Dissipative Reactions with Intermediate-Energy Beams: A Novel Approach to Populate Complex-Structure States in Rare Isotopes.

A novel pathway for the formation of multiparticle-multihole excited states in rare isotopes is reported from highly energy- and momentum-dissipative inelastic-scattering events measured in reactions of an intermediate-energy beam of ^{38}Ca on a Be target. The negative-parity, complex-structure final states in ^{38}Ca are observed following the in-beam γ-ray spectroscopy of events in the ^{9}Be(^{38}Ca,^{38}Ca+γ)X reaction in which the scattered projectile loses longitudinal momentum of order Δp_{||}=700 MeV/c. The characteristics of the observed final states are discussed and found to be consistent with the formation of excited states involving the rearrangement of multiple nucleons in a single, highly energetic projectile-target collision. Unlike the far-less-dissipative, surface-grazing reactions usually exploited for the in-beam γ-ray spectroscopy of rare isotopes, these more energetic collisions appear to offer a practical pathway to nuclear-structure studies of more complex multiparticle configurations in rare isotopes-final states conventionally thought to be out of reach with high-luminosity fast-beam-induced reactions.

New

The discrepancy between observations from γ-ray astronomy of the ^{60}Fe/^{26}Al γ-ray flux ratio and recent calculations is an unresolved puzzle in nuclear astrophysics. The stellar ß-decay rate of ^{59}Fe is one of the major nuclear uncertainties impeding us from a precise prediction. The important Gamow-Teller strengths from the low-lying states in ^{59}Fe to the ^{59}Co ground state are measured for the first time using the exclusive measurement of the ^{59}Co(t,^{3}He+γ)^{59}Fe charge-exchange reaction. The new stellar decay rate of ^{59}Fe is a factor of 3.5±1.1 larger than the currently adopted rate at T=1.2 GK. Stellar evolution calculations show that the ^{60}Fe production yield of an 18 solar mass star is decreased significantly by 40% when using the new rate. Our result eliminates one of the major nuclear uncertainties in the predicted yield of ^{60}Fe and alleviates the existing discrepancy of the ^{60}Fe/^{26}Al ratio.

Incidence and associated risk factors for falls in adults with intellectual disability.

BACKGROUND: People with intellectual disability (ID) experience age-related changes earlier in life, and as such, falls among people with ID are of serious concern. Falls can cause injury and consequently reduce quality of life. Limited studies have investigated the incidence of falls among people with ID and the associated risk factors. The purpose of this study was to investigate the incidence of falls and risk factors for falling in people with ID living in the community. METHODS: A prospective observational cohort (n = 78) of community-dwelling adults with ID. Characteristics measured at baseline included falls history, medication use, balance and mobility. Falls were reported for 6 months using monthly calendars and phone calls. Data were analysed using univariate and multivariate logistic regression to identify risk factors associated with falling. RESULTS: Participants [median (interquartile range) age 49 (43-60) years, female n = 32 (41%)] experienced 296 falls, with 36 (46.2%) participants having one or more falls. The incidence of falls was 5.7 falls (injurious falls = 0.8) per person year (one outlier removed from analysis). A history of falls [adjusted odds ratio (OR): 6.37, 95% confidence interval (CI) (1.90-21.34)] and being ambulant [adjusted OR: 4.50, 95% CI (1.15-17.67)] were associated with a significantly increased risk of falling. Falls were significantly less frequent among participants taking more than four medications [adjusted OR: 0.22, 95% CI (0.06-0.83)] and participants who were continent [adjusted OR: 0.25, 95% CI (0.07-0.91)]. CONCLUSIONS: People with ID fall at a younger age compared with the broader community. The associated falls risk factors also differ to older community-dwelling adults. Health professionals should prioritise assessment and management of falls risk in this population.

Nuts and Cardiovascular Disease Prevention.

PURPOSE OF REVIEW: We review recent epidemiological and clinical studies investigating the consumption of tree nuts and peanuts and cardiovascular disease (CVD) mortality as well as CVD risk factors. RECENT FINDINGS: A greater consumption of tree nuts and peanuts is associated with a reduced risk of CVD mortality, as well as lower CVD events. Furthermore, risk factors associated with the development of CVD such as dyslipidemia, impaired vascular function, and hypertension are improved with regular tree nut and peanut consumption through a range of mechanism associated with their nutrient-rich profiles. There is weak inconsistent evidence for an effect of nut consumption on inflammation. There is emerging evidence that consuming tree nuts reduces the incidence of non-alcoholic fatty liver disease (NAFLD) and promotes diversity of gut microbiota, which in turn may improve CVD outcomes. Evidence for CVD prevention is strong for some varieties of tree nuts, particularly walnuts, and length of supplementation and dose are important factors for consideration with recommendations.

RESPOND: a patient-centred programme to prevent secondary falls in older people presenting to the emergency department with a fall-protocol for a mixed methods programme evaluation.

BACKGROUND: Programme evaluations conducted alongside randomised controlled trials (RCTs) have potential to enhance understanding of trial outcomes. This paper describes a multi-level programme evaluation to be conducted alongside an RCT of a falls prevention programme (RESPOND). OBJECTIVES: (1) To conduct a process evaluation in order to identify the degree of implementation fidelity and associated barriers and facilitators. (2) To evaluate the primary intended impact of the programme: participation in fall prevention strategies and the factors influencing participation. (3) To identify the factors influencing RESPOND RCT outcomes: falls, fall injuries and emergency department (ED) re-presentations. METHODS/DESIGN: 528 community-dwelling adults aged 60-90 years presenting to two EDs with a fall will be recruited and randomly assigned to the intervention or standard care group. All RESPOND participants and RESPOND clinicians will be included in the evaluation. A mixed methods design will be used and a programme logic model will frame the evaluation. Data will be sourced from interviews, focus groups, questionnaires, clinician case notes, recruitment records, participant-completed calendars, hospital administrative datasets and audio-recordings of intervention contacts. Quantitative data will be analysed via descriptive and inferential statistics and qualitative data will be interpreted using thematic analysis. DISCUSSION: The RESPOND programme evaluation will provide information about contextual and influencing factors related to the RESPOND RCT outcomes. The results will assist researchers, clinicians and policy makers regarding decisions about future falls prevention interventions. Insights gained may be applicable to a range of chronic conditions where similar preventive intervention approaches are indicated. TRIAL REGISTRATION NUMBER: This programme evaluation is linked to the RESPOND RCT which is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000336684).

Diagnostics for resource-limited settings in the era of interferon-free HCV therapy.

The field of hepatitis C (HCV) therapy is moving inexorably towards a time when interferon is no longer part of routine HCV treatment. 2015 will see at least two interferon-free directly acting antiviral (DAA) treatments licensed in Europe and the USA. For those parts of the world that can afford it, this will mean the potential for treatment of those who have either failed interferon-based therapy or have been unable to tolerate the side-effects that commonly accompany treatment.

RESPOND--A patient-centred programme to prevent secondary falls in older people presenting to the emergency department with a fall: protocol for a multicentre randomised controlled trial.

INTRODUCTION: Participation in falls prevention activities by older people following presentation to the emergency department (ED) with a fall is suboptimal. This randomised controlled trial (RCT) will test the RESPOND programme, an intervention designed to improve older persons' participation in falls prevention activities through delivery of patient-centred education and behaviour change strategies. DESIGN AND SETTING: A RCT at two tertiary referral EDs in Melbourne and Perth, Australia. PARTICIPANTS: 528 community-dwelling people aged 60-90 years presenting to the ED with a fall and discharged home will be recruited. People who require an interpreter or hands-on assistance to walk; live in residential aged care or >50 km from the trial hospital; have terminal illness, cognitive impairment, documented aggressive behaviour or a history of psychosis; are receiving palliative care or are unable to use a telephone will be excluded. METHODS: Participants will be randomly allocated to the RESPOND intervention or standard care control group. RESPOND incorporates (1) a home-based risk factor assessment; (2) education, coaching, goal setting and follow-up telephone support for management of one or more of four risk factors with evidence of effective interventions and (3) healthcare provider communication and community linkage delivered over 6 months. Primary outcomes are falls and fall injuries per person-year. DISCUSSION: RESPOND builds on prior falls prevention learnings and aims to help individuals make guided decisions about how they will manage their falls risk. Patient-centred models have been successfully trialled in chronic and cardiovascular disease; however, evidence to support this approach in falls prevention is limited. TRIAL REGISTRATION NUMBER: The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000336684).

Nutrient displacement associated with walnut supplementation in men.

BACKGROUND: Dietary guidance issued by various global government agencies recommends nut consumption within the context of a healthy-eating pattern. Nuts are nutrient dense and may promote nutrient adequacy. As an energy-dense food, nuts must replace other foods in the diet to prevent an excess of calories. METHODS: We evaluated how recommending the inclusion of walnuts (75 g day(-1) ) in the diet affected energy and nutrient intake in men (45-75 years; mean body mass index = 27.6 kg m(-2) ; n = 19) at risk for developing prostate cancer. Guidance was provided about incorporating walnuts isocalorically in a healthy diet. Three-day food records and body weight were collected at baseline and after two 8-week diet periods (usual versus walnut supplement diets). RESULTS: Energy intake on the walnut supplement diet exceeded the usual diet, although body weight was maintained. Energy intake was lower on the actual walnut supplement diet than the calculated walnut diet [10,865 kJ (2595 kcal) versus 11,325 kJ (2705 kcal) per day, respectively] and contributed 23% less energy than 75 g of walnuts. Approximately, 86% and 85% of the total fat and saturated fatty acids from walnuts were not displaced, whereas the increase in fibre from the usual diet to the actual walnut supplement diet represented less than one-half (39%) of the fibre provided by 75 g of walnuts. Walnuts were substituted, in part, for other foods, and the nutrient profile of the diet was improved, however, the beneficial effect of walnuts on the diet quality was not optimized. CONCLUSIONS: Individuals do not optimally implement food-based guidance. Consequently, nutrition professionals play a key role in teaching the implementation of food-based recommendations.

Multidisciplinary staff perceived barriers and enablers to early mobilization of patients with burns in the ICU.

BACKGROUND: Complex challenges face clinicians managing critically ill patients with burns, particularly in the context of enhancing outcomes after a stay in ICU. Compounding this, a dearth of research explores the specific and modifiable factors that impact early mobilization in the ICU environment. AIM: To explore the barriers and enablers of early functional mobilization for patients with burns in the ICU from a multidisciplinary perspective. DESIGN: A qualitative phenomenological study. METHODS: Semi-structured interviews supplemented by online questionnaires conducted with 12 multidisciplinary clinicians (four doctors, three nurses and five physical therapists) who previously managed burn patients at a quaternary level ICU. Data were thematically analysed. RESULTS: Four main themes: patient, ICU clinicians, the workplace and the physical therapist were identified as impacting on early mobilization. Subthemes identified barriers or enablers to mobilization but all were strongly influenced by overarching theme of the clinician's "emotional filter." Barriers included high levels of pain, heavy sedation and low levels of clinician exposure to treating patients with burns. Enablers included higher levels of clinician's experience and knowledge about burn management and benefits of early mobilization; increased coordinated staff resources when undertaking mobilization; and, open communication and positive culture towards early mobilization across the multidisciplinary team. CONCLUSION: Patient, clinician and workplace barriers and enablers were identified to influencing the likelihood of achieving early mobilization of patients with burns in the ICU. Emotional support for staff through multidisciplinary collaboration and development of structured burns training program were key recommendations to address barriers and strengthen enablers to early mobilization of patients with burns in the ICU.

Heterogeneity of reporting standards in randomised clinical trials of endovenous interventions for varicose veins.

AIMS: The efficacy of endovenous treatments for venous reflux has been demonstrated in numerous randomised clinical trials, although significant heterogeneity may exist between studies. The aim of this study was to assess the heterogeneity in reporting between randomised clinical trials investigating endovenous treatments for patients with varicose veins. METHODS: A literature search of the Pubmed, Cochrane and Google Scholar databases was performed using appropriate search terms. Randomised clinical trials published between January 1968 and June 2009 evaluating endovenous interventions for varicose veins were included and relevant abstracts and full text articles were reviewed. Published study reports were evaluated against recommended reporting standards published by the American Venous Forum in 2007. RESULTS: Twenty-eight randomised trials fulfilled the inclusion criteria. Median patient age (reported in 20/28 studies) ranged from 33 to 54 years. The CEAP classification was presented in 17/28 studies and the proportion of patients with C2 disease ranged from 6.3% to 83.5%. A total of 31 different outcome measures were utilised. This included 13 different questionnaires, varicose vein recurrence at 38 time points and 30 categories of complications. Duplex ultrasonography was used in 21/28 trials to assess recurrence. Quality of life was only evaluated in 11 studies and the follow-up period ranged from 3 weeks to 10 years. CONCLUSIONS: Meaningful comparison across randomised studies of endovenous treatments is made difficult by considerable variations in study populations and outcome measures between trials. This highlights the need for the use of prospectively agreed population selection, and reporting standards for outcome measures in randomised clinical assessments of new treatments.

Is it worthwhile to offer repeat hydrodilatation for frozen shoulder after 6 weeks?

AIMS: Frozen shoulder is a common problem for which hydrodilatation is an established treatment option although the optimal regime is not yet established. We asked 'is it worthwhile to offer a repeat hydrodilatation procedure after 6 weeks?' METHODS: A total of 36 patients diagnosed with frozen shoulder and undergoing hydrodilatation were evaluated. All patients had an initial hydrodilatation and were offered a repeat procedure after 6 weeks. Of the total patients, 22 chose to undergo a repeat procedure. The Shoulder Disability Questionnaire UK Score and Oxford Shoulder Score were used to evaluate pre- and postprocedure outcome. The mean follow up was 15.4 months. RESULTS: The Oxford Shoulder Score improved by a significant level after both single (30.5-17.1) and repeat hydrodilatation (36.0-21.4). No significant change was observed after either procedure when using the Shoulder Disability Questionnaire UK Score as an outcome measure. CONCLUSIONS: The data are suggestive that routine hydrodilatation after 6 weeks is not appropriate and should be instead offered to those patients who can tolerate it and who have not fully benefitted after a single procedure.

Microtubule dynamics investigated by microinjection of Paramecium axonemal tubulin: lack of nucleation but proximal assembly of microtubules at the kinetochore during prometaphase.

Microtubule (MT) dynamics in PtK2 cells have been investigated using in vivo injection of unmodified Paramecium ciliary tubulin and time-lapse fixation. The sites of incorporation of the axonemal tubulin were localized using a specific antibody which does not react with vertebrate cytoplasmic tubulin (Adoutte, A., M. Claisse, R. Maunoury, and J. Beisson. 1985. J. Mol. Evol. 22:220-229), followed by immunogold labeling, Nanovid microscopy, and ultrastructural observation of the same cells. We confirm data from microinjection of labeled tubulins in other cell types (Soltys, B. J., and G. G. Borisy. 1985. J. Cell Biol. 100:1682-1689; Mitchison, T., L. Evans, E. Schulze, and M. Kirschner. 1986. Cell. 45:515-527; Schulze, E., and M. Kirschner. 1986. J. Cell Biol. 102:1020-1031). In agreement with the dynamic instability model (Mitchison, T., and M. Kirschner. 1984. Nature (Lond.). 312:237-242), during interphase, fast (2.6 microns/min) distal growth of MTs occurs, together with new centrosomal nucleation. Most of the cytoplasmic MT complex is replaced within 15-30 min. During mitosis, astral MTs display the same pattern of renewal, but the turnover of the MT system is much faster (approximately 6 min). We have concentrated on the construction of the kinetochore fibers during prometaphase and observe that (a) incorporation of tubulin in the vicinity of the kinetochores is not seen during prophase and early prometaphase as long as the kinetochores are not yet connected to a pole by MTs; (b) proximal time-dependent incorporation occurs only into preexisting kinetochore MTs emanating from centrosomes. Consequently, in undisturbed prometaphase cells, the kinetochores probably do not act as independent nucleation sites. This confirms a model in which, at prometaphase, fast probing centrosomal MTs are grabbed by the kinetochores, where tubulin incorporation then takes place.

Regulation of microtubule dynamics and nucleation during polarization in MDCK II cells.

MDCK cells form a polarized epithelium when they reach confluence in tissue culture. We have previously shown that concomitantly with the establishment of intercellular junctions, centrioles separate and microtubules lose their radial organization (Bacallao, R., C. Antony, C. Dotti, E. Karsenti, E.H.K. Stelzer, and K. Simons. 1989. J. Cell Biol. 109:2817-2832. Buendia, B., M.H. Bré, G. Griffiths, and E. Karsenti. 1990. 110:1123-1136). In this work, we have examined the pattern of microtubule nucleation before and after the establishment of intercellular contacts. We analyzed the elongation rate and stability of microtubules in single and confluent cells. This was achieved by microinjection of Paramecium axonemal tubulin and detection of the newly incorporated subunits by an antibody directed specifically against the Paramecium axonemal tubulin. The determination of newly nucleated microtubule localization has been made possible by the use of advanced double-immunofluorescence confocal microscopy. We have shown that in single cells, newly nucleated microtubules originate from several sites concentrated in a region localized close to the nucleus and not from a single spot that could correspond to a pair of centrioles. In confluent cells, newly nucleated microtubules were still more dispersed. The microtubule elongation rate of individual microtubules was not different in single and confluent cells (4 microns/min). However, in confluent cells, the population of long lived microtubules was strongly increased. In single or subconfluent cells most microtubules showed a t1/2 of less than 30 min, whereas in confluent monolayers, a large population of microtubules had a t1/2 of greater than 2 h. These results, together with previous observations cited above, indicate that during the establishment of polarity in MDCK cells, microtubule reorganization involves both a relocalization of microtubule-nucleating activity and increased microtubule stabilization.

A biomechanical basis for tears of the human acetabular labrum.

OBJECTIVE: Acetabular labral tears predominantly affect young patients and are a source of hip pain in the athlete. Four causes of the initiation of labral tears have been proposed; trauma, hypolaxity of the anterior capsule, dysplasia and bony impingement. A further cause could be reduced biomechanical properties in the area most susceptible to tears. However, no work has defined these properties. DESIGN: 32 compressive and 32 tensile test samples were harvested from fresh-frozen cadaveric acetabula. The labrum was divided into eight areas to allow comparison around its circumference. Semiconfined compressive testing and tensile testing were performed at a displacement rate of 10 mm/min in a controlled environment of 100% humidity at 37 (SD 1) degrees C. SETTING: Cadaveric study. RESULTS: The mean compressive stiffness was 31.75 (SD 16.7) MPa, and the mean tensile elastic modulus was 24.7 (SD 10.8) MPa. The anterosuperior region had a significantly lower compressive elastic modulus than either of the posterior quadrants (p<0.05) and a significantly lower tensile modulus to the anterioinferior area (p<0.05). CONCLUSIONS: The biomechanical properties in the anterosuperior region may be a contributing factor to the initiation of labral tears.

Improvised explosive devices: pathophysiology, injury profiles and current medical management.

The improvised explosive device (IED), in all its forms, has become the most significant threat to troops operating in Afghanistan and Iraq. These devices range from rudimentary home made explosives to sophisticated weapon systems containing high-grade explosives. Within this broad definition they may be classified as roadside explosives and blast mines, explosive formed pojectile (EFP) devices and suicide bombings. Each of these groups causeinjury through a number of different mechanisms and can result in vastly different injury profiles. The "Global War on Terror" has meant that incidents which were previously exclusively seen in conflict areas, can occur anywhere, and clinicians who are involved in emergency trauma care may be required to manage casualties from similar terrorist attacks. An understanding of the types of devices and their pathophysiological effects is necessary to allow proper planning of mass casualty events and to allow appropriate management of the complex poly-trauma casualties they invariably cause. The aim of this review article is to firstly describe the physics and injury profile from these different devices and secondly to present the current clinical evidence that underpins their medical management.

Blast mines: physics, injury mechanisms and vehicle protection.

Since World War II, more vehicles have been lost to land mines than all other threats combined. Anti-vehicular (AV) mines are capable of disabling a heavy vehicle, or completely destroying a lighter vehicle. The most common form of AV mine is the blast mine, which uses a large amount of explosive to directly damage the target. In a conventional military setting, landmines are used as a defensive force-multiplier and to restrict the movements of the opposing force. They are relatively cheap to purchase and easy to acquire, hence landmines are also potent weapons in the insurgents' armamentarium. The stand-offnature of its design has allowed insurgents to cause significant injuries to security forces in current conflicts with little personal risk. As a result, AV mines and improvised explosive devices (IEDs) have become the most common cause of death and injury to Coalition and local security forces operating in Iraq and Afghanistan. Detonation of an AV mine causes an explosive, exothermic reaction which results in the formation of a shockwave followed by a rapid expansion of gases. The shockwave is mainly reflected by the soillair interface and fractures the soil cap overthe mine. The detonation products then vent through the voids in the soil, resulting in a hollow inverse cone which consists of the detonation gases surrounded by the soil ejecta. It is the combination of the detonation products and soil ejecta that interact with the target vehicle and cause injury to the vehicle occupants. A number of different strategies are required to mitigate the blast effects of an explosion. Primary blast effects can be reduced by increasing the standoff distance between the seat of the explosion and the crew compartment. Enhancement of armour on the base of the vehicle, as well as improvements in personal protection can prevent penetration of fragments. Mitigating tertiary effects can be achieved by altering the vehicle geometry and structure, increasing vehicle mass, as well as developing new strategies to reduce the transfer of the impulse through the vehicle to the occupants. Protection from thermal injury can be provided by incorporating fire resistant materials into the vehicle and in personal clothing. The challenge for the vehicle designer is the incorporation of these protective measures within an operationally effective platform.

Tensile properties of the human glenoid labrum.

Human fresh-frozen cadaveric glenoid labrae from 16 donors were harvested and ten of these had no gross degeneration. These ten were divided into eight equal circumferential sections. Each section was cut to produce test-samples from the core layer with a cross-section of 1 x 1 mm. Tensile testing was performed within a controlled environment unit at 37 +/- 1 degrees C and 100% relative humidity. Each test-sample was precycled to a quasi-static state to alleviate the effects of deep-freezing, prior to final testing. The tangent modulus was calculated for each test-sample before and after a 5-min period of stress relaxation and at yield. The mean elastic modulus and yield stress of the glenoid labrum were 22.8 +/- 11.4 and 2.5 +/- 2.1 MPa, respectively. The anterosuperior portion had a lower elastic modulus and lower yield stress than the inferior portion (both P < 0.02). The pre-stress relaxation tangent modulus was significantly lower than the post-stress relaxation tangent modulus for all portions of the labrum. The glenoid labrum has similar tensile material properties to articular cartilage. Its elastic modulus varies around its circumference. This suggests that the labrum may encounter different forces at different positions.

Collagenous microstructure of the glenoid labrum and biceps anchor.

The glenoid labrum is a significant passive stabilizer of the shoulder joint. However, its microstructural form remains largely unappreciated, particularly in the context of its variety of functions. The focus of labral microscopy has often been histology and, as such, there is very little appreciation of collagen composition and arrangement of the labrum, and hence the micromechanics of the structure. On transmission electron microscopy, significant differences in diameter, area and perimeter were noted in the two gross histological groups of collagen fibril visualized; this suggests a heterogeneous collagenous composition with potentially distinct mechanical function. Scanning electron microscopy demonstrated three distinct zones of interest: a superficial mesh, a dense circumferential braided core potentially able to accommodate hoop stresses, and a loosely packed peri-core zone. Confocal microscopy revealed an articular surface fine fibrillar mesh potentially able to reduce surface friction, bundles of circumferential encapsulated fibres in the bulk of the tissue, and bone anchoring fibres at the osseous interface. Varying microstructure throughout the depth of the labrum suggests a role in accommodating different types of loading. An understanding of the labral microstructure can lead to development of hypotheses based upon an appreciation of this component of material property. This may aid an educated approach to surgical timing and repair.

Qualitative and quantitative descriptions of glenohumeral motion.

Joint modelling plays an important role in qualitative and quantitative descriptions of both normal and abnormal joints, as well as predicting outcomes of alterations to joints in orthopaedic practice and research. Contemporary efforts in modelling have focussed upon the major articulations of the lower limb. Well-constrained arthrokinematics can form the basis of manageable kinetic and dynamic mathematical predictions. In order to contain computation of shoulder complex modelling, glenohumeral joint representations in both limited and complete shoulder girdle models have undergone a generic simplification. As such, glenohumeral joint models are often based upon kinematic descriptions of inadequate degrees of freedom (DOF) for clinical purposes and applications. Qualitative descriptions of glenohumeral motion range from the parody of a hinge joint to the complex realism of a spatial joint. In developing a model, a clear idea of intention is required in order to achieve a required application. Clinical applicability of a model requires both descriptive and predictive output potentials, and as such, a high level of validation is required. Without sufficient appreciation of the clinical intention of the arthrokinematic foundation to a model, error is all too easily introduced. Mathematical description of joint motion serves to quantify all relevant clinical parameters. Commonly, both the Euler angle and helical (screw) axis methods have been applied to the glenohumeral joint, although concordance between these methods and classical anatomical appreciation of joint motion is limited, resulting in miscommunication between clinician and engineer. Compounding these inconsistencies in motion quantification is gimbal lock and sequence dependency.

The effects of lamivudine treatment on HIV-1 disease progression are highly correlated with plasma HIV-1 RNA and CD4 cell count.

OBJECTIVE: To determine the value of plasma HIV-1 RNA and CD4 cell count as predictors of the clinical benefit of antiretroviral treatment. DESIGN AND SETTING: The CAESAR (Canada, Australia, Europe, South Africa) trial randomized 1840 patients [inclusion CD4 cell count, 25-250 x 10(6)/l] to add either placebo, lamivudine (3TC) or 3TC plus loviride in a double-blinded fashion to baseline treatments (zidovudine, zidovudine-didanosine or zidovudine-zalcitabine) for 1 year. PATIENTS: This analysis included 487 patients with data on CD4 cell count and HIV-1 RNA after 12-20 weeks of treatment and subsequent follow-up for clinical progression. MAIN OUTCOME MEASURES: The correlation between 12-20-week change in CD4 cell count, HIV-1 RNA and progression to AIDS or death in the placebo group was used to predict the clinical benefit of the 3TC-containing arms of the trial, given their effects on CD4 cell count and HIV-1 RNA. RESULTS: After 12-20 weeks of treatment, HIV-1 RNA fell by 0.37 log10 copies/ml in the 3TC arms versus a rise of 0.05 log10 copies/ml in the placebo arm. The 12-20-week CD4 cell count rose by 35 x 10(6)/l in the 3TC arm versus a fall of 8 x 10(6)/l in the placebo arm. After 12-20 weeks of treatment, a reduction in HIV-1 RNA of 1 log10 at 12-20 weeks predicted a 49% reduction in progression [hazard ratio (HR), 0.51; 95% confidence interval (CI), 0.30-0.87] and a rise in CD4 cell count of 50 x 10(6)/l predicted a 51% reduction in progression (HR, 0.49; 95% CI, 0.33-0.73). Using the model from the placebo arm, the rises in CD4 cell count and reductions in HIV-1 RNA during 3TC treatment predicted a 59% reduction in progression to AIDS or death. The observed clinical benefit was a 57% reduction in progression for the 3TC arms versus placebo (HR, 0.43; 95% CI, 0.26-0.71). CONCLUSIONS: Rises in CD4 cell count and reductions in HIV-1 RNA were reliable in predicting the clinical benefit of 3TC in the CAESAR trial.