Low-elevation conifers in California's Sierra Nevada are out of equilibrium with climate.

Since the 1930s, California's Sierra Nevada has warmed by an average of 1.2 ∘ C. Warming directly primes forests for easier wildfire ignition, but the change in climate also affects vegetation species composition. Different types of vegetation support unique fire regimes with distinct probabilities of catastrophic wildfire, and anticipating vegetation transitions is an important but undervalued component of long-term wildfire management and adaptation. Vegetation transitions are more likely where the climate has become unsuitable but the species composition remains static. This vegetation climate mismatch (VCM) can result in vegetation conversions, particularly after a disturbance like wildfire. Here we produce estimates of VCM within conifer-dominated forests in the Sierra Nevada. Observations from the 1930s Wieslander Survey provide a foundation for characterizing the historical relationship between Sierra Nevada vegetation and climate before the onset of recent, rapid climate change. Based on comparing the historical climatic niche to the modern distribution of conifers and climate, ∼19.5% of modern Sierra Nevada coniferous forests are experiencing VCM, 95% of which is below an elevation of 2356 m. We found that these VCM estimates carry empirical consequences: likelihood of type-conversion increased by 9.2% for every 10% decrease in habitat suitability. Maps of Sierra Nevada VCM can help guide long-term land management decisions by distinguishing areas likely to transition from those expected to remain stable in the near future. This can help direct limited resources to their most effective uses-whether it be protecting land or managing vegetation transitions-in the effort to maintain biodiversity, ecosystem services, and public health in the Sierra Nevada.

Forest fires and climate-induced tree range shifts in the western US.

Due to climate change, plant populations experience environmental conditions to which they are not adapted. Our understanding of the next century's vegetation geography depends on the distance, direction, and rate at which plant distributions shift in response to a changing climate. In this study we test the sensitivity of tree range shifts (measured as the difference between seedling and mature tree ranges in climate space) to wildfire occurrence, using 74,069 Forest Inventory Analysis plots across nine states in the western United States. Wildfire significantly increased the seedling-only range displacement for 2 of the 8 tree species in which seedling-only plots were displaced from tree-plus-seedling plots in the same direction with and without recent fire. The direction of climatic displacement was consistent with that expected for warmer and drier conditions. The greater seedling-only range displacement observed across burned plots suggests that fire can accelerate climate-related range shifts and that fire and fire management will play a role in the rate of vegetation redistribution in response to climate change.

Muscle activation and heart rate responses to a side-step interval exercise.

BACKGROUND: The side-step test is commonly used to assess agility. Side-step interval exercise may also be a potential way to improve cardiorespiratory and muscular fitness. However, the acute heart rate and muscle activation response to this type of exercise is not well established. In addition, different tempos can influence these responses. The purpose of this study was to determine the acute heart rate and muscle activation responses of a side-step interval exercise to different exercise tempos. METHODS: Ten participants completed a V˙O2 max test and performed a side-step interval exercise for 4 × 1 min intervals separated by 1-min rest intervals at a slow (84 bpm) and fast (112 bpm) tempo. Muscle activation of the vastus lateralis and vastus medialis and heart rate were measured during exercise. RESULTS: During the slow tempo, vastus lateralis muscle activation varied from 45% to 48% of maximum muscle activation (EMGmax ) while vastus medialis muscle activation varied from 51% to 54% EMGmax . During the fast tempo, vastus lateralis muscle activation varied from 53% to 65% EMGmax while vastus medialis muscle activation varied from 64% to 76% EMGmax . Heart rates varied from 80-84% HRmax from set 1 to set 4 for the fast tempo and varied from 67% to 72% HRmax from set 1 to set 4 for the slow speeds. CONCLUSION: Exercise intensity of a side-step interval exercise reached adequate levels to suggest that it may be possible to use this type of exercise to improve cardiorespiratory and muscular fitness.

Clinicopathologic features of lingual canine T-zone lymphoma.

Canine T-zone lymphoma (TZL) is a subtype of T-cell lymphoma characterized by unique histologic pattern and cytomorphology, immunophenotypic loss of CD45 expression, and an indolent clinical behaviour. Dogs with TZL typically present with 1 or more enlarged lymph nodes and/or lymphocytosis. We describe a novel extranodal presentation of TZL involving the tongue. Twelve dogs with tongue masses were diagnosed with lingual TZL based on a variable combination of immunophenotyping via flow cytometry, cytology, histopathology, immunohistochemistry and/or PCR for antigen receptor rearrangement (PARR) assay. Eleven dogs exhibited concurrent lymphocytosis and/or lymph node enlargement. Three cases were initially diagnosed as plasma cell tumours based on histology alone, thereby revealing a potential diagnostic challenge. Seven dogs achieved clinical remission and 4 achieved stable disease following variable treatment, consistent with the indolent nature of typical TZL involving the lymph nodes and peripheral blood. In 1 case the TZL resulted in progressive disease and failure to respond to treatment. In this case, the TZL exhibited histologic features of a higher grade neoplasm. This case series highlights a unique presentation of TZL and identifies a new differential diagnosis for lingual neoplasia. In this study, we characterize the clinical presentation, diagnostic features and patient outcomes of 12 dogs with lingual TZL.

Evaluation of the age-dependent dosing recommendations for the administration of daily tinzaparin in children with thrombosis.

Essentials The once-daily dosing of tinzaparin provides an advantage over other low molecular weight heparins. The recommended age-dependent doses of tinzaparin in children have not previously been validated. Once-daily administration of tinzaparin is a safe and effective treatment of childhood thrombosis. Recommended doses are appropriate but monitoring may be required due to inter-individual variation. SUMMARY: Background The recommended starting doses of tinzaparin for the treatment of thrombosis in children have not previously been validated. There are few data to support the efficacy and safety of once-daily tinzaparin dosing in children with thrombosis. Objectives To investigate the use of tinzaparin for the treatment of childhood thrombosis, and to evaluate the age-dependent dosing recommendations and define outcomes in terms of efficacy and safety. Methods This was a retrospective cohort study of children aged 0 to < 16 years treated for thrombosis at a large teaching hospital in the UK between 2008 and 2015. Medical records were reviewed to evaluate tinzaparin dosing, anti-activated factor X (FXa) levels, and patient outcomes. Results Seventy-nine children were identified as having received tinzaparin. Dosing information was available for 57. Younger children required higher doses to reach a therapeutic level. The therapeutic dose requirement varied within age groups, supporting the use of anti-FXa monitoring. Over a median follow-up of 35 months, there were 13 (16%) bleeding episodes (two major; seven clinically relevant but non-major; and four minor). There were two (3%) recurrent episodes of thrombosis. Children were treated for a median duration of 3 months, and the majority (86%) remained on tinzaparin for the duration of their anticoagulant therapy. Conclusion Once-daily tinzaparin is a safe and effective treatment for childhood thrombosis, with rates of recurrence and bleeding similar to those for other anticoagulants used in children. The recommended starting doses are appropriate, but anti-FXa monitoring may be required, owing to interindividual variability in the therapeutic dose requirement.

Does bariatric surgery prevent progression of diabetic retinopathy?

PurposeTo assess the changes in diabetic retinopathy (DR) in type 2 diabetes (T2DM) patients post bariatric surgery and report on the risk factors that may be associated with it.Patients and methodsRetrospective observational study of T2DM patients who underwent bariatric surgery in a UK specialist bariatric unit between 2009 and 2015. Preoperative and postoperative weight, HbA1c, and annual DR screening results were collected from medical records. Patients with preoperative retinal screening and at least one postoperative retinal screening were eligible for analysis. Multivariate analysis was used to explore significant clinical predictors on postoperative worsening in DR.ResultsA total of 102 patients were eligible for analysis and were followed up for 4 years. Preoperatively, 68% of patients had no DR compared to 30% with background retinopathy, 1% pre-proliferative retinopathy, and 1% proliferative retinopathy. In the first postoperative visit, 19% of patients developed new DR compared to 70% stable and 11% improved. These proportions remained similar for each postoperative visit over time. Young age, male gender, high preoperative HbA1c, and presence of preoperative retinopathy were the significant predictors of worsening postoperatively.ConclusionBariatric surgery does not prevent progression of DR. Young male patients with pre-existing DR and poor preoperative glycaemic control are most at risk of progression. All diabetic patients should attend regular DR screening post bariatric surgery to allow early detection of potentially sight-threatening changes, particularly among those with identifiable risk factors. Future prospective studies with prolonged follow-up are required to clarify the duration of risk.

BCL2 and MYC are expressed at high levels in canine diffuse large B-cell lymphoma but are not predictive for outcome in dogs treated with CHOP chemotherapy.

Diffuse large B-cell lymphoma (DLBCL) is the most common haematopoietic malignancy in dogs. Recently, MYC and BCL2 expression levels determined with immunohistochemistry (IHC) were found to be prognostic in people with DLBCL. We hypothesized that canine DLBCL can be similarly subdivided into prognostic subtypes based on expression of MYC and BCL2. Cases of canine DLBCL treated with CHOP chemotherapy were retrospectively collected and 43 dogs had available histologic tissue and complete clinical follow-up. Median values of percent immunoreactive versus immunonegative cells were used to determine positive or negative expression status. Completion of CHOP was significantly associated with a positive outcome. Compared with human patients, our canine DLBCL patients had high IHC expression of both MYC and BCL2, and relative expression levels of one or both markers were not associated with clinical outcome.

European canine lymphoma network consensus recommendations for reporting flow cytometry in canine hematopoietic neoplasms.

BACKGROUND: Flow cytometry (FC) is assuming increasing importance in diagnosis in veterinary oncology. The European Canine Lymphoma Network (ECLN) is an international cooperation of different institutions working on canine lymphoma diagnosis and therapy. The ECLN panel of experts on FC has defined the issue of reporting FC on canine lymphoma and leukemia as their first hot topic, since a standardized report that includes all the important information is still lacking in veterinary medicine. METHODS: The flow cytometry panel of the ECLN started a consensus initiative using the Delphi approach. Clinicians were considered the main target of FC reports. A panel of experts in FC was interrogated about the important information needed from a report. RESULTS: Using the feedback from clinicians and subsequent discussion, a list of information to be included in the report was made, with four different levels of recommendation. The final report should include both a quantitative part and a qualitative or descriptive part with interpretation of the salient results. Other items discussed included the necessity of reporting data regarding the quality of samples, use of absolute numbers of positive cells, cutoff values, the intensity of fluorescence, and possible aberrant patterns of antigen expression useful from a clinical point of view. CONCLUSION: The consensus initiative is a first step toward standardization of diagnostic approach to canine hematopoietic neoplasms among different institutions and countries. This harmonization will improve communication and patient care and also facilitate the multicenter studies necessary to further our knowledge of canine hematopoietic neoplasms. © 2016 International Clinical Cytometry Society.

The clinical implications of metal debris release from the taper junctions and bearing surfaces of metal-on-metal hip arthroplasty: joint fluid and blood metal ion concentrations.

AIMS: We wished to investigate the influence of metal debris exposure on the subsequent immune response and resulting soft-tissue injury following metal-on-metal (MoM) hip arthroplasty. Some reports have suggested that debris generated from the head-neck taper junction is more destructive than equivalent doses from metal bearing surfaces. PATIENTS AND METHODS: We investigated the influence of the source and volume of metal debris on chromium (Cr) and cobalt (Co) concentrations in corresponding blood and hip synovial fluid samples and the observed agglomerated particle sizes in excised tissues using multiple regression analysis of prospectively collected data. A total of 199 explanted MoM hips (177 patients; 132 hips female) were analysed to determine rates of volumetric wear at the bearing surfaces and taper junctions. RESULTS: The statistical modelling suggested that a greater source contribution of metal debris from the taper junction was associated with smaller aggregated particle sizes in the local tissues and a relative reduction of Cr ion concentrations in the corresponding synovial fluid and blood samples. Metal debris generated from taper junctions appears to be of a different morphology, composition and therefore, potentially, immunogenicity to that generated from bearing surfaces. CONCLUSION: The differences in debris arising from the taper and the articulating surfaces may provide some understanding of the increased incidence of soft-tissue reactions reported in patients implanted with MoM total hip arthroplasties compared with patients with hip resurfacings. Cite this article: Bone Joint J 2016;98-B:925-33.

Predicting macular hole closure with ocriplasmin based on spectral domain optical coherence tomography.

PurposeTo assess the preoperative features of patients with idiopathic macular hole (IMH) and vitreomacular adhesion (VMA) treated with ocriplasmin (OCP) that can predict successful closure.MethodData were prospectively collected on all patients with IMH treated with OCP in three British ophthalmic centres. Several preoperative variables were recorded including the IMH base diameter (BD), minimum linear diameter (MLD), and VMA width measured on spectral domain optical coherence tomography. Several other IMH indices were derived including a 'width factor', defined as the BD minus the MLD in µm. The occurrence of VMA release and hole closure were used as the main outcome measures.ResultsThirty-three patients in total with IMH were treated with OCP. Two patients developed rhegmatogenous retinal detachment and were excluded. The mean age of the remaining 31 patients was 71 years, and 71% were female. VMA release occurred in 19 of the 31 (61%) patients and macular hole closure in 11 (35%). Width factor was the most predictive feature for closure on multivariate analysis. The deviance R(2) was 67% (P<0.001). An IMH with a width factor of <60 µm had a 95% certainty of closure, whereas if >290 µm then there was less than a 5% chance of closure. Neither VMA width nor MLD alone was associated with VMA release or closure.ConclusionsPatients with macular holes where the BD was close in size to the MLD had an improved probability of closure than holes with wider base configurations.

Influence of CYP2C9 polymorphism on the fall in International Normalized Ratio in patients interrupting warfarin therapy before elective surgery.

BACKGROUND: Patients on warfarin are normally required to stop treatment for a fixed number of days prior to an invasive procedure. However, the anticoagulant activity of warfarin subsides at different rates among different patients. OBJECTIVES: The aim of this study was to investigate the potential influence of CYP2C9 polymorphism on the variable rate of fall in the International Normalized Ratio (INR) in patients withdrawing from warfarin treatment prior to elective surgery. PATIENTS/METHODS: One hundred and fifty-two patients aged 43-93 years were recruited. Demographic data on age, height, weight, gender, daily warfarin dose, indication for anticoagulation therapy, medical diagnosis, surgical operation planned and concomitant medication were recorded. A blood sample was taken for later CYP2C9 genotyping. RESULTS: For patients with two CYP2C9 variant alleles (CYP2C9*2*2 or CYP2C9*2*3), the odds of having an INR of ≥ 1.5 before the planned day of surgery were 8.64 times greater (95% confidence interval [CI] 2.25-33.25) than for other patients. Multiple regression analysis revealed that the rate of fall in the INR was reduced in the presence of two CYP2C9 variant alleles, as well as increasing patient age, weight and number of comorbidities, and increased with increasing initial INR (F5,132  = 242.9, P < 0.0001), all of which accounted for ~ 90% of the interindividual variability in the fall in INR. CONCLUSION: A genotype-guided protocol to tailor warfarin withdrawal according to an individual patient's CYP2C9 genotype could reduce cancellation or delays of planned procedures, and could also be beneficial when transitioning patients from warfarin to one of the new oral anticoagulants.

Canine T-zone lymphoma: unique immunophenotypic features, outcome, and population characteristics.

BACKGROUND: Canine T-cell lymphoma (TCL) is clinically and histologically heterogeneous with some forms, such as T-zone lymphoma (TZL), having an indolent course. Immunophenotyping is an important tool in the classification of TCL in people, and can be equally useful in dogs. HYPOTHESIS/OBJECTIVES: We hypothesized that loss of expression of the CD45 antigen is a specific diagnostic feature of TZL. ANIMALS: Twenty dogs with concurrent histology and immunophenotyping by flow cytometry were studied in depth. An additional 494 dogs diagnosed by immunophenotyping were used to characterize the population of dogs with this disease. METHODS: Lymph node biopsies from 35 dogs with TCL were classified by 2 pathologists using WHO criteria. Twenty lymph nodes were from dogs with CD45- TCL and 15 were from CD45+ TCL. The pathologists were blinded to the flow cytometry findings. Outcome information was sought for the 20 dogs with CD45- lymphoma, and population characteristics of the additional 494 dogs were described. RESULTS: All 20 CD45- cases were classified as TZL. The 15 CD45+ cases were classified as aggressive TCL and are described in an accompanying paper. TZL cases had a median survival of 637 days. Examination of 494 additional dogs diagnosed with TZL by immunophenotyping demonstrated that 40% of cases are in Golden Retrievers, are diagnosed at a median age of 10 years, and the majority have lymphadenopathy and lymphocytosis. CONCLUSIONS: TZL has unique immunophenotypic features that can be used for diagnosis.

Flow cytometric characterization and clinical outcome of CD4+ T-cell lymphoma in dogs: 67 cases.

BACKGROUND: Canine T-cell lymphoma (TCL) is conventionally considered an aggressive disease, but some forms are histologically and clinically indolent. CD4 TCL is reported to be the most common subtype of TCL. We assessed flow cytometric characteristics, histologic features when available, and clinical outcomes of CD4+ TCL to determine if flow cytometry can be used to subclassify this group of lymphomas. OBJECTIVE: To test the hypothesis that canine CD4+ T-cell lymphoma (TCL) is a homogeneous group of lymphomas with an aggressive clinical course. ANIMALS: Sixty-seven dogs diagnosed with CD4+ TCL by flow cytometry and treated at 1 of 3 oncology referral clinics. METHODS: Retrospective multivariable analysis of outcome in canine CD4+ TCL including patient characteristics, treatment, and flow cytometric features. RESULTS: The majority of CD4+ TCL were CD45+, expressed low class II MHC, and exhibited an aggressive clinical course independent of treatment regimen (median survival, 159 days). Histologically, CD4+ TCL were classified as lymphoblastic or peripheral T cell. Size of the neoplastic lymphocytes had a modest effect on both PFI and survival in this group. A small number of CD4+ TCL were CD45- and class II MHC high, and exhibited an apparently more indolent clinical course (median survival not yet reached). CONCLUSIONS AND CLINICAL IMPORTANCE: Although the majority of CD4+ TCL in dogs had uniform clinical and flow cytometric features and an aggressive clinical course, a subset had a unique immunophenotype that predicts significantly longer survival. This finding strengthens the utility of flow cytometry to aid in the stratification of canine lymphoma.

The effect of surgical factors on early patient-reported outcome measures (PROMS) following total knee replacement.

Patient-reported outcome measures (PROMs) are increasingly being used to assess functional outcome and patient satisfaction. They provide a framework for comparisons between surgical units, and individual surgeons for benchmarking and financial remuneration. Better performance may bring the reward of more customers as patients and commissioners seek out high performers for their elective procedures. Using National Joint Registry (NJR) data linked to PROMs we identified 22,691 primary total knee replacements (TKRs) undertaken for osteoarthritis in England and Wales between August 2008 and February 2011, and identified the surgical factors that influenced the improvements in the Oxford knee score (OKS) and EuroQol-5D (EQ-5D) assessment using multiple regression analysis. After correction for patient factors the only surgical factors that influenced PROMs were implant brand and hospital type (both p < 0.001). However, the effects of surgical factors upon the PROMs were modest compared with patient factors. For both the OKS and the EQ-5D the most important factors influencing the improvement in PROMs were the corresponding pre-operative score and the patient's general health status. Despite having only a small effect on PROMs, this study has shown that both implant brand and hospital type do influence reported subjective functional scores following TKR. In the current climate of financial austerity, proposed performance-based remuneration and wider patient choice, it would seem unwise to ignore these effects and the influence of a range of additional patient factors.

Comparison of patient-reported outcome measures following total and unicondylar knee replacement.

Following arthroplasty of the knee, the patient's perception of improvement in symptoms is fundamental to the assessment of outcome. Better clinical outcome may offset the inferior survival observed for some types of implant. By examining linked National Joint Registry (NJR) and patient-reported outcome measures (PROMs) data, we aimed to compare PROMs collected at a minimum of six months post-operatively for total (TKR: n = 23,393) and unicondylar knee replacements (UKR: n = 505). Improvements in knee-specific (Oxford knee score, OKS) and generic (EuroQol, EQ-5D) scores were compared and adjusted for case-mix differences using multiple regression. Whereas the improvements in the OKS and EQ-5D were significantly greater for TKR than for UKR, once adjustments were made for case-mix differences and pre-operative score, the improvements in the two scores were not significantly different. The adjusted mean differences in the improvement of OKS and EQ-5D were 0.0 (95% confidence interval (CI) -0.9 to 0.9; p = 0.96) and 0.009 (95% CI -0.034 to 0.015; p = 0.37), respectively. We found no difference in the improvement of either knee-specific or general health outcomes between TKR and UKR in a large cohort of registry patients. With concerns about significantly higher revision rates for UKR observed in worldwide registries, we question the widespread use of an arthroplasty that does not confer a significant benefit in clinical outcome.

A proposal for an individualized pharmacogenetics-based warfarin initiation dose regimen for patients commencing anticoagulation therapy.

A significant proportion of the interindividual variability in warfarin dose requirements can be explained on the basis of CYP2C9 and VKORC1 genotypes. We report the development of a novel pharmacogenetics-based 3-day warfarin initiation dose (ID) algorithm based on the International Warfarin Pharmacogenetics Consortium (IWPC) maintenance dose algorithm and the CYP2C9 genotype-based variance in warfarin half-life. The predictive value of the pharmacogenetics-based ID was assessed in a large cohort of 671 newly diagnosed patients with thromboembolic disorders who were about to commence anticoagulation therapy in accordance with standard induction regimens. In patients with mean international normalized ratio (INR)days 4-7>4.0 (n=63) after warfarin initiation, the pharmacogenetics-based ID algorithm predicted a markedly lower dose requirement (median reduction=4.2 mg), whereas in those with mean INRdays 4-7<2.0 (n=145), the predicted dose requirement was very similar to that in the standard regimen. The use of a pharmacogenetics-based ID may avoid overshooting of INR in warfarin-sensitive patients without unduly affecting the time taken to reach target range in the majority of patients.

Class II major histocompatibility complex expression and cell size independently predict survival in canine B-cell lymphoma.

BACKGROUND: Class II major histocompatibility complex (MHC) is an independent predictor of outcome in human B-cell lymphoma. We assessed class II expression together with other markers for their impact on prognosis in canine B-cell lymphoma. HYPOTHESIS: Low class II MHC expression, large cell size, and expression of CD34 will predict a poorer outcome in canine B-cell lymphoma. Expression of CD5 and CD21 on tumor cells also may be associated with outcome. ANIMALS: One hundred and sixty dogs with cytologically confirmed lymphoma. METHODS: Patient signalment, treatment type, and flow cytometry characteristics were analyzed for their influence on outcome. A multivariable predictive model of survival was generated using 2/3 of the patients and validated on the remaining 1/3 of the dataset. RESULTS: Class II MHC expression had a negative association with mortality and relapse. Treatment type also influenced relapse and mortality, whereas cell size and patient age was only associated with mortality. CD34, CD21, and CD5 expression was not associated with disease outcome. The constructed model performed variably in predicting the validation group's outcome at the 6-month time point. CONCLUSIONS AND CLINICAL IMPORTANCE: Low levels of class II MHC expression on B-cell lymphoma predict a poor outcome, as in human B-cell lymphoma. This finding has implications for the use of dogs to model human lymphomas. Class II expression, cell size, treatment, and age can be combined to predict mortality with a high level of specificity.