIONS: Cognitive impairment, older age, and gender were associated with increased risk of poor outcome following hip fracture. The socioeconomic variables--social support and health perception--did not contribute significant additional information in explaining mortality or institutionalization risk. While demographic factors cannot be modified, physical function 3 months postfracture may be amenable to intervention and may reduce the risk of institutionalization. Intervening to increase postfracture physical function may be particularly beneficial to older patients, or to those who are cognitively impaired.

Transmural surgical gown pressure measurements in the operating theater.

Transmural gown pressures encountered when the surgeon comes into contact with a patient were measured in the operating theater. The surgical gown industry has assumed these pressures to be less than 5 psi in testing the efficacy of the gown and drape barrier material to impede bacterial transmission through its pores. In this study, pressure-sensitive contact film and resistive strain gauge recordings made from the surgeon's abdominal region and forearms indicated peak contact pressures in excess of 60 psi. This report indicates a need to reassess the basis of test utilization in evaluating barrier materials used in gowns and drapes.

Standing orders for influenza vaccination increased vaccination rates in inpatient settings compared with community rates.

BACKGROUND: Hospitalization of older adults during the period of influenza vaccination in the fall of each year presents a barrier to immunization against influenza. This study evaluates a program using standing orders for influenza vaccination to increase vaccination rates among hospitalized older adults and to determine the effect of vaccination on readmission rates for influenza-like illness. METHODS: An influenza vaccination program using a standing order policy was implemented to vaccinate all consenting persons 65 years and older prior to hospital discharge. This was a prospective, single center, cohort study in a tertiary care university teaching hospital during an 8-week vaccination period in the fall of 1994 and follow-up during the subsequent influenza season. The vaccination status of each patient was recorded as no vaccination, vaccination received in hospital, or vaccination in the community prior to or after the hospitalization. Hospital vaccination rates were compared with the rate of vaccination of older adults in the community. During the subsequent influenza season, the number of subjects reporting symptoms of influenza-like illness (ILI) or who were readmitted to hospital with influenza-related illness was compared in an analysis of vaccinated versus unvaccinated subjects. RESULTS: Seven hundred and sixty-one patients were interviewed, and 332 of these individuals had been vaccinated in the community prior to their hospital admission. Of the remaining 429 unvaccinated patients who were eligible for vaccination in the study, 171 were vaccinated in our immunization program, eight were vaccinated in the community after discharge, and 244 were not vaccinated. We were able to increase the absolute vaccination rate by 22%, when compared with community rates, with our immunization program. The number of subjects with ILI symptoms or readmission to hospital was too small to compare the vaccinated to the unvaccinated group in the study. CONCLUSIONS: An inpatient influenza immunization program using a standing order policy was able to target a particularly high-risk subset of persons 65 years and over who might otherwise have not received influenza vaccination.

Repository corticotropin injection as an adjunct to smoking cessation during the initial nicotine withdrawal period: results from a family practice clinic.

Fifteen white patients participated in this study of a family-practice-based smoking cessation program in which corticotropin (ACTH) was used to assist patients during the first one to two weeks of abstinence from nicotine. All patients were habitual smokers who had made one or more attempts to quit smoking before entering this program. Treatment consisted of three single intramuscular injections of ACTH. In most cases, declining doses of 160, 80, and 40 U were administered at three-day intervals. The decision to provide additional treatment was based on the response by each volunteer and the investigator's judgment. The mean duration of follow-up was 33 days (range, 17 to 49 days), with the exception of two patients, who have just recently completed therapy. Evidence supporting complete smoking cessation or a significant reduction (80% to greater than 90%) in the number of cigarettes smoked per day was achieved in 13 of the 15 patients. The single nonresponder expressed an initial interest in the program, but showed a lack of motivation thereafter. There was insufficient follow-up on one other patient, who has not been available for monitoring since completion of therapy. Symptoms associated with the tobacco withdrawal syndrome that were reported by the patients included mild irritability and restlessness.

Effects of ankle taping on the motion and loading pattern of the foot for walking subjects.

Gait analysis was used to compare the ground reaction forces, ankle and foot rotations in the sagittal plane, and the center of pressure pattern beneath the right feet of seven normal subjects walking barefoot, with and without their right ankles taped in the neutral position. Instrumentation included a force plate, ankle goniometer, and two accelerometers mounted on top of the foot. The ground reaction forces showed no changes between the same ankle, taped and untaped. Taping served to reduce the range of ankle rotations in the sagittal plane by approximately 20%, with a subsequent increase in the rotation about the metatarsal heads during heel-up. Heel-up occurred earlier in stance when the ankle was taped than with no taping. The vertical force graph was integrated over time when the center of pressure was located beneath the heel and the ball, resulting in two impulse measurements. The heel impulse decreased for each of the 7 subjects and 6 of the 7 subjects displayed an increase in the ball impulse due to taping, indicating that taping served to shift the load-time history away from the heel and toward the ball. The results of this study may apply to fused ankle patients, who may suffer forefoot abnormalities subsequent to ankle fusion surgery.

A system to measure the forces and moments at the knee and hip during level walking.

The forces and moments in the sagittal plane at the knee and hip were calculated using gait data collected during level walking. Accelerations were measured by accelerometers attached to the legs, and the force reactions at the foot were measured by a force plate. The recorded accelerations and the foot forces were used to determine the joint reactions through a Newtonian formulation modeling the leg as articulated, rigid links. Twelve normal subjects were included in this study along with nine lower limb amputees. Obvious differences were observed when comparing amputee data to normal data both at the knee and hip. Gait data obtained by this system can be readily used to form criteria for objective gait analysis and improved prosthesis design.

Experimental impact injury to the cervical spine: relating motion of the head and the mechanism of injury.

The purpose of this study was to analyze, with use of an impact model, the relationships among motion of the head, local deformations of the cervical spine, and the mechanisms of injury; the model consisted of the head and neck of a cadaver. Traditionally, the mechanisms of injury to the cervical spine have been associated with flexion and extension motions of the head and neck. However, the classification of the mechanisms is not always in agreement with the patient's account of the injury or with lacerations and contusions of the scalp, which indicate the site of the impact of the head. Eleven specimens were dropped in an inverted posture with the head and neck in an anatomically neutral position. Forces, moments, and accelerations were recorded, and the impacts were imaged at 1000 frames per second. The velocity at the time of impact was on the order of 3.2 meters per second. The angle and the padding of the impact surface varied. Observable motion of the head did not correspond to the mechanism of the injury to the cervical spine. Injury occurred 2.2 to 18.8 milliseconds after impact and before noticeable motion of the head. However, the classification of the mechanism of the injuries was descriptive of the local deformations of the cervical spine at the time of the injury. Accordingly, it is a useful tool in describing the local mechanism of injury. Buckling of the cervical spine, involving extension between the third and sixth cervical vertebrae and flexion between the seventh and eight cervical vertebrae, was observed. Other, more complex, buckling deformations were also seen, suggesting that the deformations that occur during impact are so complex that they can give rise to a number of different mechanisms of injury.