Comparison of contrast-enhanced videofluoroscopy to unenhanced dynamic MRI in minor patients following surgical correction of velopharyngeal dysfunction.

OBJECTIVES: To compare dynamic magnetic resonance imaging (MRI) with videofluoroscopy (VFS) regarding image quality and assessment of gap size between soft palate (SP) and posterior pharyngeal wall (PPW) in children and adolescents following surgical correction of velopharyngeal dysfunction (VPD). METHODS: Twenty-one patients undergoing unenhanced 3-T MRI and contrast-enhanced VFS were included in this IRB-approved prospective study. The MRI scan protocol comprised refocused gradient-echo sequences in transverse and sagittal planes during speech, with TE 1.97 ms, TR 3.95 ms, flip angle 8°, matrix size 128 × 128, and 5-mm slice thickness. Radial k-space sampling and sliding window reconstruction were used to achieve an image acquisition rate of 28 frames per second (fps). VFS with 30 fps was similarly performed in both planes. Closure of the velopharyngeal port during phonation was evaluated by two experienced radiologists. RESULTS: Eleven (52.4%) patients displayed a complete closure, whereas ten (47.6%) patients showed a post-operative gap during speech. VFS and MRI equally identified the cases with persistent or recurrent VPD. Differences in SP-PPW distance between VFS (3.9 ± 1.6 mm) and MRI (4.1 ± 1.5 mm) were not statistically significant (p = 0.5). The subjective overall image quality of MRI was rated inferior (p < 0.001) compared with VFS, with almost perfect inter-rater agreement (κ = 0.90). The presence of susceptibility artifacts did not limit anatomical measurements. CONCLUSION: Dynamic MRI is equally reliable as VFS to assess persistent or recurrent inadequate velum closure in patients following surgical treatment of VPD. KEY POINTS: • Unenhanced 3-T dynamic MRI and contrast-enhanced videofluoroscopy are equally useful for the identification of patients with incomplete velopharyngeal closure during speech. • MRI using refocused gradient-echo acquisition with radial k-space sampling and sliding window reconstruction generates diagnostic images with 28 frames per second. • MRI can offer a radiation-free alternative to currently established videofluoroscopy for young patients.

Are cost advantages from a modern Indian hospital transferable to the United States?

BACKGROUND: Multiple modern Indian hospitals operate at very low cost while meeting US-equivalent quality accreditation standards. Though US hospitals face intensifying pressure to lower their cost, including proposals to extend Medicare payment rates to all admissions, the transferability of Indian hospitals' cost advantages to US peers remains unclear. METHODS: Using time-driven activity-based costing methods, we estimate the average cost of personnel and space for an elective coronary artery bypass graft (CABG) surgery at two American hospitals and one Indian hospital (NH). All three hospitals are Joint Commission accredited and have reputations for use of modern performance management methods. Our case study applies several analytic steps to distinguish transferable from non-transferable sources of NH's cost savings. RESULTS: After removing non-transferable sources of efficiency, NH's residual cost advantage primarily rests on shifting tasks to less-credentialed and/or less-experienced personnel who are supervised by highly-skilled personnel when perceived risk of complications is low. NH's high annual CABG volume facilitates such supervised work "downshifting." The study is subject to limitations inherent in case studies, does not account for the younger age of NH's patients, or capture savings attributable to NH's negligible frequency of re-admission or post-acute care facility placement. CONCLUSIONS: Most transferable bases for a modern Indian hospital's cost advantage would require more flexible American states' hospital and health professional licensing regulations, greater family participation in inpatient care, and stronger support by hospital executives and clinicians for substantially lowering the cost of care via regionalization of complex surgeries and weekend use of costly operating rooms.

A shift of thermokarst lakes from carbon sources to sinks during the Holocene epoch.

Thermokarst lakes formed across vast regions of Siberia and Alaska during the last deglaciation and are thought to be a net source of atmospheric methane and carbon dioxide during the Holocene epoch. However, the same thermokarst lakes can also sequester carbon, and it remains uncertain whether carbon uptake by thermokarst lakes can offset their greenhouse gas emissions. Here we use field observations of Siberian permafrost exposures, radiocarbon dating and spatial analyses to quantify Holocene carbon stocks and fluxes in lake sediments overlying thawed Pleistocene-aged permafrost. We find that carbon accumulation in deep thermokarst-lake sediments since the last deglaciation is about 1.6 times larger than the mass of Pleistocene-aged permafrost carbon released as greenhouse gases when the lakes first formed. Although methane and carbon dioxide emissions following thaw lead to immediate radiative warming, carbon uptake in peat-rich sediments occurs over millennial timescales. We assess thermokarst-lake carbon feedbacks to climate with an atmospheric perturbation model and find that thermokarst basins switched from a net radiative warming to a net cooling climate effect about 5,000 years ago. High rates of Holocene carbon accumulation in 20 lake sediments (47 ± 10 grams of carbon per square metre per year; mean ± standard error) were driven by thermokarst erosion and deposition of terrestrial organic matter, by nutrient release from thawing permafrost that stimulated lake productivity and by slow decomposition in cold, anoxic lake bottoms. When lakes eventually drained, permafrost formation rapidly sequestered sediment carbon. Our estimate of about 160 petagrams of Holocene organic carbon in deep lake basins of Siberia and Alaska increases the circumpolar peat carbon pool estimate for permafrost regions by over 50 per cent (ref. 6). The carbon in perennially frozen drained lake sediments may become vulnerable to mineralization as permafrost disappears, potentially negating the climate stabilization provided by thermokarst lakes during the late Holocene.

Genetic investigation of equine recurrent uveitis in Appaloosa horses.

Equine recurrent uveitis (ERU) is characterized by intraocular inflammation that often leads to blindness in horses. Appaloosas are more likely than any other breed to develop insidious ERU, distinguished by low-grade chronic intraocular inflammation, suggesting a genetic predisposition. Appaloosas are known for their white coat spotting patterns caused by the leopard complex spotting allele (LP) and the modifier PATN1. A marker linked to LP on ECA1 and markers near MHC on ECA20 were previously associated with increased ERU risk. This study aims to further investigate these loci and identify additional genetic risk factors. A GWAS was performed using the Illumina Equine SNP70 BeadChip in 91 horses. Additive mixed model approaches were used to correct for relatedness. Although they do not reach a strict Bonferroni genome-wide significance threshold, two SNPs on ECA1 and one SNP each on ECA12 and ECA29 were among the highest ranking SNPs and thus warranted further analysis (P = 1.20 × 10-5 , P = 5.91 × 10-6 , P = 4.91 × 10-5 , P = 6.46 × 10-5 ). In a second cohort (n = 98), only an association with the LP allele on ECA1 was replicated (P = 5.33 × 10-5 ). Modeling disease risk with LP, age and additional depigmentation factors (PATN1 genotype and extent of roaning) supports an additive role for LP and suggests an additive role for PATN1. Genotyping for LP and PATN1 may help predict ERU risk (AUC = 0.83). The functional role of LP and PATN1 in ERU development requires further investigation. Testing samples across breeds with leopard complex spotting patterns and a denser set of markers is warranted to further refine the genetic components of ERU.

[Muscular injuries in the inguinal region including apophyseal injuries]. / Muskelverletzungen der Leistenregion einschließlich apophysärer Verletzungen.

BACKGROUND: Muscular and apophyseal injuries in the inguinal region are a common cause of groin pain in athletes. PURPOSE: Frequently occurring muscular and apophyseal injuries in the groin region are described. MATERIAL AND METHODS: Fundamental studies and expert recommendations are discussed. Examination protocols for routine clinical practice are presented. RESULTS: The exact diagnosis and classification of muscular or apophyseal injuries in the inguinal region are the basic prerequisites for the initiation of a targeted treatment and thus crucial for the return to sport time. These injuries are occurring with increasing frequency in both professional and recreational sports. CONCLUSION: In addition to the clinical examination and the history of the course of the injury, MRI plays an important role in the evaluation of muscular and apophyseal injuries in the inguinal region.

Generation of an equine biobank to be used for Functional Annotation of Animal Genomes project.

The Functional Annotation of Animal Genomes (FAANG) project aims to identify genomic regulatory elements in both sexes across multiple stages of development in domesticated animals. This study represents the first stage of the FAANG project for the horse, Equus caballus. A biobank of 80 tissue samples, two cell lines and six body fluids was created from two adult Thoroughbred mares. Ante-mortem assessments included full physical examinations, lameness, ophthalmologic and neurologic evaluations. Complete blood counts and serum biochemistries were also performed. At necropsy, in addition to tissue samples, aliquots of serum, ethylenediaminetetraacetic acid (EDTA) plasma, heparinized plasma, cerebrospinal fluid, synovial fluid, urine and microbiome samples from all regions of the gastrointestinal and urogenital tracts were collected. Epidermal keratinocytes and dermal fibroblasts were cultured from skin samples. All tissues were grossly and histologically evaluated by a board-certified veterinary pathologist. The results of the clinical and pathological evaluations identified subclinical eosinophilic and lymphocytic infiltration throughout the length of the gastrointestinal tract as well as a mild clinical lameness in both animals. Each sample was cryo-preserved in multiple ways, and nuclei were extracted from selected tissues. These samples represent the first published systemically healthy equine-specific biobank with extensive clinical phenotyping ante- and post-mortem. The tissues in the biobank are intended for community-wide use in the functional annotation of the equine genome. The use of the biobank will improve the quality of the reference annotation and allow all equine researchers to elucidate unknown genomic and epigenomic causes of disease.

Expression of cutaneous immunity markers during infant skin maturation.

BACKGROUND/OBJECTIVES: Infant skin undergoes a maturation process during the early years of life. Little is known about the skin's innate immunity. We investigated the dynamics of innate immunity markers collected from the surface of infant skin during the first 36 months of life. METHODS: A total of 117 healthy infants aged 3-36 months participated in the study. We extracted human beta defensin-1 and interleukin 1 alpha and its receptor antagonist using transdermal analysis patches from the skin surface of the posterior lower leg area. The extracts were analyzed using a spot enzyme-linked immunosorbent assay. RESULTS: Skin surface human beta defensin-1 levels were higher early in life and decreased with infant age. The ratio of interleukin 1 alpha receptor antagonist to interleukin 1 alpha did not change significantly with age but showed a distinct difference between sexes, with female infants having higher values than male infants. CONCLUSION: As is the case with skin structure and functional properties, cutaneous innate immunity also appears to undergo a maturation period during infancy, with innate immunity slowly declining as adaptive immunity takes over. Sex differences in immune markers may explain sex-dependent susceptibilities to infection.

[Insertional Achilles tendinopathy : Differentiated diagnostics and therapy]. / Ansatznahe Erkrankungen der Achillessehne : Differenzierte Diagnostik und Therapie.

Achilles tendinopathy at the calcaneal insertion is classified into insertional tendinopathy, retrocalcaneal and superficial bursitis. The aim of this study was to present the current evidence on conservative and surgical treatment of insertional tendinopathy of the Achilles tendon. Conservative first-line therapy includes reduction of activity levels, administration of non-steroidal anti-inflammatory drugs (NSAID), adaptation of footwear, heel wedges and orthoses or immobilization. In addition, further conservative therapy options are also available. Eccentric stretching exercises should be integral components of physiotherapy and can achieve a 40% reduction in pain. Extracorporeal shock wave therapy has been shown to reduce pain by 60% with a patient satisfaction of 80%. Due to the limited evidence, injections with platelet-rich plasma (PRP), dextrose (prolotherapy) or polidocanol (sclerotherapy) cannot currently be recommended. Operative therapy is indicated after 6 months of unsuccessful conservative therapy. Open debridement allows all pathologies to be addressed, including osseous abnormalities and intratendinous necrosis. The success rate of over 70% is contrasted by complication rates of up to 40%. The Achilles tendon should be reattached, if detached by >50%. No valid data are available for the transfer of the tendon of the flexor hallucis longus (FHL) muscle but it is frequently applied in cases of more than 50% debridement of the diameter of the Achilles tendon. Lengthening of the gastrocnemius muscle cannot be recommended because insufficient data are available. Tendoscopy is a promising treatment option for isolated retrocalcaneal bursitis and has shown similar success rates to open debridement with significantly lower complication rates.

Basophils Trigger Fibroblast Activation in Cardiac Allograft Fibrosis Development.

Fibrosis is a major component of chronic cardiac allograft rejection. Although several cell types are able to produce collagen, resident (donor-derived) fibroblasts are mainly responsible for excessive production of extracellular matrix proteins. It is currently unclear which cells regulate production of connective tissue elements in allograft fibrosis and how basophils, as potential producers of profibrotic cytokines, are involved this process. We studied this question in a fully MHC-mismatched model of heart transplantation with transient depletion of CD4(+) T cells to largely prevent acute rejection. The model is characterized by myocardial infiltration of leukocytes and development of interstitial fibrosis and allograft vasculopathy. Using depletion of basophils, IL-4-deficient recipients and IL-4 receptor-deficient grafts, we showed that basophils and IL-4 play crucial roles in activation of fibroblasts and development of fibrotic organ remodeling. In the absence of CD4(+) T cells, basophils are the predominant source of IL-4 in the graft and contribute to expansion of myofibroblasts, interstitial deposition of collagen and development of allograft vasculopathy. Our results indicated that basophils trigger the production of various connective tissue elements by myofibroblasts. Basophil-derived IL-4 may be an attractive target for treatment of chronic allograft rejection.

Minimally invasive screw fixation of fractures in the thoracic spine: CT-controlled pre-surgical guidewire implantation in routine clinical practice.

AIM: To evaluate the feasibility and accuracy of minimally invasive, transpedicular screw placement in cervicothoracic fractures with the help of computed tomography (CT)-controlled guidewires. MATERIALS AND METHODS: Two hundred and ninety-three guidewires were inserted in 35 patients (42.9±21.2 years) under CT fluoroscopy (286 thoracic, seven cervical). There were 28 traumatic cases, three pathological fractures, three fractures due to infectious infiltrations, and one osteoporotic fracture. In 151 pedicles, screw placement was performed in the CT room. CT images were reviewed regarding accuracy and cortical violations using the popular 2 mm increment deviation classification of Gertzbein and Robbins. RESULTS: Guidewire implantation resulted in only 28 cortical contacts. Minor encroachments of the pedicle wall by inserted screws occurred in 39.1% (59 of 151) and in 23.8% if taking unavoidable encroachments into account (30 of 59). Pedicular isthmus width correlated to cortical guidewire contacts (r=-0.449; p=0.077) and pedicle violations (all graded "A") by the inserted screws (r=-0.581; p=0.049). Total procedural duration was 138.6±44.2 minutes, representing 14.5±11.6 minutes for each pedicle, while showing a significant correlation against higher vertebral levels (r=-0.849; p=0.0002) and the occurrence of pedicle violations (r=-0.641; p=0.027). CONCLUSIONS: The treatment of vertebral fractures with a guidewire-based pedicle screw insertion technique under CT imaging results in very high accuracy and a low complication rate.

Developmental Changes in Skin Barrier and Structure during the First 5 Years of Life.

The structure of the stratum corneum (SC) and the corresponding skin barrier develops from before birth up to about 4 years of age. Large subject-to-subject variability within an age group requires a large population to observe trends in skin barrier properties over time. Barrier function, quantified by transepidermal water loss (TEWL) and SC thickness, was measured on the upper inner arm and dorsal forearm in subjects aged 3 months to 4 years (n = 171) and a subset of mothers (n = 44). The rate of skin surface area expansion as a function of age peaked before birth (∼90 cm2/week) and declined to a steady plateau (∼10 cm2/week) by 1 year of age. SC thickness increased and TEWL decreased, but did not reach adult values until 3-4 years of age. A better understanding of how skin hydration changes after birth suggests that barrier function may be related mechanistically to skin surface area expansion.

In vitro assessment of skin irritation potential of surfactant-based formulations by using a 3-D skin reconstructed tissue model and cytokine response.

The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing.

Recovery of arctic tundra from thermal erosion disturbance is constrained by nutrient accumulation: a modeling analysis.

Abstract. We calibrated the Multiple Element Limitation (MEL) model to Alaskan arctic tundra to simulate recovery of thermal erosion features (TEFs) caused by permafrost thaw and mass wasting. TEFs could significantly alter regional carbon (C) and nutrient budgets because permafrost soils contain large stocks of soil organic matter (SOM) and TEFs are expected to become more frequent as the climate warms. We simulated recovery following TEF stabilization and did not address initial, short-term losses of C and nutrients during TEF formation. To capture the variability among and within TEFs, we modeled a range of post-stabilization conditions by varying the initial size of SOM stocks and nutrient supply rates. Simulations indicate that nitrogen (N) losses after the TEF stabilizes are small, but phosphorus (P) losses continue. Vegetation biomass recovered 90% of its undisturbed C, N, and P stocks in 100 years using nutrients mineralized from SOM. Because of low litter inputs but continued decomposition, younger SOM continued to be lost for 10 years after the TEF began to recover, but recovered to about 84% of its undisturbed amount in 100 years. The older recalcitrant SOM in mineral soil continued to be lost throughout the 100-year simulation. Simulations suggest that biomass recovery depended on the amount of SOM remaining after disturbance. Recovery was initially limited by the photosynthetic capacity of vegetation but became co-limited by N and P once a plant canopy developed. Biomass and SOM recovery was enhanced by increasing nutrient supplies, but the magnitude, source, and controls on these supplies are poorly understood. Faster mineralization of nutrients from SOM (e.g., by warming) enhanced vegetation recovery but delayed recovery of SOM. Taken together, these results suggest that although vegetation and surface SOM on TEFs recovered quickly (25 and 100 years, respectively), the recovery of deep, mineral soil SOM took centuries and represented a major ecosystem C loss.

Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study.

BACKGROUND: Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa. METHODS: Tissue microarrays composed of tumour samples from 2801 patients in the Ovarian Tumour Tissue Analysis (OTTA) consortium were assessed for FOLR1 expression by centralised immunohistochemistry. We estimated associations for overall (OS) and progression-free (PFS) survival using adjusted Cox regression models. High-grade serous ovarian carcinomas (HGSC) from The Cancer Genome Atlas (TCGA) were evaluated independently for association between FOLR1 mRNA upregulation and survival. RESULTS: FOLR1 expression ranged from 76% in HGSC to 11% in mucinous carcinomas in OTTA. For HGSC, the association between FOLR1 expression and OS changed significantly during the years following diagnosis in OTTA (Pinteraction=0.01, N=1422) and TCGA (Pinteraction=0.01, N=485). In OTTA, particularly for FIGO stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20-0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10-3.25, N=259). In TCGA, FOLR1 mRNA upregulation in HGSC was also associated with increased OS during the first 2 years following diagnosis irrespective of tumour stage (HR: 0.48, 95% CI: 0.25-0.94). CONCLUSIONS: FOLR1-positive HGSC tumours were associated with an increased OS in the first 2 years following diagnosis. Patients with FOLR1-negative, poor prognosis HGSC would be unlikely to benefit from anti-FOLR1 therapies. In contrast, a decreased PFS interval was observed for FOLR1-positive CCC. The clinical efficacy of FOLR1-targeted interventions should therefore be evaluated according to histology, stage and time following diagnosis.

MR-guided laser-induced thermotherapy (LITT) in patients with liver metastases of uveal melanoma.

PURPOSE: Evaluation of the local tumour control rate and survival data for magnetic resonance (MR) imaging-guided laser ablation of uveal malignant melanoma liver metastases by using laser-induced interstitial thermotherapy (LITT). MATERIALS AND METHODS: The LITT was performed in 18 patients with liver metastases (n = 44) from uveal malignant melanoma. All patients tolerated this intervention well. With the Kaplan-Meier method, the survival rates were calculated. Indications for the procedure were defined for patients with no more than five metastases, none of which were larger than 5 cm in diameter: The Indication for LITT treatment were recurrent liver metastases after partial liver resection (22%), locally non-resectable tumours (17%) or metastases in both liver lobes (61%). RESULTS: The mean survival rate for all treated patients was 3.6 years (95% CI: 2.19, 5.06). We started the calculation on the date of diagnosis of the metastases treated with LITT. The median survival was 1.83 years; 1-year survival, 88%; 3-year survival 47%, 5-year survival 17%. Calculated after the first LITT treatment the median survival was 2.8 years (95% CI: 1.0, 5.0). 10 patients were treated by transarterial chemoembolization before LITT. CONCLUSION: MR-guided LITT treatment shows a high local tumour control and survival rates in patients with liver metastases of uveal malignant melanoma.

Inhibition of innate co-receptor TREM-1 signaling reduces CD4(+) T cell activation and prolongs cardiac allograft survival.

The innate receptor "triggering-receptor-expressed-on-myeloid-cells-1" (TREM-1) enhances downstream signaling of "pattern recognition receptor" (PRR) molecules implicated in inflammatory responses. However the mechanistic role of TREM-1 in chronic heart rejection has yet to be elucidated. We examined the effect of TREM-1(+) antigen-presenting cells (APC) on alloreactive CD4(+) lymphocytes. Bm12 donor hearts were transplanted into wild-type MHC-class-II-mismatched C57BL/6J recipient mice. Progressive allograft rejection of bm12-donor hearts with decreased organ function, severe vasculopathy and allograft fibrosis was evident within 4 weeks. TREM-1(+) CD11b(+) MHC-II(+) F4/80(+) CCR2(+) APC and IFNγ-producing CD4(+) cells were detected during chronic rejection. Peptide inhibition of TREM-1 attenuated graft vasculopathy, reduced graft-infiltrating leukocytes and prolonged allograft survival, while being accompanied by sustained low levels of CD4(+) and CD8(+) cell infiltration. Remarkably, temporary inhibition of TREM-1 during early immune activation was sufficient for long-term allograft survival. Mechanistically, TREM-1 inhibition leads to reduced differentiation and proliferation of IFNγ-producing Th1 cells. In conclusion, TREM-1 influences chronic heart rejection by regulating the infiltration and differentiation of CD4(+) lymphocytes.

A direct test of nitrogen and phosphorus limitation to net primary productivity in a lowland tropical wet forest.

Experimental evidence for limitation of net primary productivity (NPP) by nitrogen (N) or phosphorus (P) in lowland tropical forests is rare, and the results from the few existing studies have been inconclusive. To directly test if N or P limit NPP in a lowland tropical wet forest in Costa Rica, we conducted a full factorial fertilization experiment (4 treatments x 6 replicates in 30 x 30 m plots). We focused on the influence of tree size and taxa on nutrient limitation, because in these forests a wide variety of tree functional traits related to nutrient acquisition and use are likely to regulate biogeochemical processes. After 2.7 years, a higher percentage of trees per plot increased basal area (BA) with P additions (66.45% +/- 3.28% without P vs. 76.88% +/- 3.28% with P), but there were no other community-level responses to N or P additions on BA increase, litterfall productivity, or root growth. Phosphorus additions resulted in doubled stem growth rates in small trees (5-10 cm diameter at breast height (dbh); [P < or = 0.01]) but had no effect on intermediate (10-30 cm dbh) or large trees (> 30 cm dbh). Phosphorus additions also increased the percentage of seedling survival from 59% to 78% (P < 0.01), as well as the percentage of seedlings that grew (P = 0.03), and increased leaf number (P = 0.02). Trees from Pentaclethra macroloba, the most abundant species, did not increase growth rates with fertilization (P = 0.40). In contrast, the most abundant palms (Socratea exorrhiza) had more than two times higher stem growth rates with P additions (P = 0.01). Our experiment reiterates that P availability is a significant driver of plant processes in these systems, but highlights the importance of considering different aspects of the plant community when making predictions concerning nutrient limitation. We postulate that in diverse, lowland tropical forests "heterogeneous nutrient limitation" occurs, not only driven by variability in nutrient responses among taxa, but also among size classes and potential functional groups. Heterogeneous responses to nutrient additions could lead to changes in forest structure or even diversity in the long-term, affecting rates of NPP and thus carbon cycling.

Mice lacking both subunits of lysosomal beta-hexosaminidase display gangliosidosis and mucopolysaccharidosis.

The GM2 gangliosidoses, Tay-Sachs and Sandhoff diseases, are caused by mutations in the HEXA (alpha-subunit) and HEXB (beta-subunit) genes, respectively. Each gene encodes a subunit for the heterodimeric lysosomal enzyme, beta-hexosaminidase A (alpha beta), as well as for the homodimers beta-hexosaminidase B (beta beta) and S (alpha alpha). In this study, we have produced mice that have both Hexa and Hexb genes disrupted through interbreeding Tay-Sachs (Hexa-/-) and Sandhoff (Hexb-/-) disease model mice. Lacking both the alpha and beta-subunits these 'double knockout' mice displayed a total deficiency of all forms of lysosomal beta-hexosaminidase including the small amount of beta-hexosaminidase S present in the Sandhoff disease model mice. More surprisingly, these mice showed the phenotypic, pathologic and biochemical features of the mucopolysaccharidoses, lysosomal storage diseases caused by the accumulation of glycosaminoglycans. The mucopolysaccharidosis phenotype is not seen in the Tay-Sachs or Sandhoff disease model mice or in the corresponding human patients. This result demonstrates that glycosaminoglycans are crucial substrates for beta-hexosaminidase and that their lack of storage in Tay-Sachs and Sandhoff diseases is due to functional redundancy in the beta-hexosaminidase enzyme system.

[TEAM®-G (Trauma Evaluation and Management Germany). Serves as a basis for an interdisciplinary training in the emergency room]. / TEAM®-G ("Trauma Evaluation and Management Germany"). Grundlage für ein interdisziplinäres und interprofessionelles Schockraumtraining.

BACKGROUND: The implementation of ATLS® in the daily routine of trauma management in the emergency department is a challenge. This goal cannot be reached by educating ATLS® to a few team members only. In order to enforce the implementation of ATLS® in a level I trauma centre, a generic in-house training was introduced in 2009 with inter-professional integration of all specialists of the trauma team. MATERIALS AND METHODS: The TEAM® course (trauma evaluation and management concept of the American College of Surgeons) was the theoretical basis of the training. This educational program was developed for medical students and multidisciplinary team members. Prior training, a questionnaire for self-assessment was completed by n=84 team members to assess their knowledge about ATLS® principles. The hands-on training time was 90 min. N=10 members of the trauma team worked out three scenarios of multiple injured patients. These were provided as near-reality manikin simulations by a specialist trainer. After the training participants re-evaluated and analysed improvement by the training. Duration of trauma management and the number of missed injuries were analysed one year prior and one year after the training and served as a marker of the process and outcome quality of trauma care. RESULTS: Prior the training, 57% of trainees specified their knowledge related to the ATLS® can be improved. Their expectations were generally satisfied by the training. The mean time of trauma management in the ED could not be reduced one year after the training (36±16 min) compared to one year prior the training (39±18 min), however, the detection of missed injuries (5.6% vs. 3.2%, p<0.05) was significantly diminished after the training. CONCLUSION: Apart form education of ATLS® providers the inauguration of an interdisciplinary and interprofessionel team training may enhance implementation of ATLS- algorithms into daily routine.

Repeated transarterial chemoembolisation using different chemotherapeutic drug combinations followed by MR-guided laser-induced thermotherapy in patients with liver metastases of colorectal carcinoma.

BACKGROUND: To evaluate a treatment protocol with repeated transarterial-chemoembolisation (TACE) downsizing before MR-guided laser-induced interstitial thermotherapy (LITT) using different chemotherapeutic combinations in patients with unresectable colorectal cancer (CRC) liver metastases. METHODS: Two hundred and twenty-four patients were included in the current study. Transarterial-chemoembolisation (mean 3.4 sessions per patient) was performed as a downsizing treatment to meet the LITT requirements (number5, diameter <5 cm). The intra-arterial protocol consisted of either Irinotecan and Mitomycin (n=77), Gemcitabine and Mitomycin (n=49) or Mitomycin alone (n=98) in addition to Lipiodol and Embocept in all patients. Post TACE, all patients underwent LITT (mean 2.2 sessions per patient). RESULTS: Overall, TACE resulted in a mean reduction in diameter of the target lesions of 21.4%. The median time to progression was 8 months, calculated from the start of therapy and the median local tumour control rate was 7.5 months, calculated as of therapy completion. Median survival of patients calculated from the beginning of TACE was 23 months (range 4-110 months), in patients treated with Irinotecan and Mitomycin the median was 22.5 months, Gemcitabine and Mitomycin 23 months and Mitomycin only 24 months with a statistically significant difference between the groups (P<0.01). CONCLUSION: Repeated TACE offers adequate downsizing of CRC liver metastases to allow further treatment with LITT. The combined treatment illustrates substantial survival rates and high local tumour control with statistically significant differences between the three protocols used. Further randomised trials addressing the current study results are required.