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BACKGROUND This multicentre cohort study investigates the effect of smoking on the outcome of rotator cuff repair (RCR), with attention to age at presentation for surgery, pre-operative and post-operative pain and function and intra-operative findings. METHODS Patient information was collected pre-operatively, including Flex Shoulder Function (Flex SF) and visual analogue scale pain, then at 6 months, 1, 2 and 5 years post-operatively. Intra-operative technical data were collected by the operating surgeon. Current smokers were classified by daily cigarette consumption. RESULTS A total of 1383 RCRs in as many patients were included with an 84% 5-year follow-up. Smokers were on average 6.7 years younger than non-smokers (51.8 vs. 58.5, P

BackgroundImpetigo is a common and contagious bacterial skin infection, affecting children worldwide but it is particularly prevalent in deprived communities. In New Zealand widespread prescribing of the topical antibiotic fusidic acid had led to an increase in antimicrobial resistance of Staphylococcus aureus. Alternative treatments are urgently being sought and as impetigo is a superficial infection, it has been suggested that topical antiseptics such as hydrogen peroxide or simple wound care alone may treat impetigo while avoiding the risk of increased antimicrobial resistance.MethodsThis protocol for a non-inferiority, single-blind randomised controlled trial compares topical fusidic acid with topical hydrogen peroxide and with simple wound care in the treatment of childhood impetigo. Participants are randomised to one of the three treatments for five days and the primary outcome is clinical improvement. This is assessed through paired photographs analysed by graders blinded to treatment arm. The trial is based in school health clinics in an urban centre in New Zealand. Comparison of antimicrobial resistance patterns pre- and post-treatment is also performed.DiscussionSpecial note is made of the need to involve the communities most affected by impetigo in the design and implementation of the clinical trial in order to recruit the children most in need of safe and effective treatments.Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) 12616000356460

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Main objective: To assess the effects of acute assessment services on patient flow following attendance at a hospital emergency department. Secondary objectives: To assess whether the effects of acute assessment services differ according to the specialty population they serve (medicine‐only versus surgery‐only versus combined services). To assess whether the effects of acute assessment services differ depending on access pathways for patients (direct access to the service at or before the point of triage versus access via ED provider referral).

We implement jackknife model averaging (JMA) and a new prediction technique—hybrid-boost model averaging (HbMA)—to a surgical dataset that includes categorical explanatory variables. The model requirements for HbMA are different to that for JMA. HbMA generally does not require decent models to be included in the model average. However, the utility of HbMA is limited by the possibility of multiple solutions for the HbMA weights. Both model averaging approaches are comparable under the appropriate conditions. Among all the model averages considered, the best jackknife model average gives slightly better predictions of the surgery durations than the best hybrid-boost model average when evaluated on our surgical dataset. Finally, we discuss several methods that may further improve the performance of HbMA.

Background This study is a collation of baseline demographic characteristics of those presenting for rotator cuff repair in New Zealand, and exploration of associations with preoperative function and pain. Data were obtained from the New Zealand Rotator Cuff Registry; a multicentre, nationwide prospective cohort of rotator cuff repairs undertaken from 1 March 2009 until 31 December 2010. Methods A total of 1383 patients were included in the study. This required complete demographic information, preoperative Flex-SF (functional score) and pain scores. Following univariate analysis, a multivariate model was used. Results The average age was 58 years (69% males and 11% smokers). New Zealand Europeans made up 90% and Maori 5%. The average preoperative Flex-SF was significantly lower (poorer function) in those over 65 years, females, smokers and Maori, in the non-dominant patients, using a multivariate model. Average preoperative pain scores were significantly worse (higher scores) in females, Maori, Polynesians, smokers, using a multivariate model. Conclusion This is the largest reported prospective cohort of patients presenting for rotator cuff surgery. Results can be used to understand the effect of rotator cuff tears on the different patients, for example Maori patients who are under-represented, present younger, with more pain and poorer function.

During an expansion of the General Medicine (GM) department at Waitakere Hospital, a new roster was required for its teams. Patients being transferred to another hospital due to uneven patient workloads between the teams were identified as an issue that could be addressed by an improved roster. A more even distribution of patients among the teams is desirable because it is fairer for the staff and it also improves the continuity of care for patients. Continuity of care is improved by balanced workloads because fewer patients need to be transferred from teams with high workloads. A novel rostering technique, using a mixed integer programme (MIP), which uses past data on patient admissions to track team workloads, was implemented. This allowed multiple rosters for different configurations of admitting teams to be created and evaluated against past data traces, in terms of the difference in workloads of the teams and estimated ward occupancies. The best performing of the constructed rosters reduced the median difference in workload between the team with the most patients and the team with the fewest from 14.5 to 12.5 (13.8% reduction) for the data traces considered, when compared with a roster from an internal rostering group. Waitakere Hospital has put this roster in place and has observed a reduction in the variation in workload between the teams, with fewer patients being transferred to other hospitals due to high team workloads. These improvements cannot be solely attributed to rostering improvements, as other factors such as an increase in the number of inpatient teams have also contributed. However, the generation and evaluation of multiple different rosters via MIP was central to the process that determined the final configuration of the GM department.

This paper presents a case study of research conducted to improve the delivery of treatment to high priority cancer patients. The authors present a modelling framework that uses time-stamp data collected by the North Shore Hospital IT systems as “business as usual”, to describe the patient journey through the cancer-care process. A simulation process is developed that uses this data to estimate the service's performance under current operating practices, and enables “what-if” analysis to identify where changes to current practice can most effectively be applied, ensuring the investment of additional resource can be targeted at the steps of the patient pathway where it can result in the greatest improvement. The process is illustrated using the Breast Cancer stream as a case-study, for the initial study period (July 2013 to June 2014), with a follow-up analysis presented briefly for the 3 months from July to the end of September 2014.

Tactile feedback in recent decades has allowed humans to receive information through technology beyond traditional visual and auditory senses. Lateral skin stretch has the potential to be a mode of tactile feedback, reliably enabling the perception of directional cues through the use of a single actuator. Experiments were conducted to explore sensitivity to skin stretch on nine locations on the human lower leg. Thirty-two stimuli were presented to subjects, exploring effects of displacement (from 0.2-2.0 mm) and speed (from 0.5-4.0 mm/s) on the perception of left and right directions. Higher accuracy came from stimuli having higher displacements and speeds. Three of the locations: soleus, calcaneal tendon (upper), and fibularis longus (lower) all had a mean accuracy of at least 85 percent and are suitable locations for a skin stretch tactile feedback device.

Aim This study aims to describe the microbiology of middle ear fluid (MEF) in a cohort of children vaccinated with Streptococcus pneumoniae conjugate vaccine (PCV7) having ventilation tube insertion. Nasopharyngeal (NP) carriage of otopathogens in these children is compared with children without history of otitis media. Methods Between May and November 2011, MEF and NP samples from 325 children aged

Periprosthetic osteolysis in the retroacetabular region with cancellous bone loss is a recognized phenomenon in the long-term follow-up of total hip replacement. The effects on load transfer in the presence of defects are less well known. A finite element model incorporating a retroacetabular defect behind a cementless component was validated against a 4th generation sawbone pelvis. Computational predictions of surface strain and von Mises stresses were closely correlated to experimental findings. The presence of a cancellous defect increased von Mises stress in the cortical bone of the medial wall of the pelvis. At a load of 600 N this was under the predicted failure stress for cortical bone. Increases in the cup size relative to the acetabulum caused increased stress in the cortical bone of the lateral wall of the pelvis, adjacent to the acetabulum. We are confident that our modeling approach can be applied to patient specific defects to predict pelvis stress with large loads and a range of activities.

Background: Rotator cuff-tear arthropathy has traditionally represented a challenge to the shoulder arthroplasty surgeon. The poor results of conventional total shoulder arthroplasty in rotator-cuff-deficient shoulders due to glenoid component loosening have led to hemiarthroplasty being the traditional preferred surgical option. Recently, reverse total shoulder arthroplasty has gained increasing popularity because of a clinical perception of an improved functional outcome, despite the lack of comparative data. The aim of this study was to compare the early functional results of hemiarthroplasty with those of reverse shoulder arthroplasty in the management of cuff-tear arthropathy. Methods: The results of 102 primary hemiarthroplasties for rotator cuff-tear arthropathy were compared with those of 102 reverse shoulder arthroplasties performed for the same diagnosis. Patients were identified from the New Zealand Joint Registry and matched for age, sex, and American Society of Anesthesiologists (ASA) scores. Oxford Shoulder Scores (OSS) collected at six months postoperatively as well as mortality and revision rates were compared between the two groups. Results: There were fifty-one men and fifty-one women in each group, with a mean age of 71.6 years in the hemiarthroplasty group and 72.6 years in the reverse shoulder arthroplasty group. The mean OSS at six months was 31.1 in the hemiarthroplasty group and 37.5 in the reverse shoulder arthroplasty group. At the time of follow-up, there were nine revisions in the hemiarthroplasty group and five in the reverse shoulder arthroplasty group. No difference in mortality rate was seen between the two groups. Conclusions: In this unselected population with rotator cuff-tear arthropathy, controlled for age, sex, and ASA score, reverse shoulder arthroplasty resulted in a functional outcome that was superior to that of hemiarthroplasty. Longer-term follow-up is needed to confirm these findings. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Bone mineral density (BMD) in the proximal tibia decreases after TKA and is believed to be a factor in implant migration and loosening. Unicompartmental knee arthroplasty (UKA) is a less invasive procedure preserving knee compartments unaffected by degeneration. Finite element studies have suggested UKA may preserve BMD and that implants of differing stiffnesses might differentially affect BMD but these notions have not been clinically confirmed.We therefore asked whether (1) proximal tibial BMD decreases after UKA, and (2) a cemented metal tibial component with a mobile polyethylene (PE) bearing would have greater BMD loss than a cemented PE tibial component.We prospectively followed 48 patients who underwent 50 UKAs using one of two implants: one with a cemented metal tibial baseplate and a mobile PE insert (n = 26) and one with a cemented all-PE tibial component (n = 24). In followup we assessed pain and function (Oxford Knee Score, SF-12, The Knee Society Score(©)) and radiographs. BMD changes were assessed using quantitative CT osteodensitometry performed postoperatively and at 1 and 2 years after the index procedure.Mean cancellous BMD decreased 1.9% on the medial side and 1.1% on the lateral side. Mean cortical BMD was static, decreasing 0.4% on the medial side and increasing 0.5% on the lateral side. The greatest observed difference between implants for any region was 3.7%. There were no differences in pain or functional outcome scores.BMD was preserved 2 years after UKA with no major differences seen between implant types.

Study design Blinded radiographic analysis of CT scans reformatted for precise lumbar spinous process (LSP) measurement.

Little is known about tibial bone remodeling with TKA and its clinical relevance. We performed a randomized clinical trial to compare tibial bone density changes in cemented components with different bearing designs. Bone density changes were assessed using quantitative computed tomography (qCT)-assisted osteodensitometry. Twenty-eight rotating-platform and 26 fixed-platform cemented TKAs were included. The nonoperated contralateral side was used as a control. CT scans were performed postoperatively and 1 year and 2 years after the index operation. Cancellous bone density loss (up to 12.6% at 2 years) was observed in all proximal tibial regions in both cohorts. In contrast, we found lower cortical bone density loss (up to 3.6% at 2 years). We found no differences in bone loss between fixed- and rotating-platform implants. The decrease of cancellous bone density after TKA suggests stress transfer to the cortical bone.

The number of periprosthetic fractures following total hip arthroplasty (THA) is increasing. There is, however, limited data on the functional outcome following these injuries. We analyzed functional outcome for revision THA following periprosthetic fracture, and compared this to the outcome of elective revision THA performed for aseptic loosening.232 patients undergoing revision THA for femoral fracture were identified from the New Zealand National Registry. Functional outcome was measured using the Oxford 12 hip score (OHS). A reference group of 232 patients undergoing elective revision THA was selected and matched for age and sex.Outcome was worse following revision THA for periprosthetic fracture than in reference patients (mean OHS: 29 vs. 24, p = 0.006). A higher 6-month mortality rate was seen in periprosthetic fracture patients (7.3% vs. 0.9%, p0.001), along with a higher likelihood of re-revision (7.3% vs. 2.6%, p = 0.06).This large comparative series of periprosthetic fractures following THA shows that patients with periprosthetic fracture have poorer functional outcome and higher death rates than patients undergoing revision THA for aseptic loosening.

Five hundred orthopaedic surgeons and 336 anaesthetists were surveyed to assess current UK attitudes towards transfusion practice following arthroplasty surgery. Seventy-two percent of surgeons and 73% of anaesthetists responded to the survey. In an uncomplicated patient following total hip arthroplasty, 53.2% of surgeons and 63.1% of anaesthetists would transfuse at or below a haemoglobin (Hb) level of 8 g/dL. Surgeons tended to be more aggressive in their attitudes, with a mean transfusion threshold of 8.3 g/dL compared to 7.9 g/dL for anaesthetists (p

Background: Nonoperative treatment of idiopathic clubfoot has become increasingly accepted worldwide as the initial standard of care. The Ponseti method has become particularly popular as a result of published short and long-term success rates in North America. The purpose of the current study was to examine the early rate of clubfoot recurrence following the use of the Ponseti treatment method in a New Zealand population and to analyze patient characteristics to identify factors predictive of recurrence. Methods: Fifty-one consecutive babies with a total of seventy-three clubfeet treated by the Ponseti technique were followed prospectively for a minimum of two years from the start of treatment. Recurrence, defined as the need for any subsequent operative treatment, was analyzed with respect to the severity at presentation, the time of presentation, the number of casts needed to obtain the initial correction, any family history of clubfoot, ethnicity, and the compliance with postcorrection abduction bracing. Recurrence was classified as minor, defined as requiring a tendon transfer or an Achilles tendon lengthening, or major, defined as requiring a full posterior or posteromedial surgical release to achieve a corrected plantigrade foot. Results: Twenty-one (41%) of the fifty-one patients had a recurrence, which was major in twelve of them and minor in nine. The parents of twenty-six babies (51%) complied with the abduction bracing protocol, and only three of these children had a major recurrence. Compliance with abduction bracing was associated with the greatest risk reduction for recurrence (odds ratio, 0.2; p = 0.009). When the parents had not complied with the bracing protocol, the patient had a five times greater chance of having a recurrence. With the numbers studied, no significant relationships were found between recurrence and the severity at presentation, the time of presentation, the number of casts needed to obtain correction, ethnicity, or a family history of clubfoot. Conclusions: Compliance with the postcorrection abduction bracing protocol is crucial to avoid recurrence of a clubfoot deformity treated with the Ponseti method. When the parents comply with the bracing protocol, the Ponseti method is very effective at maintaining a correction, although minor recurrences are still common. When the parents do not comply with the bracing protocol, many major and minor recurrences should be expected. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

Background Recent literature has shown that Propionibacterium acnes can be cultured from superficial and deep layers of the shoulder. Our aims were to assess the rate of P. acnes colonization in patients undergoing primary shoulder arthroplasty, to identify patient-related risk factors, and to evaluate the efficacy of our perioperative antisepsis protocol. Methods Thirty consecutive patients undergoing primary shoulder arthroplasty were included in our study. Swabs were taken perioperatively (4 superficial and 2 deep wound swabs) and analyzed quantitatively for P. acnes . Cefazolin minimum inhibitory concentration was determined for P. acnes isolates from positive deep cultures. Results Twenty-two patients (73%) had positive cultures for P. acnes . Male gender ( P = .024) and presence of hair ( P = .005) had significantly higher rates of P. acnes superficial cultures. Subjects with positive superficial P. acnes cultures ( P = .076) and presence of hair with a history of steroid injection ( P = .092) were more likely to have deep P. acnes –positive cultures, but this was not statistically significant. Local topical antisepsis measures did not eradicate P. acnes ( P = .12). Mean cefazolin minimum inhibitory concentration for P. acnes was 0.32 μg/mL. Conclusion P. acnes is commonly isolated from the skin and deep surgical wounds of patients undergoing primary total shoulder arthroplasty who have not had previous shoulder surgery. Male gender and presence of hair were significant risk factors for P. acnes colonization. Perioperative local topical antisepsis and cefazolin administration were not effective in eliminating P. acnes colonization.

Background: Periprosthetic bone remodelling is an important issue in total hip arthroplasty, which can compromise long-term outcomes. The aim of this study was to evaluate bone remodelling of the proximal femur with an uncemented hydroxyapatite-coated taper stem. Methods: Twenty-three patients (27 hips) were included in this study. The mean age of the patients at the index operation was 57.2 years. There were 15 men and 8 women. Bone remodelling was assessed with quantitative computed tomography and the clinical outcome determined using the Harris Hip Scores. The mean preoperative Harris Hip Score was 38 points and at the 1-year follow up, it was rated 96 points. All hips were radiologically stable. Results: At the 1-year follow up, we found a greater bone-density loss of the cancellous bone (ranging from 16.7 to 28.2%) compared with the cortical bone (ranging from 5.3 to 7.8%). A strong correlation was found between the low density of the cortical bone at the index operation and a higher loss of bone density at the follow up. Conclusion: The newly designed tapered stem showed good clinical and radiological outcomes with a proximal femoral bone loss that compares favourably with other studies.

The object of this study was to develop a method to assess the accuracy of an image-free total knee replacement navigation system in legs with normal or abnormal mechanical axes. A phantom leg was constructed with simulated hip and knee joints and provided a means to locate the centre of the ankle joint. Additional joints located at the midshaft of the tibia and femur allowed deformation in the flexion/extension, varus/valgus and rotational planes. Using a digital caliper unit to measure the coordinates precisely, a software program was developed to convert these local coordinates into a determination of actual leg alignment. At specific points in the procedure, information was compared between the digital caliper measurements and the image-free navigation system. Repeated serial measurements were undertaken. In the setting of normal alignment the mean error of the system was within 0.5°. In the setting of abnormal plane alignment in both the femur and the tibia, the error was within 1°. This is the first study designed to assess the accuracy of a clinically-validated navigation system. It demonstrates in vitro accuracy of the image-free navigation system in both normal and abnormal leg alignment settings.

The classical world-views of discrete event simulation (DES) are event scheduling, activity scanning and process interaction. A fourth approach, the three-phase method, extends activity scanning and is often regarded as another world-view. These world-views provide the theoretical framework for applying DES in practice. However, in health care simulation, practitioners often face modeling challenges where the concepts and methodologies described by these world-views are not able to reflect either the dynamics or the entity flow of the system being modelled. This leads to individualized approaches and solutions that do not build on a unified and standardized theoretical basis. In this paper we present an extension to the activity scanning world-view based on the needs of the health care sector that uses hierarchical control structures as a more general, flexible and powerful tool to define health care DES models. To demonstrate the strength and potential of the approach two ongoing simulation studies are briefly outlined and the benefits of using the new world-view for these models is discussed. INTRODUCTION AND MOTIVATION In DES the underlying system is changed at discrete points in time. How these changes are modeled, controlled and triggered is dependent on the sub-domain of discrete event simulation, also known as the worldview, being utilized. The classical world-views are: event scheduling; activity scanning; and process interaction. However, the three phase method, which is an extension to the activity scanning approach, is also often referred to as a world-view. Much work has been done to formalize, evaluate, compare and transform the different world-views, as in (Balci 1988; Birta and Arbez 2007), or more recently (Overstreet and Nance

Background A number of grading systems for severity of clubfoot have been reported in the literature, but none are universally accepted. The aim of this study was to find the correlation between 2 of the most widely utilized classification systems (the Pirani score and the Dimeglio score) with number of Ponseti casts required to achieve initial clubfeet correction. Methods A retrospective study of prospectively collected data was performed. All clubfeet assessed at our dedicated clubfoot clinic from January 2007 to December 2011 were included. Clubfoot severity was assessed using both the Pirani score and the Dimeglio score. The total number of casts was calculated from the first cast to the time of initiation of the foot abduction orthosis. Results The mean number of Ponseti casts required to achieve initial correction was 5.8 (range, 2 to 10 casts). A low correlation (rs 0.21) was identified when the total Dimeglio score was compared with the number of casts. No correlation (rs 0.12) was identified between the Pirani score and the number of casts. Conclusions The Dimeglio and Pirani scores remain the most widely accepted clubfoot severity grading systems. However, their prognostic value remains questionable, at least in the early treatment stages. Level of evidence Prognostic study level II.

Proximal tibial bone quality is an important factor in implant mechanical stability following total knee arthroplasty. Quantitative computed tomography (CT) osteodensitometry has been used to measure the change in bone density post-operatively. We sought to validate the inter-observer reliability of these measurements. Sixteen CT scans were obtained on cadaveric lower limbs. Two observers independently obtained cortical and cancellous bone mineral density measurements from these scans. Eight CT scans were performed with prosthesis in situ and eight without. Results were compared using correlation coefficient and Bland–Altman analysis. The study showed a high correlation coefficient of greater than 0.990 for all slices. The mean difference between observers falls within two standard deviations of the mean as seen on a Bland–Altman plot. Quantitative CT-osteodensitometry is a reproducible method to measure bone mineral density changes about the knee and shows little variation between observers.

Background Bohler's angle and the crucial angle of Gissane can be used to assess calcaneal fractures. While the normal adult values of these angles are widely known, the normal paediatric values have not yet been established. Our aim is to investigate Bohler's angle and the crucial angle of Gissane in a paediatric population and establish normal paediatric reference values. Method We measured Bohler's angle and the crucial angle of Gissane using normal plain ankle radiographs of 763 patients from birth to 14 years of age completed over a five year period from July 2003 to June 2008. Results In our paediatric study group, the mean Bohler's angle was 35.2 degrees and the mean crucial angle of Gissane was 111.3 degrees. In an adult comparison group, the mean Bohler's angle was 39.2 degrees and the mean crucial angle of Gissane was 113.8 degrees. The differences in Bohler's angle and the crucial angle of Gissane between these two groups were statistically significant. Conclusion We have presented the normal values of Bohler's angle and the crucial angle of Gissane in a paediatric population. These values may provide a useful comparison to assist with the management of the paediatric calcaneal fracture.

Background: Current trends in the treatment of idiopathic clubfoot have shifted from extensive surgical release to more conservative techniques. The purpose of the present study was to prospectively compare the results of the Ponseti method with those of surgical releases for the correction of clubfoot deformity. Methods: We prospectively compared patients who had idiopathic clubfoot deformities that were treated at a single institution either with the Ponseti method or with below-the-knee casting followed by surgical release. The clinical records of the patients with a minimum duration of follow-up of two years were reviewed. All scheduled and completed operative interventions and associated complications were recorded. Results: Fifty-five patients with eighty-six clubfeet were treated; forty feet were included in the group that was treated with the Ponseti method, and forty-six feet were included in the group that was treated with below-the-knee casts followed by surgery (with three of these feet requiring casting only). There was no difference between the groups in terms of sex, ethnicity, age at the time of first casting, pretreatment Pirani score (average, 5.2 in both groups), or family history. The average number of casts was six in the Ponseti group and thirteen in the surgical group. Of the feet that were treated with below-the-knee casts, forty-three underwent surgery, with forty-two undergoing major surgery (posterior release [eleven] or posteromedial release [thirty-one]). In the Ponseti group, fourteen feet required fifteen operative interventions for recurrences, with only one foot requiring revision surgery. Four of these fifteen were major (necessitating posterior [one] or posteromedial release [three]) while eleven were minor. Thirteen feet in the surgical group required fourteen surgical revisions. Two postoperative complications were seen in each group. Conclusions: While both cohorts had a relatively high recurrence rate, the Ponseti cohort was managed with significantly less operative intervention and required less revision surgery. The Ponseti method has now been adopted as the primary treatment for clubfoot at our institution. Level of Evidence: Therapeutic Level II. See Instructions to Authors for a complete description of levels of evidence.

Relatively little is known about the functional anatomy of the lymphatic vessels draining the skin. To address this issue, we previously created a three-dimensional computer model of skin lymphatic drainage, using melanoma lymphoscintigraphy (LS) data from 5232 patients. In this study we sought to extend our model by performing a detailed statistical analysis of the mapped LS data to characterize the functional anatomy of the superficial lymphatics without any a-priori spatial bias. We investigated the commonly held assumption that lymphatic drainage is symmetric between the two sides of the body. Results indicated that, with the exception of the lower anterior torso, posterior leg and a small section of the posterior torso, most skin regions with sufficient data showed symmetric drainage. LS data from each symmetric skin region were then reflected to the opposite side of the body to provide an increased LS dataset for subsequent analysis. Cluster analysis was then applied to this reflected LS dataset to group regions of skin that drained in a similar manner. Results defined nine large clusters of skin, largely draining to the dominant axillary, groin, cervical level II and preauricular node fields. Each of the four axillary and groin node fields defined large clusters of skin on the torso, dividing it into regions similar to the historical 'Sappey's lines', although a fifth region of highly ambiguous drainage was also shown in the anterior and posterior center of the torso. Collectively, these results provide important new insights into skin lymphatic drainage, both improving and quantifying our understanding of functional lymphatic anatomy.

We measured bone density (BD) changes to assess adaptive bone remodelling five years after uncemented total hip arthroplasty with taper-design femoral component using quantitative computed-tomography-assisted osteodensitometry (qCT). Nineteen consecutive patients (21 hips) with degenerative joint disease were enrolled in the study. A press-fit cup and a tapered uncemented stem ceramic−ceramic pairing were used in all patients. Serial clinical, radiological and qCT osteodensitometry assessments were performed after the index operation and at the one, two and five year follow-ups. At the latest follow-up, the clinical outcome was rated satisfactory in all hips. The radiological assessment showed signs of osteointegration with stable fixation of all cups and stems. Overall, there was evidence of a BD loss at year five (p = 0.004). We estimate that BD loss was between 2.2% and 12.1% in comparison with baseline postoperative values. Progressive loss of BD in the metaphyseal region was observed in all hips. We found unremarkable BD changes of diaphyseal cortical BD throughout the five year follow-up period. qCT osteodensitometry technology allows differentiation of cortical and cancellous BD changes over time. Periprosthetic BD changes at the five year follow-up are suggestive of stable stem osteointegration with proximal femoral diaphysis load transfer and metaphyseal stress shielding.

The aim of this prospective study was to measure bone density changes and to assess adaptive bone remodelling after uncemented total hip arthroplasty with a taper-design femoral component using quantitative computer-tomography-assisted osteodensitometry. This method is able to differentiate cortical and cancellous bone structures. Twenty-seven consecutive patients (29 hips) with degenerative joint disease were enrolled in the study. Serial clinical, radiological and CT-osteodensitometry assessments were performed after the index operation. At the 2-year follow-up, the clinical outcome was rated satisfactory in all hips. The radiological assessment showed signs of osteointegration and stable fixation of all cups and stems. We observed a −17% decrease of cortical bone density and −22% decrease of cancellous bone density in the greater trochanter and femoral neck region. Cortical and cancellous bone density decrease at the level of the lesser trochanter was −9% and respectively −4%. We observed small changes of cortical bone density in the diaphyseal regions; in contrast, cancellous bone density increased (range 6% to 27%) in the diaphyseal regions. Overall, a trend of bone density recovery was observed throughout the follow-up period. Periprosthetic bone density changes at the 2-year follow-up are suggestive of stable osteointegration with proximal femoral diaphysis load transfer and moderate metaphyseal stress-shielding.

The vital heart beat that pumps blood around the body is caused by millions of cardiac muscle cells exciting and contracting in concert. Cellular contraction is inextricably linked to the sarcoplasmic reticulum (SR) release event and subsequent binding of Ca2+ to myofibril binding sites. An integral protein in the release event is the SR membrane bound Ryanodine Receptor (RyR). Ca2+ enters the narrow spaces between transverse tubules and the termini of the SR via voltage-gated L-type Ca2+ channels. It then binds to RyR's to evoke the release of more Ca2+ from the SR, into the cytosol. Mathematical models examining this mechanism of excitation-contraction coupling (ECC) have thus far lacked anatomically realistic parameters for representing the ultrastructure and the distributions of key proteins in these myocytes. Our work has focused on producing an anatomically correct 3D model of a healthy cardiomyocyte that represents the spatial organization of the different cellular components involved in ECC. To this end, this study seeks to develop and perform statistical analyses on the 3D spatial distribution of RyR's and other ECC proteins in the healthy cell. Using immunofluorescence confocal microscopy images of rat ventricular muscle, we have carried out 3D spatial analyses which have enabled us to investigate the anisotropy, clustering, randomness and scatter of RyR's. We have also examined aspects of the spatial relationship between RyR's and myofibrils at Z-disks via the implementation of computational models. We have thus developed a novel anatomically based model of cardiomyocyte RyR distribution. This combined with models of other ECC component proteins, will enable us to gain new insights into the role of cardiomyocyte ultrastructure in determining the spatiotemporal changes in intracellular Ca2+ which is central in ECC.

Diabetic cardiomyopathy is characterized by reduced cardiac output and is linked to subcellular level changes in cell structure and function. Although a number of studies have quantified the effect on protein distribution, Ca2+ handling and kinetics, the alterations in spatial organization of the major cell organelles have not been fully quantified before. We therefore studied organelle distribution in detail to study the effect of changes on, for example, calcium dynamics in an integrated manner. Cells from healthy and diabetic (following injection of STZ) Wistar rats were imaged under a transmission electron microscope. The spatial distribution of the mitochondria and myofibrils were analyzed in these images to determine a statistical model (using spatial statistics theory) that would adequately represent their characteristic distribution in cells from healthy versus diabetic animals. The model was calibrated using control and diabetic animal data such as shown in Fig. 1. This also allowed us to statistically quantify the differences in spatial organization. We present these structural differences and assess the influence of these changes on the spatial and temporal dynamics of cytosolic calcium during calcium-induced calcium release in an integrated 3D computational model.View Large Image | View Hi-Res Image | Download PowerPoint Slide

Mitochondria are recognized as dynamic organelles, which constantly undergo morphological remodeling through fusion and fission processes. However, their geometric details including individual shape, size, and spatial distribution have not been quantitatively characterized in adult cardiomyocytes. Standard optical microscopy is unable to resolve neighboring mitochondria, which are intensely packed between myofilament bundles and narrow sub-sarcolemmal space. On the other hand, 3D reconstructs generated by serial thin-section transmission electron microscopy (EM) or EM tomography can only provide a limited field of view. We applied a novel advanced 3D electron microscopic technology, serial block-face scanning electron microscopy (SBFSEM), to adult mouse ventricular tissues, segmented mitochondria, and created geometric models of mitochondrial assembly. Substantially large volumes enclosing neighboring myocytes were imaged using SBFSEM. Subsequently, we applied spatial analysis tools using Spatstat R package to quantify organization of mitochondria. In cross-sectional slices generated from SBFSEM volumes, the boundaries of individual mitochondria were extracted and the centroid of each boundary was plotted. Analysis of the distribution of these centroids using a quadrat test of the intensity plot indicated borderline inhomogenity (p=0.053). The test was rerun after redrawing quadrats, now incorporating the location of the nucleus in the 3D stack. The results confirmed that mitochondria were clustered near the nucleus (p=0.017). The cell-wide inter-point interaction between mitochondrial centroids calculated by the L-function and the pair correlation function failed to support organized mitochondrial clustering. In summary, the study revealed the strength of the new integrated use of SBFSEM imaging and computational statistics to characterize and parameterize the spatial distribution of cellular organelles such as mitochondria that are dynamically remodeled under a physiological condition and more intensely in disease settings such as diabetic cardiomyopathy and heart failure.

Background Acute indicators of response to cardiac resynchronisation therapy (CRT) are critical for developing lead optimisation algorithms and evaluating novel multi-polar, multi-lead and endocardial pacing protocols. Accounting for beat-to-beat variability in measures of acute haemodynamic response (AHR) may help clinicians understand the link between acute measurements of cardiac function and long term clinical outcome. Methods and results A retrospective study of invasive pressure tracings from 38 patients receiving an acute pacing and electrophysiological study was performed. 602 pacing protocols for left ventricle (LV) (n = 38), atria–ventricle (AV) (n = 9), ventricle–ventricle (VV) (n = 12) and endocardial (ENDO) (n = 8) optimisation were performed. AHR was measured as the maximal rate of LV pressure development (dP/dtMx) for each beat. The range of the 95% confidence interval (CI) of mean AHR was ~ 7% across all optimisation protocols compared with the reported CRT response cut off value of 10%. A single clear optimal protocol was identifiable in 61%, 22%, 25% and 50% for LV, AV, VV and ENDO optimisation cases, respectively. A level of service (LOS) optimisation that aimed to maximise the expected AHR 5th percentile, minimising variability and maximising AHR, led to distinct optimal protocols from conventional mean AHR optimisation in 34%, 78%, 67% and 12.5% of LV, AV, VV and ENDO optimisation cases, respectively. Conclusion The beat-to-beat variation in AHR is significant in the context of CRT cut off values. A LOS optimisation offers a novel index to identify the optimal pacing site that accounts for both the mean and variation of the baseline measurement and pacing protocol.

We compared the microbiology of middle ear fluid (MEF) in two cohorts of children having ventilation tube (VT) insertion; the first in the era of 7-valent Streptococcus pneumoniae conjugate vaccine (PCV7) and the second following introduction of the ten-valent pneumococcal vaccine (PHiD-CV10). Methods During 2011 (Phase 1) and again in 2014 (Phase 2) MEF and NP samples from 325 children and 319 children were taken at the time of VT insertion. A matched comparison group had NP swabs collected with 137 children (Phase 1) and 154 (Phase 2). Culture was performed on all NP and MEF samples with further molecular identification of Haemophilus species, serotyping of S. pneumoniae , and polymerase chain reaction (PCR) testing on all MEF samples. Results In Phase 2 immunisation coverage with ⩾3 doses of PHiD-CV10 was 93%. The rate and ratios of culture and molecular detection of the 3 main otopathogens was unchanged between Phase 1 and Phase 2 in both MEF and NP. Haemophilus influenzae was cultured in one quarter and detected by PCR in 53% of MEF samples in both time periods. S. pneumoniae and Moraxella catarrhalis were cultured in up to 13% and detected by PCR in 27% and 40% respectively of MEF samples . H. influenzae was the most common organism isolated from NP samples (61%) in the children undergoing VT surgery whilst M. catarrhalis (49%) was the most common in the non-otitis prone group. 19A was the most prominent S. pneumoniae serotype in both MEF and NP samples in Phase 2. Of Haemophilus isolates, 95% were confirmed to be non-typeable H. influenzae (NTHi) over both time periods . Conclusion Following implementation of PHiD-CV10 in New Zealand, there has been no significant change in the 3 major otopathogens in NP or MEF in children with established ear disease. For these children non-typeable H. influenzae remains the dominant otopathogen detected.

Spatio-temporal dynamics of intracellular calcium, [Ca2+]i, regulate the contractile function of cardiac muscle cells. Measuring [Ca2+]i flux is central to the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease. However, current imaging techniques are limited in the spatial resolution to which changes in [Ca2+]i can be detected. Using spatial point process statistics techniques we developed a novel method to simulate the spatial distribution of RyR clusters, which act as the major mediators of contractile Ca2+ release, upon a physiologically-realistic cellular landscape composed of tightly-packed mitochondria and myofibrils. We applied this method to computationally combine confocal-scale (~ 200 nm) data of RyR clusters with 3D electron microscopy data (~ 30 nm) of myofibrils and mitochondria, both collected from adult rat left ventricular myocytes. Using this hybrid-scale spatial model, we simulated reaction-diffusion of [Ca2+]i during the rising phase of the transient (first 30 ms after initiation). At 30 ms, the average peak of the simulated [Ca2+]i transient and of the simulated fluorescence intensity signal, F/F0, reached values similar to that found in the literature ([Ca2+]i ≈1 μM; F/F0≈5.5). However, our model predicted the variation in [Ca2+]i to be between 0.3 and 12.7 μM (~3 to 100 fold from resting value of 0.1 μM) and the corresponding F/F0 signal ranging from 3 to 9.5. We demonstrate in this study that: (i) heterogeneities in the [Ca2+]i transient are due not only to heterogeneous distribution and clustering of mitochondria; (ii) but also to heterogeneous local densities of RyR clusters. Further, we show that: (iii) these structure-induced heterogeneities in [Ca2+]i can appear in line scan data. Finally, using our unique method for generating RyR cluster distributions, we demonstrate the robustness in the [Ca2+]i transient to differences in RyR cluster distributions measured between rat and human cardiomyocytes., Author Summary Calcium (Ca2+) acts as a signal for many functions in the heart cell, from its primary role in triggering contractions during the heartbeat to acting as a signal for cell growth. Cellular function is tightly coupled to its ultra-structural organization. Spatially-realistic and biophysics-based computational models can provide quantitative insights into structure-function relationships in Ca2+ signaling. We developed a novel computational model of a rat ventricular myocyte that integrates structural information from confocal and electron microscopy datasets that were independently acquired and includes: myofibrils (protein complexes that contract during the heartbeat), mitochondria (organelles that provide energy for contraction), and ryanodine receptors (RyR, ion channels that release the Ca2+ required to trigger myofibril contraction from intracellular stores). Using this model, we examined [Ca2+]i dynamics throughout the cell cross-section at a much higher resolution than previously possible. We estimated the size of structural maladaptation that would cause disease-related alterations in [Ca2+]i dynamics. Using our methods for data integration, we also tested whether reducing the density of RyRs in human cardiomyocytes (~40% relative to rat) would have a significant effect on [Ca2+]i. We found that Ca2+ release patterns between the two species are similar, suggesting Ca2+ dynamics are robust to variations in cell ultrastructure.