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Supplemental Digital Content is available in the text., Severe acute respiratory distress syndrome (ARDS) unresponsive to conventional intensive care unit (ICU) management is an accepted indication for venovenous extracorporeal membrane oxygenation (V-V ECMO) support. The frequency with which patients with coronavirus disease 2019 (COVID-19) pneumonia are selected for V-V ECMO has not been described. This was a cohort study including all patients placed on either V-V ECMO or venoarteriovenous ECMO at the four adult ECMO Centers of Excellence. Primary outcomes evaluated were survival to decannulation from the ECMO circuit, survival to discharge, and 60-day survival. Secondary outcomes were hospital length of stay (LOS), ICU LOS, length of ECMO cannulation, and length of intubation. During the study period, which corresponded to the first surge in COVID-19 hospitalizations in Minnesota, 35 patients with ARDS were selected for V-V ECMO support out of 1,849 adult ICU patients with COVID-19 infection in the state (1.9% incidence; 95% CI, 1.3–2.6%). This represents 46 (95% CI, 34–61) expected V-V ECMO patients per 100,000 confirmed positive cases of COVID-19. Twenty-six of the 35 patients (74.3%) supported with V-V ECMO survived to 60-day post-ECMO decannulation. Recent studies have demonstrated ongoing success rescuing patients with severe ARDS in COVID-19 infection. Our data add to the support of ECMO and the consideration for encouraging cooperation among regional ECMO centers to ensure access to this highest level of care. Finally, by evaluating all the patients of a single region, we estimate overall need for this resource intensive intervention based on the overall number of COVID-19 cases and ICU admissions.

Background: Venovenous extracorporeal membrane oxygenation (VV-ECMO) for select adults with severe acute respiratory distress syndrome (ARDS) cause by coronavirus disease 2019 (COVID-19) infection is a guideline-supported therapy with associated hospital survival of 62%-74%, similar to expected survival with VV-ECMO for other indications. However, ECMO is a resource-heavy intervention, and these patients often require long ECMO runs and prolonged intensive care unit (ICU) care. Identifying factors associated with mortality in VV-ECMO patients with COVID-19 infection can inform the evaluation of ECMO candidates as well as prognostication for those patients on prolonged VV-ECMO. Patients and Methods: This was a retrospective cohort study that included all patients who received either VV- or venoarteriovenous (VAV)-ECMO at one of four ECMO Centers of Excellence in the state of Minnesota between March 1, 2020 and November 1, 2020. The primary outcome was 60-day survival. Secondary outcomes were hospital complications, infectious complications, and complications from ECMO. Results: There were 46 patients who met criteria during this study period and 30 survived to 60-day follow-up (65.2%). Prior to cannulation, older patient age (55.5 in non-survivors vs. 49.1 years in survivors; p = 0.03), lower P/F ratio (62.1 vs. 76.2; p = 0.04), and higher sequential organ failure assessment (SOFA) score (8.1 vs. 6.6; p = 0.02) were identified as risk factors for mortality. After ECMO cannulation, increased mortality was associated with increased number of antibiotic days (25.9 vs. 14.5; p = 0.04), increased number of transfusions (23.9 vs. 9.9; p = 0.03), elevated white blood cell (WBC) count at post-ECMO days one through three, elevated D-dimer at post-ECMO day 21-27, and decreased platelet count from post-ECMO days 14 and onward using univariable analysis. Conclusions: Multiple markers of infection including leukocytosis, thrombocytopenia, and increased antibiotic days are associated with increased mortality in patients placed on VV-ECMO for COVID-19 infection and subsequent ARDS. Knowledge of these factors may assist with determining appropriate candidates for this limited resource as well as direct goals of care in prolonged ECMO courses.

The presence of T regulatory cells (Tregs) is highly required in normal skin in order to maintain immune tolerance to commensal microbes and to prevent the development of immune-mediated inflammation. Psoriasis is a chronic inflammatory skin disease in which effector T cells, namely, Th17 and their relevant pro-inflammatory cytokines are increased in peripheral blood as well as in the inflamed skin. The status of Tregs in psoriatic skin is continuously studied. In this case, CD4 + CD25high T cells and other regulatory cytokines such as IL-35 are demonstrated to be significantly decreased. Aiming to better characterize Tregs in psoriatic skin and to establish the finding of their abnormal balance, we assessed the expression of semaphorin3A and neuropilin-1 (both reported as biomarkers of Tregs). Semaphorin3A and neuropilin-1 expressing Tregs were found to be significantly decreased in psoriatic skin when compared to normal skin. These findings were supported by demonstrating the downregulation of IL-10 expression in psoriatic skin. Our findings suggest that semaphoring3A may turn to be a new promising therapeutic approach in the process of improving Treg function in psoriasis.

Patients undergoing total knee arthroplasty often have unfulfilled expectations from the surgery that can lead to dissatisfaction. This study aimed to examine the discrepancy between patients’ expectations and actual functional abilities prior to undergoing knee replacement surgery, and at 6 and 12 months following the surgery. A survey was undertaken of patients before, and 6 and 12 months post-surgery. The survey included the Knee Surgery Perception Questionnaire (KSPQ) to assess patients’ current perception of their level of function and pain, their desired outcomes, and the discrepancy between the two. Pain, function and quality of life were also assessed. Repeated measure ANOVAs were used to assess differences between pre- and post-surgery. A total of 176 patients were surveyed. Significant differences in the KSPQ discrepancy scores (subscale and total scores) were demonstrated between the three assessment point times (p

In the most severe cases, novel coronavirus (SARS-CoV-2) infection leads to Acute Respiratory Distress Syndrome which may be refractory to standard medical interventions including mechanical ventilation. There are growing reports of the use of venovenous (VV) extracorporeal membrane oxygenation (ECMO) in these cases. A subset of critically ill COVID-19 patients develops cardiomyopathy as well, manifested by cardiogenic shock with reduced ejection fraction, dysrhythmias, and subsequent increase in mortality. One strategy for managing ARDS with an element of cardiogenic shock is venoarteriovenous (VAV) ECMO. Less than 1% of the cases in the worldwide ELSO COVID-19 database employed any form of hybrid cannulation. To date, there has only been one reported case of patient salvage with arterial or partial arterial support. We present a case that demonstrates the potential role of VAV ECMO in the case of concomitant severe ARDS with cardiomyopathy in the setting of COVID-19 infection.

The advent of immune checkpoint therapy for metastatic skin cancer has greatly improved patient survival. However, most skin cancer patients are refractory to checkpoint therapy, and furthermore the differential intra-immune signaling between cancers driving the response to checkpoint therapy remains uncharacterized. When comparing the immune transcriptome in the tumor microenvironment of melanoma and basal cell carcinoma (BCC), we found that the presence of memory B cells and macrophages negatively correlate when stratifying patients by response, with memory B cells more present in responders. Inhibitory immune signaling is reduced in melanoma responders and is increased in BCC responders. We further explored the relationships between macrophages, B cells and response to checkpoint therapy by developing a stochastic differential equation model which qualitatively agrees with the data analysis. Our model predicts BCC to be more refractory to checkpoint therapy than melanoma. We show differences in tumor progression and regression that could serve as a diagnostic and predict the optimal ratio of macrophages and memory B cells for successful treatment.

Introduction: Venovenous extracorporeal membrane oxygenation (V-V ECMO) improves survival in patients with ARDS from COVID-19 pneumonia. Due to equipment shortages throughout the pandemic, systems for allocation have been proposed, but not tested. In this study, we evaluate 3 systems of allocation for V-V ECMO in both pre-COVID-19 and COVID-19 patients with ARDS. Methods: We retrospectively evaluated 3 systems of ECMO allocation (MN, MDH, and OHI) across 4 ECMO Centers of Excellence. Logistic regression was used to assess the relationship between the scores and in-hospital and 30-day mortality. Cut points for priority groups were evaluated by maximizing the sum of sensitivity and specificity. Results: Of 124 patients, 38% were treated for COVID-19 ARDS. The median age was 48 years and 73% were male. The in-hospital mortality rate was 38% and increased to 42% at 30 days. For each additional point in the MN score, the odds ratio for mortality was 1.13 (p = 0.02) for in-hospital and 1.15 (p = 0.015) at 30 days. OHI and MDH scores were not significant for in-hospital or 30-day mortality. COVID-19 status did not change the findings significantly. For the MN score, a threshold between the low and medium priority groups was found to be 7 and the threshold between medium and high priority groups was found to be 9 (p = 0.05) (Fig. 1). Conclusions: Higher MN score is associated with increased mortality. Proposed priority groups can be used to identify patients that would more greatly benefit from V-V ECMO allocation in times of increasing scarcity. [Formula presented]

The purpose is to discuss and exemplify how a typological approach could be designed for studying phenomena believed to be best understood within a person-oriented theoretical framework. The focus is mainly restricted to the case of studying the typological structure of a sample at a single point in time, and restricted to analyzing variable profiles where each variable has a “negative” and “positive” endpoint. An artificial data set and an empirical data set were analyzed using two different methodological approaches, one more explorative (using LICUR, a cluster analysis-based procedure) and one more model-based (using the MCLUST procedure). For the artificial data set, the LICUR procedure was successful in finding the true classification structure but the MCLUST procedure performed surprisingly badly. For the empirical data set, both procedures produced rather similar solutions and they showed moderate validity. However, the LICUR solution appeared to be slightly superior. It was argued that applying a sound classification methodology and carefully validating the resulting classifications are extremely important, even more so in a developmental context. It was also argued that, in a number of situations, a more explorative approach could be more useful than a standard model-based one.

Background Total hip/total knee replacement (THR/TKR) surgery is becoming an increasingly common approach for the management of primarily lower limb osteoarthritis. A number of factors such as reducing mobility, structural joint changes, and pain may predispose those awaiting hip and knee surgery to falls, which may impact on pre- and postsurgery functions. The aim of this study was to identify the prevalence of falls in the year preceding THR/TKR surgery, and factors associated with falls. Methods Cross-sectional survey of patients scheduled for THR/TKR, including measures of joint disease severity, falls, falls efficacy, quality of life, pain, and depression. Comparisons across falls status (nonfaller, single faller, or multiple faller) and high/low disease severity for both THR and TKR groups were undertaken. Results A total of 282 people (mean age 67.3 years) completed surveys before the surgery (197 TKR). As much as 41% reported one or more falls in the preceding year, and participants reported that the affected joint contributed to the fall in 35% of the cases. TKR multiple fallers (≥ 2 falls) had significantly lower falls efficacy, worse function, greater pain catastrophizing and depression, and poorer 36-Item Short Form Survey Mental Component Scores than nonmultiple fallers. For both THR and TKR groups, several measures were significantly worse for those with greater disease severity, including falls efficacy, depression, pain catastrophizing, self-rated health, and physical activity. Conclusion Falls are common in the 12 months preceding total hip or knee surgery. A number of factors are associated with risk of multiple falls and with joint disease severity. Strategies to reduce falls risk should be a priority in the year preceding lower limb joint surgery to optimize presurgery and postsurgery outcomes.

We present an upper limit on the flux of ultra-high-energy down-going neutrinos for $E > 10^{18}\ \mbox{eV}$ derived with the nine years of data collected by the Telescope Array surface detector (05-11-2008 -- 05-10-2017). The method is based on the multivariate analysis technique, so-called Boosted Decision Trees (BDT). Proton-neutrino classifier is built upon 16 observables related to both the properties of the shower front and the lateral distribution function., 10 pages, 4 figures, accepted to JETP

Simple Summary Despite the successes of immune checkpoint therapy in treating metastatic skin cancers, most patients either fail to respond or become unresponsive to immunotherapy. We found that the cell–cell communication of two different immune cell types, macrophages and memory B cells, correlate very strongly with the response to immunotherapy. We built a mathematical model based on these results that predict different skin cancers would have different response rates and predict that a high ratio of memory B cells to macrophages is optimal for a response to immunotherapy. Abstract The advent of immune checkpoint therapy for metastatic skin cancer has greatly improved patient survival. However, most skin cancer patients are refractory to checkpoint therapy, and furthermore, the intra-immune cell signaling driving response to checkpoint therapy remains uncharacterized. When comparing the immune transcriptome in the tumor microenvironment of melanoma and basal cell carcinoma (BCC), we found that the presence of memory B cells and macrophages negatively correlate in both cancers when stratifying patients by their response, with memory B cells more present in responders. Moreover, inhibitory immune signaling mostly decreases in melanoma responders and increases in BCC responders. We further explored the relationships between macrophages, B cells and response to checkpoint therapy by developing a stochastic differential equation model which qualitatively agrees with the data analysis. Our model predicts BCC to be more refractory to checkpoint therapy than melanoma and predicts the best qualitative ratio of memory B cells and macrophages for successful treatment.

Objective To test the hypothesis that gene expression profiling in peripheral blood from patients who have undergone kidney transplantation (KT) will provide mechanistic insights regarding graft repair and regeneration. Background Renal grafts obtained from living donors (LD) typically function immediately, whereas organs from donation after cardiac death (DCD) or acute kidney injury (AKI) donors may experience delayed function with eventual recovery. Thus, recipients of LD, DCD, and AKI kidneys were studied to provide a more complete understanding of the molecular basis for renal recovery. Methods Peripheral blood was collected from LD and DCD/AKI recipients before transplant and throughout the first 30 days thereafter. Total RNA was isolated and assayed on whole genome microarrays. Results Comparison of longitudinal gene expression between LD and AKI/DCD revealed 2 clusters, representing 141 differentially expressed transcripts. A subset of 11 transcripts was found to be differentially expressed in AKI/DCD versus LD. In all recipients, the most robust gene expression changes were observed in the first day after transplantation. After day 1, gene expression profiles differed depending upon the source of the graft. In patients receiving LD grafts, the expression of most genes did not remain markedly elevated beyond the first day post-KT. In the AKI/DCD groups, elevations in gene expression were maintained for at least 5 days post-KT. In all recipients, the pattern of coordinate gene overexpression subsided by 28 to 30 days. Conclusions Gene expression in peripheral blood of AKI/DCD recipients offers a novel platform to understand the potential mechanisms and timing of kidney repair and regeneration after transplantation.

Wounds to the head, neck, and extremities have been estimated to account for ∼84% of reported combat injuries to military personnel. Volumetric muscle loss (VML), defined as skeletal muscle injuries in which tissue loss results in permanent functional impairment, is common among these injuries. The present standard of care entails the use of muscle flap transfers, which suffer from the need for additional surgery when using autografts or the risk of rejection when cadaveric grafts are used. Tissue engineering (TE) strategies for skeletal muscle repair have been investigated as a means to overcome current therapeutic limitations. In that regard, human hair-derived keratin (KN) biomaterials have been found to possess several favorable properties for use in TE applications and, as such, are a viable candidate for use in skeletal muscle repair. Herein, KN hydrogels with and without the addition of skeletal muscle progenitor cells (MPCs) and/or insulin-like growth factor 1 (IGF-1) and/or basic fibroblast growth factor (bFGF) were implanted in an established murine model of surgically induced VML injury to the latissimus dorsi (LD) muscle. Control treatments included surgery with no repair (NR) as well as implantation of bladder acellular matrix (BAM). In vitro muscle contraction force was evaluated at two months postsurgery through electrical stimulation of the explanted LD in an organ bath. Functional data indicated that implantation of KN+bFGF+IGF-1 (n = 8) enabled a greater recovery of contractile force than KN+bFGF (n = 8)***, KN+MPC (n = 8)**, KN+MPC+bFGF+IGF-1 (n = 8)**, BAM (n = 8)*, KN+IGF-1 (n = 8)*, KN+MPCs+bFGF (n = 9)*, or NR (n = 9)**, (*p

A short overview of the person-oriented approach is given as a guide to the researcher interested in carrying out person-oriented research. Theoretical, methodological, and practical considerations of the approach are discussed. First, some historical roots are traced, followed by a description of the holisticinteractionistic research paradigm, which provided the general framework for the development of the modern person-oriented approach. The approach has both a theoretical and a methodological facet and after presenting its key theoretical tenets, an overview is given of some common person-oriented methods. Central to the person-oriented approach is a system view with its components together forming a pattern regarded as indivisible. This pattern should be understood and studied as a whole, not broken up into pieces (variables) that are studied as separate entities. Hence, usually methodological tools are used by which whole patterns are analysed (e.g. cluster analysis). An empirical example is given where the pattern development of school grades is studied.

Pain and disability often persist following hip (THR) and knee replacement (TKR) surgery predisposing patients to increased risk of falling. This study identified pre-operative predictors for post-operative falls in TKR and THR patients, and the incidence and circumstances of falls in the 12 months post-surgery. A survey was undertaken of patients before THR and TKR, and was repeated 12 months post-operation. The survey included (1) medical history and medications usage, (2) pain and function, (3) health-related and physical activity and (4) fear of falls and history of falls questionnaires. Patients were classified as ‘fallers’ (≥1 fall) or ‘non-fallers’ based on prospectively documented falls in the 12 months post-surgery. Binary logistic regression was conducted to identify independent pre-operative predictors of incident falls status. Eighty-two of the 243 participants (33.7%) reported ≥1 fall in the 12 months post-operatively [60 (34.1%) patients following TKR and 22 (32.8%) following THR]. The logistic regression model was statistically significant, χ 2 = 24.731, p

Background The combined effects of balanced transfusion ratios and use of procoagulant and antifibrinolytic therapies on trauma-induced exsanguination are not known. The aim of this study was to investigate the combined effect of transfusion ratios, tranexamic acid and products containing fibrinogen on the outcome of injured patients with bleeding. Methods A prospective multicentre observational study was performed in six level 1 trauma centres. Injured patients who received at least 4 units of red blood cells (RBCs) were analysed and divided into groups receiving a low (less than 1 : 1) or high (1 or more : 1) ratio of plasma or platelets to RBCs, and in receipt or not of tranexamic acid or fibrinogen products (fibrinogen concentrates or cryoprecipitate). Logistic regression models were used to assess the effect of transfusion strategies on the outcomes ‘alive and free from massive transfusion’ (at least 10 units of RBCs in 24 h) and early ‘normalization of coagulopathy’ (defined as an international normalized ratio of 1·2 or less). Results A total of 385 injured patients with ongoing bleeding were included in the study. Strategies that were independently associated with an increased number of patients alive and without massive transfusion were a high platelet to RBC ratio (odds ratio (OR) 2·67, 95 per cent c.i. 1·24 to 5·77; P = 0·012), a high plasma to RBC ratio (OR 2·07, 1·03 to 4·13; P = 0·040) and treatment with tranexamic acid (OR 2·71, 1·29 to 5·71; P = 0·009). No strategies were associated with correction of coagulopathy. Conclusion A high platelet or plasma to RBC ratio, and use of tranexamic acid were associated with a decreased need for massive transfusion and increased survival in injured patients with bleeding. Early normalization of coagulopathy was not seen for any transfusion ratio, or for use of tranexamic acid or fibrinogen products.

Objectives. Foot orthoses are commonly used in the management of knee OA, although the relationship between foot function and knee OA is still unclear. The purpose of the study was to examine foot function during walking in people with and without medial compartment knee OA. Methods. Motion of the tibia, rearfoot and forefoot in 32 patients with medial compartment knee OA and 28 age-matched control subjects was investigated. Multivariate analysis was used to compare the groups. Results. The knee OA group contacted the ground with a more everted rearfoot, demonstrated greater peak rearfoot eversion and exhibited reduced rearfoot frontal plane range of motion and reduced rearfoot peak inversion. The tibia was more internally rotated and laterally tilted throughout the gait cycle, with reduced peak external rotation. Conclusion. People with medial compartment knee OA exhibit altered foot kinematics during gait that are indicative of a less mobile, more everted foot type. The presence and degree of tibial malalignment and the available rearfoot range of motion during walking may affect individual responses to load-altering interventions, such as foot orthoses and footwear modifications. Trial registration: Australian New Zealand Clinical Trials Registry, www.anzctr.org.au/, ACTRN

The differences in crime scene actions in cases of stranger rape committed by convicted offenders were examined between 31 single-victim rapists and 35 serial rapists. Data were collected from police files, court verdicts, psychiatric evaluations, and criminal records. Findings indicate that the serial rapists were more criminally sophisticated than the single-victim rapists, during their first and second rapes. The single-victim rapists were significantly more likely to engage in the interpersonal involvement behavior of kissing the victim, and to engage in pre-assault alcohol use, than the serial rapists. There was, however, no significant difference in physically violent or sexual behaviors. To investigate the possibility of predicting rapist type, logistic regression analyses were performed. Results indicate that three behaviors in conjunction, kissed victim, controlled victim, and offender drank alcohol before the offense, predicted whether an unknown offender is a single-victim or serial rapist with a classification accuracy of 80.4%. The findings have implications for the classification of stranger rapists in offender profiling.

The purpose of this study was to compare the electromyographic (EMG) amplitudes of the quadriceps femoris (QF) muscles during a maximum voluntary isometric contraction (MVIC) to submaximal and maximal dynamic concentric contractions during active exercises. A secondary purpose was to provide information about the type of contraction that may be most appropriate for normalization of EMG data if one wants to determine if a lower extremity closed chain exercise is of sufficient intensity to produce a strengthening response for the QF muscles. Sixty-eight young healthy volunteers (39 female, 29 male) with no lower extremity pain or injury participated in the study. Surface electrodes recorded EMG amplitudes from the vastus medialis obliquus (VMO), rectus femoris (RF), and vastus lateralis (VL) muscles during 5 different isometric and dynamic concentric exercises. The last 27 subjects performed an additional 4 exercises from which a second data set could be analyzed. Maximum isokinetic knee extension and moderate to maximum closed chain exercises activated the QF significantly more than a MVIC. A 40-cm. lateral step-up exercise produced EMG amplitudes of the QF muscles of similar magnitude as the maximum isokinetic knee extension exercises and would be an exercise that could be considered for strengthening the QF muscles. Most published EMG studies of exercises for the QF have been performed by comparing EMG amplitudes during dynamic exercises to a MVIC. This procedure can lead one to overestimate the value of a dynamic exercise for strengthening the QF muscles. We suggest that when studying the efficacy of a dynamic closed chain exercise for strengthening the QF muscles, the exercise be normalized to a dynamic maximum muscle contraction such as that obtained with knee extension during isokinetic testing.

Objective Knee osteoarthritis (OA) has been shown to be a risk factor for falls. Reductions in foot clearance during the swing phase of walking can cause a trip and potentially lead to a fall. This study examined the swing phase mechanics of people with and without knee OA during walking. Design Minimum toe clearance (MTC) height, joint angles at the time of MTC and the influence of the angular changes of the hip, knee and ankle of the swing leg on foot clearance using sensitivity analysis were investigated in 50 knee OA participants and 28 age-matched asymptomatic controls. Results Although both groups had a similar MTC height (controls: 12.8 ± 6.7 mm, knee OA: 13.4 ± 7.0 mm), the knee OA group used a different strategy to achieve the same foot clearance, as evidenced by greater knee flexion (52.5 ± 5.3° vs 49.4 ± 4.8°, p = 0.007), greater hip abduction (−3.6 ± 3.3° vs −1.8 ± 3.3°, p = 0.03) and less ankle adduction (2.8 ± 1.9° vs 4.2 ± 2.1°, p = 0.01). Conclusion MTC height was comparable between the groups, however a different swing phase mechanism was used by the knee OA. Although adequate MTC is an important component of safe locomotion, it does not appear to be impaired in people with knee OA. Other factors, such as inadequate responses to postural perturbation, may be responsible for falls in this group.

I-states-as-objects-analysis (ISOA) is a person-oriented methodology for studying short-term developmental stability and change in patterns of variable values. ISOA is based on longitudinal data with the same set of variables measured at all measurement occasions. A key concept is the i-state, defined as a person’s pattern of variable values at a specific time point. All i-states are first subjected to a classification analysis that results in a time-invariant classification characterized by a number of typical i-states. Each person is then characterized at each time point by the typical i-state he/she belongs to. Then the person’s sequences of typical i-states are analyzed with regard to structural and individual stability and change. Extensions of ISOA are presented where: (1) some methods for checking the assumption of a time-invariant classification are indicated; (2) information about the degree of dissimilarity between typical i-states is used as an aid in interpreting the findings; and (3) attention is given to closed paths—that is, typical i-state sequences that do not occur at all. To demonstrate the methods, an empirical example is given that concerns the development of children’s achievement-intelligence patterns between ages 10 and 13.

Human observers understand the content of an image intuitively. Based upon image content, they perform many image-related tasks, such as creating slide shows and photo albums, and organizing their image archives. For example, to select photos for an album, people assess image quality based upon the main objects in the image. They modify colors in an image based upon the color of important objects, such as sky, grass or skin. Serious photographers might modify each object separately. Photo applications, in contrast, use low-level descriptors to guide similar tasks. Typical descriptors, such as color histograms, noise level, JPEG artifacts and overall sharpness, can guide an imaging application and safeguard against blunders. However, there is a gap between the outcome of such operations and the same task performed by a person. We believe that the gap can be bridged by automatically understanding the content of the image. This paper presents algorithms for automatic tagging of perceptual objects in images, including sky, skin, and foliage, which constitutes an important step toward this goal.

Knee osteoarthritis (OA) is a major cause of disability and a risk factor for falls in older people. The purpose of this study was to assess the falls risk of people with knee OA before surgery and at 4 months following surgery and to compare this to a control group. Thirty-five patients with knee OA prior to undergoing knee replacement surgery and 27 asymptomatic age-matched controls participated in the study. The surgical group were tested prior to their surgery and at 4 months post-surgery. The short form of the Physiological Profile Assessment was used to assess falls risk and included tests of vision, lower limb proprioception, knee extension strength, reaction time and postural sway. Physical activity, quality of life, fear of falls and disability before and after surgery were also documented. At least one fall in the previous 12 months was reported for 48% of the surgical group compared with 30% of the control group. Following the surgery, there was a reduction in fear of falling and pain, and improvements in function for the surgical group. However, compared to the control group, the surgical group exhibited a greater fear of falling and reduced lower limb proprioception and knee extension strength both pre- and post-surgery. People who undergo knee replacement surgery may be at increased risk of falls both prior to and 4 months following their surgery, primarily due to deficits in knee extension strength and lower limb proprioception. Therefore, interventions to reduce the risk of falls should be implemented early after the surgery.

Background Inverse associations between IQ and stroke have been reported in a few studies, but none have investigated subtypes of stroke, nor have they studied fatal and non-fatal stroke separately. Stroke is a heterogenic disease and strength of associations with IQ and putative causal pathways cannot be assumed to be identical for different subtypes. Methods IQ was measured for 1.1 million Swedish men, born 1951 to 1976. Data from several national registers were linked and the cohort followed until the end of 2006 for non-fatal, and 2004 for fatal stroke. HRs with 95% CIs adjusted for age, body mass index, blood pressure and socioeconomic factors were estimated using Cox proportional hazards models. Results Inverse associations were found between IQ and all stroke subtypes. The strength of the associations differed by subtype, with the strongest RR found for haemorrhagic stroke. In adjusted models using IQ as a continuous variable over a standard nine point scale, HR for mortality in all stroke was 0.89 (95% CI 0.85 to 0.93), that is an 11% decrease in stroke risk per unit increase in IQ. For non-fatal stroke, the corresponding HR was 0.92 (95% CI 0.91 to 0.93). The results were based on a rather young cohort, and results should therefore be generalised to early stroke events rather than the general population. Conclusions Inverse associations were found between IQ and all stroke subtypes, fatal and non-fatal. For all types of non-fatal stroke, the inverse associations with IQ remained after adjustments for childhood and adult socioeconomic position.

This first issue of Journal for Person-Oriented Research is a special issue devoted to the presentation of person-oriented approaches taken by leading researchers in the area. A prototypic person-oriented approach has three characteristics: (1) A pattern focus, (2) A focus on the individual, and (3) A process focus. The approach includes a theoretical framework, based on the holistic-interactionistic research paradigm, and it usually implies using methods for studying individual development, particularly subject-specific methods, and methods for studying patterns of information as undivided “wholes”. Four papers in this special issue are theory-oriented, dealing with historical roots of the approach, implications of a person-oriented theory for the methodology applied in empirical research, and discussing conceptual issues, including definitions of terms and communalities and differences of a person-oriented approach to standard approaches. The next three articles concern the use of various forms of a multi-level approach that points to promising ways for further development of the person-oriented approach. In the penultimate article, a statistical package for person-oriented analysis (ROPstat) is introduced. In the last article, a dynamic systems approach is presented for studying adaptive equilibrium regulation that separates forces working at a short and a long timescale.

Summary Background The coexistence of mycosis fungoides, a peripheral T-cell lymphoma, and B-cell malignancies or Hodgkin's lymphoma in the same patient is unusual. Most descriptions are isolated case reports and case series are strikingly sparse. Objectives To detect cases of mycosis fungoides associated with B-cell malignancies or Hodgkin's lymphoma and to analyse the characteristics of and the interplay between the lymphoproliferative neoplasms. Method Patients with mycosis fungoides who had B-cell malignancies or Hodgkin's lymphoma were selected from among 398 patients either treated or followed up in two tertiary medical centres during a 7-year period. Results Eleven patients with mycosis fungoides and B-cell malignancy were detected (seven of non-Hodgkin's lymphoma, three of chronic lymphocytic leukaemia, one of multiple myeloma). No case of Hodgkin's lymphoma was found. In seven patients the mycosis fungoides preceded the B-cell malignancy whereas in four it was the B-cell malignancy which occurred first. The time elapsed between onset of the two malignancies ranged from 4 to 22 years (average: 12 years). Patients who had mycosis fungoides as the first neoplasm presented with earlier stages of mycosis fungoides (four of seven: IA, three of seven: IB) than those who had mycosis fungoides as their second neoplasm (of four, one: IB, one: folliculotropic, two: IIB). Among the four patients in whom the appearance of mycosis fungoides followed the B-cell malignancy, three had been treated with multiagent chemotherapy. Two patients who presented with early-stage mycosis fungoides (IA) as the first lymphoma developed mycosis fungoides tumours after becoming immunosuppressed. In two patients infiltrates composed of both malignant T- and B-cell populations were found in a single biopsy. One showed two distinct populations of the malignant cells in the skin tumour, thus constituting a classical composite lymphoma of mycosis fungoides and chronic lymphocytic leukaemia, while in the other patient the two malignant populations of marginal B-cell lymphoma and mycosis fungoides (as evidenced by both phenotypic and genotypic findings) were intermingled. Conclusions This case series indicates that while the coexistence of Hodgkin's lymphoma and mycosis fungoides is extremely rare, the association of mycosis fungoides and B-cell malignancies is not as rare as reflected in the literature, with non-Hodgkin's lymphoma constituting the most common associated B-cell malignancy. In this series as well as in the cases reported in the literature mycosis fungoides usually preceded the development of B-cell malignancies, which may be in accordance with previous reports of an increased risk of developing a second haematological neoplasm. The importance of a competent immune system for patients with mycosis fungoides is well demonstrated in these cases. It is suggested that for greater precision the criteria for diagnosis of composite lymphoma of the skin should include both phenotypic and genotypic features.

Background This study examines the relationship between functional capacity, left ventricular diastolic function, and myocardial perfusion reserve (MPR) in patients with left ventricular hypertrophy (LVH). Methods We studied 16 patients with LVH and 10 controls. Functional capacity was assessed by cardiopulmonary exercise, MPR by positron emission tomography, and left ventricular diastolic function by echo-Doppler. Results Functional capacity and MPR were significantly lower in the patients. Functional capacity correlated positively with MPR and left ventricular diastolic function. Conclusions Diminished functional capacity in patients with hypertension-induced LVH is related to the impairment in MPR and left ventricular diastolic function.

We examine the issue of distributed collaboration at the Jet Propulsion Laboratory (JPL). With the goals of “faster, better, cheaper” missions, an efficient, seamless collaboration capability is critical to future JPL space exploration missions. We assert that the current capabilities for distributed collaboration internal to JPL, as well as external, are unsatisfactory. This paper provides a vision of greatly enhanced distributed collaboration capabilities in the near future and into the far future. Our vision focuses primarily on distributed collaborative engineering and science. We believe enhanced capabilities are necessary in two collaborative paradigms: the virtual conference and the shared virtual workspace. We describe these collaborative paradigms, and discuss the tools that exist and the additional capability necessary to achieve the collaborative vision with respect to the types of data we typically work with at JPL. We identify the following types of data frequently exchanged in collaborative activities: project planning data, design data, notes/documentation, communication data, analysis/performance data, verification data and scientific data. Our analysis shows that at present there is good GroupWare support for project planning data and notes/documentation data. Support is improving for design data. Other data types have no or sporadic support at best.

Acute increases in blood pressure (BP) increase myocardial tumor necrosis factor (TNF)-alpha production, but it is not known whether chronic hypertensive stress elevates myocardial TNF-alpha production, possibly contributing to cardiac remodeling, decreased cardiac function, and faster progression to heart failure. BP, cardiac function, and size were evaluated in normotensive [Sprague-Dawley (SD)], spontaneously hypertensive (SHR), and spontaneously hypertensive heart failure-prone (SHHF) rats at 6, 12, 15, and 18 mo of age and in failing SHHF. Left ventricular tissues were evaluated for secretion of bioactive TNF-alpha and inhibition of TNF-alpha secretion by phosphodiesterase inhibitors. All ventricles secreted bioactive and immunoreactive TNF-alpha, but secretion decreased with age. SHR and SHHF rats secreted more TNF-alpha than SD rats at 6 mo of age, but only failing SHHF rats secreted significantly more TNF-alpha at 18 mo. Amrinone inhibited TNF-alpha secretion in all rats and was less potent but more efficacious than RO-201724 in all strains. TNF-alpha secretion correlated with BP and left ventricular mass in 6-mo-old rats, but this relationship disappeared with age. Results suggest that hypertension and/or cardiac remodeling is associated with elevated myocardial TNF-alpha, and, although hypertension, per se, did not maintain elevated cardiac TNF-alpha levels, SHHF rats increase TNF-alpha production during the end stages of failure.

Sequential design and multivariate analysis were adopted to search for an optimal and robust granulation and tabletting process for a melt granulation process. The advantage with this procedure should be to produce tablets directly from granules prepared in one step without addition of any solvents. First the granulation process was investigated by a 26−2 fractional factorial design with six center points. The most important variables were identified, e.g., binder, PEG and HPMC. The main objective of the whole study was to investigate the influence of granules with different properties on the quality of the final tablet. Thus, five granulation batches, that spanned the experimental domain well in the first study, were chosen to vary along with four tabletting variables by a 25−1 fractional factorial design with seven center points. The results show that the properties of the granules are more important for the quality of the tablets than the settings of the tabletting machine. The center point was also found to be close to an optimal tablet performance. To confirm the robustness of the tabletting domain four experiments were run, including two noise variables (humidity and temperature) set at the extremes. The resulting PLS model showed very good predictability for most of the factors.

The most critical issue to organ transplantation is the identification of new sources of organs. The present manuscript illustrates the state-of-the-art regenerative medicine (RM) investigations aiming to manufacturing abdominal organs for transplant purposes.This manuscript focuses on research in the bioengineering and regeneration of kidneys, insulin-producing cells, livers and small bowel. The main technology currently under development exploits the seeding of cells on supporting scaffolding material. Despite favorable preliminary results obtained with relatively simple, hollow organs, when more complex organs are considered, the scenario changes dramatically. Investigations are still in early stages, and clinical translation is not yet foreseeable based on current knowledge and information. Obstacles are numerous but we believe the critical factor hampering success is lack of in-depth understanding of the extracellular matrix (ECM) and cell-ECM interactions, as well as the mechanisms with which organs develop in utero.The success of RM to generate transplantable abdominal organs relies heavily on progress in (stem) cell therapies, developmental and ECM biology, and in the thorough understanding of the intricate relationship and interplay between cells and the ECM. This will require enormous investments in financial and medical resources, which ideally should be embarked upon by governments, the private sector and academia.

We investigated the biomechanical changes that occur in the lower limb following total knee arthroplasty (TKA). Lower limb joint kinematics and kinetics were evaluated in 32 patients before and 12 months following TKA and 28 age-matched controls. Analysis of variance with Bonferroni-adjusted post-hoc tests showed no significant changes in knee joint kinematics and kinetics following TKA despite significant improvements in pain and function. Significant increases in peak ankle plantarflexion and dorsiflexion moments and ankle power generation were observed which may be a compensatory response to impaired knee function to allow sufficient power generation for propulsion. Differences in knee gait parameters may arise as a result of the presence of osteoarthritis and mechanical changes associated with TKA as well as retention of the pre-surgery gait pattern.

Background Knee malalignment and variations in foot posture and function affect the forces transmitted through the knee joint and are associated with knee pain and medial tibiofemoral cartilage damage [1]. However, it is unclear whether altered foot posture and function are a compensatory mechanism to accommodate knee malalignment. Therefore, this study investigated changes in foot posture and function after realignment of the knee following total knee replacement (TKR) in people with medial compartment knee OA.

Background Individuals with knee osteoarthritis (OA) have flatter/more pronated feet than those without OA, but it is unclear whether altered foot posture and function are a cause or consequence of knee OA. The purpose of this study was to examine whether changes in foot posture and function occur after realignment of the knee following total knee replacement (TKR). Materials and methods Nineteen patients with predominantly medial compartment knee OA were tested prior to and 12 months after TKR. The Foot Posture Index (FPI) and Arch Index (AI) were measured as well as motion of the tibia, rearfoot and forefoot using a 3D motion analysis system incorporating a multisegment foot model. Results There were no significant changes in FPI or AI following TKR, however gait analysis revealed significant increases in tibial external rotation (− 18.7 ± 7.0° vs − 22.5 ± 8.7°, p = 0.002), tibial transverse plane range of motion (− 9.1 ± 4.6° vs − 11.4 ± 6.1°, p = 0.0028) and rearfoot range of motion in the frontal plane (8.6 ± 2.6° vs 10.4 ± 2.7°, p = 0.002), and a decrease in rearfoot transverse plane range of motion (8.7 ± 5.3° vs 5.9 ± 4.1°, p = 0.038) following the procedure. Conclusions TKR produces no change in static foot posture, but results in significant changes in rearfoot kinematics during gait. These findings suggest that rearfoot motion compensates for changes in the alignment of the knee, highlighting the ability of the foot to accommodate for proximal skeletal malalignment.

Objective Patients with knee osteoarthritis (OA) are characterized by increased muscle inflammation and altered gait. We investigated the association between proinflammatory mediators in the vastus lateralis and physical function and gait in patients with knee OA. Methods Nineteen patients with knee OA underwent gait analysis, assessment of self-reported pain and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), and a muscle biopsy that was taken during their knee replacement surgery. Muscle was analyzed for cellular protein inflammatory mediators, interleukin-6, monocyte chemotactic protein 1 (MCP-1), p65 NF-κB, signal transducer and activator of transcription 3 (STAT-3), and JNK-1. Sagittal plane knee function, including early stance knee range of motion (ROM) and knee sagittal plane impulse, was measured using a motion analysis system. Pearson's correlation was used to assess relationships between selected variables. Results Significant positive correlations were found between MCP-1 and self-perceived stiffness, physical function, and the total WOMAC score (P < 0.05). MCP-1 was also negatively correlated with early stance knee ROM (r = −0.52, P = 0.023). Reduced velocity was associated with elevated levels of p65 NF-κB and STAT-3 (P < 0.05). Knee sagittal plane impulse was negatively correlated with JNK-1 (P = 0.02), indicating reduction in knee impulse with an increased level of JNK-1. Conclusion Increased levels of several proinflammatory mediators were correlated with altered knee function during walking as well as greater physical disability and slower gait velocity. Identification of the cellular and molecular mechanisms associated with muscle inflammation is important to better understand the underlying mechanism responsible for altered gait and function in patients with knee OA.

Increased inflammation and pain are inseparable parts of knee osteoarthritis (OA) that may lead to disuse of the affected limb. The aim of this study was to examine the effects of knee OA on inflammation- and atrophy-related genes and proteins in the vastus lateralis muscle of patients with knee OA. Methods Nineteen patients with knee OA and 14 asymptomatic control subjects matched for age and body mass index underwent strength measurements and a muscle biopsy. Muscle was analyzed for the total cellular protein of inflammatory kinases (p65 NF-κB, JNK1/2, STAT-3, and suppressor of cytokine signaling 3 [SOCS-3]) and inflammatory intracellular molecules (interleukin-6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1], tumor necrosis factor [TNF], IL-1β, and atrogin-1). Results Knee OA resulted in greater levels of IL-6 protein (34%; P = 0.002). The levels of inflammatory kinases, including STAT-3 (187%; P = 0.002), p65 NF-κB (156%; P = 0.002), and JNK1 (179%; P = 0.027), were also elevated. Furthermore, elevated expression of gene transcripts encoding MCP-1 (28%; P = 0.023), TNF (85%; P < 0.001), and SOCS-3 (38%; P = 0.055) was observed in patients with knee OA compared with control subjects. Patients with knee OA had reduced muscle strength compared with control subjects (mean ± SEM 84.7 ± 8.7 versus 143.1 ± 20.8 Nm; P = 0.005). Negative correlations were observed between muscle strength and MCP-1 protein abundance (r = −0.37 [P = 0.042]) and the gene expression of TNF and atrogin-1 messenger RNA (r = −0.46 [P = 0.012] and r = −0.36 [P = 0.040], respectively). Conclusion Gene expression and the protein abundance of numerous muscle markers of inflammation and atrophy were elevated in patients with knee OA, and the increase in muscle inflammation was associated with a reduction in muscle strength. Given the role inflammation markers may play in muscle strength and atrophy, further studies are needed to investigate the effect of exercise intervention on skeletal muscle inflammation.

Knee pain and disability can persist following knee replacement surgery which may place patients at increased risk of falls. This study investigated the falls risk and the occurrence of falls of people with knee osteoarthritis (OA) before and at 12 months following knee replacement surgery. Thirty-five patients with knee OA were tested prior to undergoing knee replacement surgery and at 12 months following surgery using the short form Physiological Profile Assessment, which incorporates tests of vision, lower limb proprioception, knee extension strength, reaction time and postural sway. Physical activity, number of falls, fear of falling, pain, disability and health-related quality of life were also assessed. No significant differences were found between the number of falls pre- and post-surgery (n.s.), with 48.5 and 40% reporting at least one fall in the 12 months before and following the surgery, respectively. Improvements in knee strength, reaction time and fear of falling were evident following surgery, with no improvement in lower limb proprioception. Self-reported pain, function and stiffness were significantly improved, but health-related quality of life deteriorated following the surgery. The number of falls experienced following knee replacement surgery remained relatively high, which may be attributed to the persistence of impaired lower limb proprioception. Although knee replacement surgery improves function and alleviates pain, people who undergo this procedure may need to engage in rehabilitation following the surgery to reduce the risk of falling. Therapeutic study investigating the result of treatment on patient outcomes, Level IV.

Background Neuroimaging studies in late life depression have reported decreased structural integrity of white matter tracts in the prefrontal cortex. Functional studies have identified changes in functional connectivity among several key areas involved in mood regulation. Few studies have combined structural and functional imaging. In this study we sought to examine the relationship between the uncinate fasciculus, a key fronto-temporal tract and resting state functional connectivity between the ventral prefrontal cortex ((PFC) and limbic and striatal areas. Methods The sample consisted of 24 older patients remitted from unipolar major depression. Each participant had a magnetic resonance imaging brain scan using standardized protocols to obtain both diffusion tensor imaging and resting state functional connectivity data. Our statistical approach compared structural integrity of the uncinate fasciculus and functional connectivity data. Results We found positive correlations between left uncinate fasciculus (UF) fractional anisotropy (FA) and resting state functional connectivity (rsFC) between the left ventrolateral PFC and left amygdala and between the left ventrolateral PFC and the left hippocampus. In addition, we found a significant negative correlation between left ventromedial PFC-caudate rsFC and left UF FA. The right UF FA did not correlate with any of the seed region based connectivity. Conclusions These results support the notion that resting state functional connectivity reflects structural integrity, since the ventral PFC is structurally connected to temporal regions by the UF. Future studies should include larger samples of patients and healthy comparison subjects in which both resting state and task-based functional connectivity are examined.

Single layer honeycomb strip chambers have been constructed for the tracking calorimeter TRACAL. This detector is a component of the RD5 experimental test setup at CERN, where aspects of muon detection in LHC conditions are studied. The construction of the chambers is described and the excellent spatial resolution obtained from strip signals (σ

In 1989 the Tel Aviv University Department of Nursing introduced a non-thesis option for the master's degree. This decision was reached in order to enable students who so wished to undertake a major practice project instead of a research study, and to promote involvement in health policy development. Projects focused on health policy issues in administration, education or clinical practice. Students participated in a weekly seminar and conducted field work under the guidance of an expert practitioner/tutor. Evaluation of the project revealed greater awareness of policy issues, high satisfaction by students, faculty and tutors, increase of student admissions by 50%, and enhanced partnership between the university and nursing service/education in the community.

We investigated the feasibility of breast conserving treatment (BCT) in patients with large (T2, T3) breast cancers, by combining preoperative radiotherapy and tissue replacement after wide excision by a myosubcutaneous flap transposition. The treatment consisted of 50 Gy whole breast irradiation followed by a 15-25 Gy iridium implant to the primary tumour with 2 cm margins. Four weeks after completion of the radiotherapy, wide excision of the original tumour area with a 1 cm margin and an axillary dissection was performed. In the same session the breast was reconstructed with an ipsilateral latissimus dorsi transposition flap. The treatment results in the first 6 patients are encouraging with respect to treatment toxicity and cosmetic outcome. The clinical tumour response after radiotherapy was difficult to evaluate. However, microscopic evaluation showed residual tumour in all specimens with (focal) involvement of the surgical margins in two. With a minimum follow-up of over 2.5 years no tumour recurrences in the breast have occurred.