Resumption of ovulation in anovulatory women with PCOS and obesity is associated with reduction of 11ß-hydroxyandrostenedione concentrations.

STUDY QUESTION: Is resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity associated with differential changes in endocrine and metabolic parameters (weight, insulin resistance, anti-Müllerian hormone (AMH), and androgens) compared to women with PCOS who remained anovulatory? SUMMARY ANSWER: Resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity is associated with changes in serum 11ß-hydroxyandrostenedione (11OHA4) concentrations. WHAT IS KNOWN ALREADY: Lifestyle interventions have been shown to reduce clinical and biochemical hyperandrogenism in women with PCOS. Weight loss of 5-10% may reverse anovulatory status, thereby increasing natural conception rates. However, the mechanisms underlying why some women with PCOS remain anovulatory and others resume ovulation after weight loss are unclear. Reproductive characteristics at baseline and a greater degree of change in endocrine and metabolic features with lifestyle intervention may be crucial for ovulatory response. STUDY DESIGN, SIZE, DURATION: We used data and samples originating from an earlier randomized controlled trial (RCT), which examined the efficacy of a 6-month lifestyle intervention prior to infertility treatment compared to prompt infertility treatment on live birth rate in women with obesity. A total of 577 women with obesity (BMI > 29 kg/m2) were randomized between 2009 and 2012. Anovulatory women with PCOS who were allocated to the intervention arm of the original RCT (n = 95) were included in the current analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: We defined women as having resumed ovulation (RO+) based on the following criteria: spontaneous pregnancy; or assignment to expectant management; or IUI in natural cycles as the treatment strategy after lifestyle intervention. Steroid hormones were measured using liquid chromatography tandem mass spectrometry. Generalized estimating equations with adjustment for baseline measures and interaction between group and time was used to examine differences in changes of endocrine and metabolic parameters between RO+ (n = 34) and persistently anovulatory women (RO-, n = 61) at 3 and 6 months after intervention. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, the mean ± SD age was 27.5 ± 3.6 years in the RO+ group and 27.9 ± 4.1 years in the RO- group (P = 0.65), and the mean ± SD weights were 101.2 ± 9.5 kg and 105.0 ± 14.6 kg, respectively (P = 0.13). Baseline AMH concentrations showed significant differences between RO+ and RO- women (median and interquartile range [IQR] 4.7 [3.2; 8.3] versus 7.2 [5.3; 10.8] ng/ml, respectively). Baseline androgen concentrations did not differ between the two groups. During and after lifestyle intervention, both groups showed weight loss; changes in 11OHA4 were significantly different between the RO+ and RO groups (P-value for interaction = 0.03). There was a similar trend for SHBG (interaction P-value = 0.07), and DHEA-S (interaction P-value = 0.06), with the most pronounced differences observed in the first 3 months. Other parameters, such as AMH and FAI, decreased over time but with no difference between the groups. LIMITATIONS, REASONS FOR CAUTION: No high-resolution transvaginal ultrasonography was used to confirm ovulatory status at the end of the lifestyle program. The small sample size may limit the robustness of the results. WIDER IMPLICATIONS OF THE FINDINGS: Reduction of androgen concentrations during and after lifestyle intervention is associated with recovery of ovulatory cycles. If our results are confirmed in other studies, androgen concentrations could be monitored during lifestyle intervention to provide individualized recommendations on the timing of resumption of ovulation in anovulatory women with PCOS and obesity. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). The Department of Obstetrics and Gynecology of the UMCG received an unrestricted educational grant from Ferring Pharmaceuticals BV, The Netherlands. A.H. reports consultancy for the development and implementation of a lifestyle App MyFertiCoach developed by Ferring Pharmaceutical Company. All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: The LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530).

Indocyanine green fluorescence in robot-assisted minimally invasive esophagectomy with intrathoracic anastomosis: a prospective study.

Indocyanine green fluorescence angiography (ICG-FA) allows for real-time intraoperative assessment of the perfusion of the gastric conduit during esophagectomy. The aim of this study was to investigate the effect of the implementation of ICG-FA during robot-assisted minimally invasive esophagectomy (RAMIE) with an intrathoracic anastomosis. In this prospective cohort study, a standardized protocol for ICG-FA was implemented in a high-volume center in December 2018. All consecutive patients who underwent RAMIE with an intrathoracic anastomosis were included. The primary outcome was whether the initial chosen site for the anastomosis on the gastric conduit was changed based on ICG-FA findings. In addition, ICG-FA was quantified based on the procedural videos. Out of the 63 included patients, the planned location of the anastomosis was changed in 9 (14%) patients, based on ICG-FA. The median time to maximum intensity at the base of the gastric conduit was shorter (25 s; range 13-49) compared to tip (34 s; range 12-83). In patients with anastomotic leakage, the median time to reach the FImax at the tip was 56 s (range 30-83) compared to 34 s (range 12-66) in patients without anastomotic leakage (p = 0.320). The use of ICG-FA resulted in an adaptation of the anastomotic site in nine (14%) patients during RAMIE with intrathoracic anastomosis. The quantification of ICG-FA showed that the gastric conduit reaches it maximum intensity in a base-to-tip direction. Perfusion of the entire gastric conduit was worse for patients with anastomotic leakage, although not statistically different.

Chronic frames of social inequality: How mainstream media frame race, gender, and wealth inequality.

How social inequality is described­as advantage or disadvantage­critically shapes individuals' responses to it [e.g., B. S. Lowery, R. M. Chow, J. R. Crosby, J. Exp. Soc. Psychol. 45, 375­378, 2009]. As such, it is important to document how people, in fact, choose to describe inequality. In a corpus of 18,349 newspaper articles (study 1), in 764 hand-coded news media publications (study 2), and in a preregistered experiment of 566 lay participants (study 3), we document the presence of chronic frames of race, gender, and wealth inequality. Specifically, race and gender inequalities are more likely to be framed as subordinate groups' disadvantages than as dominant groups' advantages, and wealth inequality is more likely to be described with no frame (followed by dominant group advantage, then subordinate group disadvantage). Supplemental lexicon-based text analyses in studies 1 and 2, survey results in study 3, and a preregistered experiment (study 4; N = 578) provide evidence that the differences in chronic frames are related to the perceived legitimacy of the inequality, with race and gender inequalities perceived as less legitimate than wealth inequality. The presence of such chronic frames and their association with perceived legitimacy may be mechanisms underlying the systematic inattention to White individuals' and men's advantages, and the disadvantages of the working class.

The economic burden of the postoperative management in surgically treated trauma patients with peri- and/or intra-articular fractures of the lower extremities: A prospective multicenter cohort study.

OBJECTIVES: To estimate the economic burden expressed in costs and quality of life of the post-surgical treatment of peri­ and/or intra-articular fractures in the lower extremity from a societal perspective. DESIGN: This is a quantitative study as it aims to find averages and generalize results to wider populations. The design is a cost-of-illness and quality of life study focusing on costs (in euros), Activities of Daily Living (ADL) and Quality of Life (Qol) in patients with peri­ and/or intra-articular fractures of the lower extremities. SETTING: Surgically treated trauma patients with peri­ and/or intra-articular fractures of the lower extremities during 26 weeks follow-up. Patients were included from 4 hospitals in the Netherlands. MAIN OUTCOME MEASURES: Costs, ADL and Quality Adjusted Life Years (QALY). METHODS: Cost of illness was estimated through a bottom-up method. The Dutch Eq-5D-5 L questionnaire was used to calculate utilities while Lower Extremity Functional Scale (LEFS) scores were used as a measure of ADL. Non-parametric bootstrapping was used to test for statistical differences in costs. Subgroup analyses were performed to determine the influence of work status and further sensitivity analyses were performed to test the robustness of the results. RESULTS: Total average societal costs were € 9836.96 over six months. Unexpectedly, total societal and healthcare costs were lower for patients with a paid job relative to patients without. Sensitivity analyses showed that our choice of a societal perspective and the EuroQol as our primary utility measurement tool had a significant effect on the outcomes. The ADL at baseline was respectively; 10.4 and at 26 weeks post-surgery treatment 49.5. The QoL was at baseline respectively; 0.3 and at 26 weeks post-surgery treatment 0.7. These findings are indicative of a significantly improved ADL and QoL (p ≤ 0.05) over time. CONCLUSIONS: This study reveal a substantial economic burden in monetary terms and effect on QoL of patients with peri­ and/or intra-articular fractures of the lower extremities during 26 weeks follow-up. REGISTRATION: This study was registered in the Dutch Trial Register (NTR6077). Date of registration: 01-09-2016.

Locking plate constructs in subtrochanteric fixation: a biomechanical comparison of LCP screws and AO-nuts.

OBJECTIVES: Various studies have reported the use of the 95-degree condylar blade plate in the treatment of a subtrochanteric fracture or non-union. However, the holding power of standard screws in the metaphyseal and diaphyseal area is often diminished due to osteopenia. The alternative in this area is the use of locking plates, Schühlis or AO-nuts. With the latter two, non-locking screws in the blade plate can be converted to a fixed angle fixation. The objective of this study was to compare the stiffness and strength of the AO-nut augmented 95-degree condylar blade plate construct with that of a locking plate construct. In addition, a clinical series of eight patients treated with the AO-nut augmented 95-degree condylar blade plate construct is presented. METHODS: Single screw-plate constructs of a 5.0 mm locking screw/locking compression plate (LCP) and a 4.5 mm non-locking screw/4.5 mm dynamic compression plate (DCP), converted to a fixed-angle screw construct using AO-nuts, were tested by cantilever bending. During loading, force and displacement were recorded, from which the bending stiffness (N/mm) and the yield strength (N) were determined. Secondarily, all patients that underwent surgical treatment for subtrochanteric fracture, malunion or non-union by the senior author using this technique, underwent chart review. RESULTS: The stiffness of the locking screws was about four times higher compared to the AO-nut augmented construct. The yield strength was 2.3 times higher for the locking screw construct. In none of the eight patients treated with the fixed-angle blade plate, failure of the AO-nut augmented construct occurred. CONCLUSIONS: Although the stiffness and strength of the AO-nut augmented construct is less than of the locking screw, excellent clinical outcomes can be achieved utilizing this construct.

Correction to: Routine versus on demand removal of the syndesmotic screw; a protocol for an international randomised controlled trial (RODEO-trial).

An amendment to this paper has been published and can be accessed via the original article.

Edge-Dependent Topology in Kekulé Lattices.

The boundary states of topological insulators are thought not to depend on the precise atomic structure of the boundary. A recent theoretical study showed that, for topological crystalline insulators with given bond strengths, topological states should only emerge for certain edge geometries. We experimentally probe this effect by creating artificial Kekulé lattices with different atomically well-defined edge geometries and hopping ratios in a scanning tunneling microscope. Topological edge modes are found to only appear for specific combinations of edge geometry and hopping ratio.

Resection of hepatic and pulmonary metastasis from metastatic esophageal and gastric cancer: a nationwide study.

The standard of care for gastroesophageal cancer patients with hepatic or pulmonary metastases is best supportive care or palliative chemotherapy. Occasionally, patients can be selected for curative treatment instead. This study aimed to evaluate patients who underwent a resection of hepatic or pulmonary metastasis with curative intent. The Dutch national registry for histo- and cytopathology was used to identify these patients. Data were retrieved from the individual patient files. Kaplan-Meier survival analysis was performed. Between 1991 and 2016, 32,057 patients received a gastrectomy or esophagectomy for gastroesophageal cancer in the Netherlands. Of these patients, 34 selected patients received a resection of hepatic metastasis (n = 19) or pulmonary metastasis (n = 15) in 21 different hospitals. Only 4 patients received neoadjuvant therapy before metastasectomy. The majority of patients had solitary, metachronous metastases. After metastasectomy, grade 3 (Clavien-Dindo) complications occurred in 7 patients and mortality in 1 patient. After resection of hepatic metastases, the median potential follow-up time was 54 months. Median overall survival (OS) was 28 months and the 1-, 3-, and 5- year OS was 84%, 41%, and 31%, respectively. After pulmonary metastases resection, the median potential follow-up time was 80 months. The median OS was not reached and the 1-, 3-, and 5- year OS was 67%, 53%, and 53%, respectively. In selected patients with gastroesophageal cancer with hepatic or pulmonary metastases, metastasectomy was performed with limited morbidity and mortality and offered a 5-year OS of 31-53%. Further prospective studies are required.

Management of resectable esophageal and gastric (mixed adeno)neuroendocrine carcinoma: A nationwide cohort study.

INTRODUCTION: The aim of this study is to provide insight in accuracy of diagnosing, current treatment and survival in patients with resectable esophageal and gastric neuroendocrine- and mixed adenoneuroendocrine carcinomas (NEC, MANEC). METHODS: All patients with esophageal or gastric (MA)NEC, who underwent surgical resection between 2006 and 2016, were identified from the Dutch national registry for histo- and cytopathology (PALGA). Patients with a neuroendocrine tumor lower than grade 3 were excluded. Data on patients, treatment and outcomes were retrieved from the patient records. Diagnosis by endoscopic biopsy was compared with diagnosis by resection specimen. Kaplan Meier survival analysis was performed. RESULTS: A total of 49 patients were identified in 25 hospitals, including 21 patients with esophageal (MA)NEC and 26 patients with gastric (MA)NEC on resection specimen. Biopsy diagnosis of (MA)NEC was correct in 23/27 patients. However, 20/47 patients with definitive diagnosis of (MA)NEC, were misdiagnosed on biopsy. Neoadjuvant therapy was administered in 13 (62%) esophageal (MA)NECs and 12 (46%) gastric (MA)NECs. Survival curves were similar with and without neoadjuvant therapy. One (4.8%) esophageal (MA)NEC and 4 (15%) gastric (MA)NECs died within 90 days postoperatively. For esophageal (MA)NEC the median overall survival (OS) after surgery was 37 months and 1-, 3- and 5-year OS were 71%, 50% and 35%, respectively. For gastric (MA)NEC, the median OS was 23 months and 1-, 3- and 5-year OS were 62%, 50% and 39%, respectively. CONCLUSION: Localized esophageal and gastric (MA)NEC are often misdiagnosed on endoscopic biopsies. After resection, long-term survival was achieved in respectively 35% and 39% of patients.

Routine versus on demand removal of the syndesmotic screw; a protocol for an international randomised controlled trial (RODEO-trial).

BACKGROUND: Syndesmotic injuries are common and their incidence is rising. In case of surgical fixation of the syndesmosis a metal syndesmotic screw is used most often. It is however unclear whether this screw needs to be removed routinely after the syndesmosis has healed. Traditionally the screw is removed after six to 12 weeks as it is thought to hamper ankle functional and to be a source of pain. Some studies however suggest this is only the case in a minority of patients. We therefore aim to investigate the effect of retaining the syndesmotic screw on functional outcome. DESIGN: This is a pragmatic international multicentre randomised controlled trial in patients with an acute syndesmotic injury for which a metallic syndesmotic screw was placed. Patients will be randomised to either routine removal of the syndesmotic screw or removal on demand. Primary outcome is functional recovery at 12 months measured with the Olerud-Molander Score. Secondary outcomes are quality of life, pain and costs. In total 194 patients will be needed to demonstrate non-inferiority between the two interventions at 80% power and a significance level of 0.025 including 15% loss to follow-up. DISCUSSION: If removal on demand of the syndesmotic screw is non-inferior to routine removal in terms of functional outcome, this will offer a strong argument to adopt this as standard practice of care. This means that patients will not have to undergo a secondary procedure, leading to less complications and subsequent lower costs. TRIAL REGISTRATION: This study was registered at the Netherlands Trial Register (NTR5965), Clinicaltrials.gov ( NCT02896998 ) on July 15th 2016.

Predicting suitability of intramedullary fixation for displaced midshaft clavicle fractures.

PURPOSE: Implant-related irritation is a technique-specific complication seen in a substantial number of patients treated with intramedullary nailing for clavicle fractures. The purpose of this study was to identify predictors for developing implant-related irritation in patients with displaced midshaft clavicle fractures treated with elastic stable intramedullary nailing. METHODS: A retrospective analysis of the surgical database in two level 2 trauma centers was performed. Patients who underwent intramedullary nailing for displaced midshaft clavicle fractures between 2005 and 2012 in the first hospital were included. Age, gender, fracture comminution and fracture location were assessed as possible predictors for developing irritation using multivariate logistic regression analysis. These predictors were externally validated using data of patients treated in another hospital. RESULTS: Eighty-one patients were included in initial analysis. In the multivariate analysis, comminuted fractures in comparison to non-comminuted fractures (72 vs. 38%, p = 0.027) and fracture location (p < 0.001) were significantly associated with the development of implant-related irritation. In particular, lateral diaphyseal fractures caused irritation compared to fractures on the medial side of the cut-off point (88 vs. 26%). External validation of these predictors in 48 additional patients treated in another hospital showed a similar predictive value of the model and a good fit. CONCLUSION: Comminuted and lateral diaphyseal fractures were found to be statistically significant and independent predictors for developing implant-related irritation. We, therefore, believe that intramedullary nailing might not be suitable for these types of fractures. Future studies are needed to determine whether alternative surgical techniques or implants would be more suitable for these specific types of fractures.

Effect of a titanium cage as a stand-alone device on biomechanical stability in the lumbosacral spine of canine cadavers.

Degenerative lumbosacral stenosis is a common disease in dogs characterised by intervertebral disc herniation, loss of disc height and stenosis. Decompressive dorsal laminectomy and partial discectomy can cause spinal instability and worsen foraminal stenosis. Pedicle screw and rod fixation (PSRF) with an intervertebral body cage allows for distraction and restoration of disc height and restores foraminal apertures. The aim of this study was to evaluate the ex vivo biomechanical properties of a titanium intervertebral cage alone and in combination with PSRF in the lumbosacral spine of dogs. The range of motion, neutral zone, neutral zone stiffness and elastic zone stiffness of the lumbosacral joint (L7-S1) of nine canine cadavers were determined in flexion/extension, lateral bending and axial rotation for four conditions: (1) native (unmodified) spine; (2) dorsal laminectomy and discectomy; (3) stand-alone cage; and (4) cage in combination with PSRF. The intervertebral disc height decreased after dorsal laminectomy, but increased after insertion of the cage. Insertion of the stand-alone cage decreased the range of motion and neutral zone compared to the laminectomy-discectomy and increased neutral zone stiffness in all directions. The range of motion further decreased after PSRF. From a biomechanical point of view, the use of a stand-alone intervertebral cage is a potential alternative to dorsal fixation of the lumbosacral junction, since it increases spinal stability and restores disc height.

The relationship between 63days of 24-h urinary free cortisol and hair cortisol levels in 10 healthy individuals.

BACKGROUND: Interest in measuring cortisol in scalp hair is increasing because of its assumed ability to provide a historical timeline of previous systemic levels of cortisol. Yet, it remains uncertain how well hair cortisol represents the total systemic secretion of cortisol over time. METHODS: Ten healthy individuals collected 24-h urine samples for 63 consecutive days and provided a hair sample at the end of the study period. 24-h urinary creatinine levels in every urine sample were determined to assess completeness of the samples. Cortisol levels in 24-h urine samples and in hair were measured with liquid chromatography tandem mass spectrometry. The correlations between urinary cortisol and hair cortisol were calculated using Kendall's tau. RESULTS: We found a nonsignificant moderate correlation between average urinary cortisol secretion and average hair cortisol concentration rт=0.422, p=0.089. CONCLUSIONS: Hair cortisol concentration correlates low to moderately with 24-h urinary cortisol concentration over a period of 63days.

Translational challenges for the development of a novel nucleus pulposus substitute: Experimental results from biomechanical and in vivo studies.

Nucleus pulposus replacement therapy could offer a less invasive alternative to restore the function of moderately degenerated intervertebral discs than current potentially destructive surgical procedures. Numerous nucleus pulposus substitutes have already been investigated, to assess their applicability for intradiscal use. Still, the current choice of testing methods often does not lead to efficient translation into clinical application. In this paper, we present the evaluation of a novel nucleus pulposus substitute, consisting of a hydromed core and an electrospun envelope. We performed three mechanical evaluations and an in vivo pilot experiment. Initially, the swelling pressure of the implant was assessed in confined compression. Next, we incorporated the implant into mechanically damaged caprine lumbar intervertebral discs to determine biomechanical segment behaviour in bending and torsion. Subsequently, segments were serially tested in native, damaged and repaired conditions under dynamic axial compressive loading regimes in a loaded disc culture system. Finally, nucleus pulposus substitutes were implanted in a live goat spine using a transpedicular approach. In confined compression, nucleus pulposus samples as well as implants showed some load-bearing capacity, but the implant exhibited a much lower absolute pressure. In bending and torsion, we found that the nucleus pulposus substitute could partly restore the mechanical response of the disc. During dynamic axial compression in the loaded disc culture system, on the other hand, the implant was not able to recover axial compressive behaviour towards the healthy situation. Moreover, the nucleus pulposus substitutes did not remain in place in the in vivo situation but migrated out of the disc area. From these results, we conclude that implants may mimic native disc behaviour in simple mechanical tests, yet fail in other, more realistic set-ups. Therefore, we recommend that biomaterials for nucleus pulposus replacement be tested in testing modalities of increasing complexity and in their relevant anatomical surroundings, for a more reliable prediction of clinical potential.

Comparison of two devices for the treatment of keloid scars with the use of intralesional cryotherapy: An experimental study.

BACKGROUND: Intralesional (IL) cryotherapy is a new technique for the treatment of keloid scars, in which the scar is frozen from inside. Two cryodevices are available, which were recently evaluated. Both devices showed promising results, but differed in clinical outcome. To explain these differences, more understanding of the working mechanism of both devices is required. OBJECTIVE: This experimental study was designed to investigate and compare the thermal behavior of an argon gas- and a liquid nitrogen-based device. Thermal behavior constitutes: (1) minimum tissue temperature (°C), (2) the freezing rate (°C/min). The thermal behavior was measured inside and on the outer surface of the scar. Both devices were tested ex vivo and in vivo. RESULTS: Ex vivo, when determining the maximum freezing capacity, the argon gas device showed a higher end temperature compared to the liquid nitrogen device (argon gas: -120°C, liquid nitrogen: -140°C) and a faster freezing rate (argon gas: -1300°C/min, liquid nitrogen: -145°C/min). In vivo, measured inside the keloid, the argon gas device showed a lower end temperature than the liquid nitrogen device (argon gas: -36.4°C, liquid nitrogen: -8.1°C) and a faster freezing rate (argon gas: -14.7°C/min, liquid nitrogen: -5°C/min). The outer surface of the scar reached temperatures below -20°C with both devices as measured with the thermal camera. CONCLUSION: In conclusion, the argon gas device displayed a lower end temperature and a faster freezing rate in vivo compared to the liquid nitrogen device. Although this resulted in lower recurrence rates for the argon gas device, more hypopigmentation was seen compared to the liquid nitrogen device following treatment. Finally, the low outer surface temperatures measured with both devices, suggest that some hypopigmentation following treatment is inevitable.

MRI reveals the in vivo cellular and vascular response to BEZ235 in ovarian cancer xenografts with different PI3-kinase pathway activity.

BACKGROUND: The phosphoinositide-3 kinase (PI3K) pathway is an attractive therapeutic target. However, difficulty in predicting therapeutic response limits the clinical implementation of PI3K inhibitors. This study evaluates the utility of clinically relevant magnetic resonance imaging (MRI) biomarkers for noninvasively assessing the in vivo response to the dual PI3K/mTOR inhibitor BEZ235 in two ovarian cancer models with differential PI3K pathway activity. METHODS: The PI3K signalling activity of TOV-21G and TOV-112D human ovarian cancer cells was investigated in vitro. Cellular and vascular response of the xenografts to BEZ235 treatment (65 mg kg(-1), 3 days) was assessed in vivo using diffusion-weighted (DW) and dynamic contrast-enhanced (DCE)-MRI. Micro-computed tomography was performed to investigate changes in vascular morphology. RESULTS: The TOV-21G cells showed higher PI3K signalling activity than TOV-112D cells in vitro and in vivo. Treated TOV-21G xenografts decreased in volume and DW-MRI revealed an increased water diffusivity that was not found in TOV-112D xenografts. Treatment-induced improvement in vascular functionality was detected with DCE-MRI in both models. Changes in vascular morphology were not found. CONCLUSIONS: Our results suggest that DW- and DCE-MRI can detect cellular and vascular response to PI3K/mTOR inhibition in vivo. However, only DW-MRI could discriminate between a strong and weak response to BEZ235.

Relation between radiological assessment and biomechanical stability of lumbar interbody fusion in a large animal model.

PURPOSE: To relate the progress of vertebral segmental stability after interbody fusion surgery with radiological assessment of spinal fusion. METHODS: Twenty goats received double-level interbody fusion and were followed for a period of 3, 6 and 12 months. After killing, interbody fusion was assessed radiographically by two independent observers. Subsequently, the lumbar spines were subjected to four-point bending and rotational deformation, assessed with an optoelectronic 3D movement registration system. In addition, four caprine lumbar spines were analysed in both the native situation and after the insertion of a cage device, as to mimic the direct post-surgical situation. The range of motion (ROM) in flexion/extension, lateral bending and axial rotation was analysed ex vivo using a multi-segment testing system. RESULTS: Significant reduction in ROM in the operated segments was already achieved with moderate bone ingrowth in flexion/extension (71 % reduction in ROM) and with only limited bone ingrowth in lateral bending (71 % reduction in ROM) compared to the post-surgical situation. The presence of a sentinel sign always resulted in a stable vertebral segment in both flexion/extension and lateral bending. For axial rotation, the ROM was already limited in both native and cage inserted situations, resulting in non-significant differences for all radiographic scores. DISCUSSION: In vivo vertebral segment stability, defined as a significant reduction in ROM, is achieved in an early stage of spinal fusion, well before a radiological bony fusion between the vertebrae can be observed. Therefore, plain radiography underestimates vertebral segment stability.

Comparison of fondaparinux with low molecular weight heparin for venous thromboembolism prevention in patients requiring rigid or semi-rigid immobilization for isolated non-surgical below-knee injury.

BACKGROUND: In several small studies, anticoagulant therapy reduced the incidence of venous thromboembolism (VTE) in patients with isolated lower-limb injuries. OBJECTIVES: To compare the efficacy and safety of fondaparinux 2.5 mg (1.5 mg in patients with a creatinine clearance between 30 and 50 mL min(-1) ) over nadroparin 2850 anti-factor Xa IU. PATIENTS AND METHODS: In this international, multicenter, randomized, open-label study, patients with an isolated non-surgical unilateral below-knee injury having at least one additional major risk factor for VTE and requiring, in the Investigator's opinion, rigid or semi-rigid immobilization for 21-45 days with thromboprophylaxis up to complete mobilization received subcutaneously once-daily either fondaparinux or nadroparin. The primary efficacy outcome was the composite of VTE (symptomatic or ultrasonographically detected asymptomatic deep vein thrombosis of the lower limb or symptomatic pulmonary embolism) and death up to complete mobilization. The main safety outcome was major bleeding. RESULTS: We randomized 1349 patients (mean age 46 years): 88.7% had a bone fracture, and 83.8% had a plaster cast fitted (mean duration of immobilization, 34 days). The primary efficacy outcome occurred in 15 of 584 patients (2.6%) in the fondaparinux group and 48 of 586 patients (8.2%) in the nadroparin group (odds ratio, 0.30; 95% confidence interval [CI], 0.15-0.54; P < 0.001). A single major bleed was experienced by fondaparinux-treated patients and none by nadroparin-treated patients. These results were maintained up to the end of follow-up. CONCLUSIONS: Fondaparinux 2.5 mg day(-1) may be a valuable therapeutic option over nadroparin 2850 anti-FXa IU day(-1) for preventing VTE after below-knee injury requiring prolonged immobilization in patients with additional risk factors.

Understanding transportation-caused rangeland damage in Mongolia.

Mongolia, a vast and sparsely populated semi-arid country, has very little formal road infrastructure. Since the 1990s, private ownership and usage of vehicles has been increasing, which has created a web of dirt track corridors due to the communal land tenure and unobstructed terrain, with some of these corridors reaching over 4 km in width. This practice aids wind- and water-aided erosion and desertification, causing enormous negative environmental effects. Little is being done to counter the phenomenon, mainly because the logic of the driving behaviour that causes this dirt road widening is not fully understood. The research in this article postulates that this driving behaviour has rational foundations and is linked to various geographical factors (natural and man-made geographical features). We analysed 11,000 km of arterial routes in the country using spatial statistics and determined that geographically weighted regression (GWR) analysis offers a good explanation for whether, and by how much, the selected geographical factors affect the creation of corridor widths and how their effect varies across the landscape. We determined that corridor widths are correlated to factors such as proximity to river crossings, traffic intensity, and vegetation abundance. Knowing these factors can help local planners and engineers design counter-measures that could help to control and reduce the widths of these corridors, until paved roads can replace the dirt track corridors.