Status of low-energy accelerator-based BNCT worldwide and in Argentina.

Existing and active low-energy Accelerator-Based BNCT programs worldwide will be reviewed and compared. In particular, the program in Argentina will be discussed which consists of the development of an Electro-Static-Quadrupole (ESQ) Accelerator-Based treatment facility. The facility is conceived to operate with the deuteron-induced reactions 9Be(d,n)10B and 13C(d,n)14N at 1.45 MeV deuteron energy, as neutron sources. Neutron production target development status is specified. The present status of the construction of the new accelerator development laboratory and future BNCT centre is shown.

Zinc and multivitamin supplementation have contrasting effects on infant iron status: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND/OBJECTIVES: Zinc (Zn) supplementation adversely affects iron status in animal and adult human studies, but few trials have included young infants. The objective of this study was to determine the effects of Zn and multivitamin (MV) supplementation on infant hematologic and iron status. SUBJECTS/METHODS: In a double-blind RCT, Tanzanian infants were randomized to daily, oral Zn, MV, Zn and MV or placebo treatment arms at the age of 6 weeks of life. Hemoglobin concentration (Hb) and red blood cell indices were measured at baseline and at 6, 12 and 18 months of age. Plasma samples from 589 infants were examined for iron deficiency (ID) at 6 months. RESULTS: In logistic regression models, Zn treatment was associated with greater odds of ID (odds ratio (OR) 1.8 (95% confidence interval (CI) 1.0-3.3)) and MV treatment was associated with lower odds (OR 0.49 (95% CI 0.3-0.9)). In Cox models, MV was associated with a 28% reduction in risk of severe anemia (hazard ratio (HR)=0.72 (95% CI 0.56-0.94)) and a 26% reduction in the risk of severe microcytic anemia (HR=0.74 (0.56-0.96)) through 18 months. No effects of Zn on risk of anemia were seen. Infants treated with MV alone had higher mean Hb (9.9 g/dl (95% CI 9.7-10.1)) than those given placebo (9.6 g/dl (9.4-9.8)) or Zn alone (9.6 g/dl (9.4-9.7)). CONCLUSIONS: MV treatment improved iron status in infancy, whereas Zn worsened iron status but without an associated increase in risk for anemia. Infants in long-term Zn supplementation programs at risk for ID may benefit from screening and/or the addition of a MV supplement.

Precise localization of silicone-based intercranial planar electrodes in magnetic resonance imaging.

Intercranial planar electrodes enable neural recordings with high spatial resolution in diagnosis as well as for treatments. The value of the measurements increases with the precision of localization of the electrodes related to the individual anatomy. In this context, post-implantation MRI provides excellent soft tissue contrast, but the accurate localization of electrodes is impaired by magnetic susceptibility artifacts. We have addressed this problem without adding a substantial burden to the electrode fabrication process. Simple silicone reference structures were strategically placed on the implant surface to visualize the electrodes position in MRI. These reference structures allowed high precision electrode localization independently of electrode imaging artifacts. This implant manufacturing approach could prove extremely useful in combination with existing image processing pipelines.

Comparison of interfragmentary compression in conventional and locked plating of proximal unicondylar tibia fractures : A biomechanical cadaver study.

The extent of interfragmentary compression in intra-articular fractures treated with various fixation methods have not yet been reported. Lateral split fractures were created in six pairs of cadaver tibiae treated -using buttress plating with lag screws (group C) or locked buttress plating after clamp compression (group L). Interfragmentary compression and fracture displacement were continuously measured using pressure sensors and a stereoscopic 3-D image correlation system. Significantly larger interfragmentary compression was found initially after clamping the fragment (p < 0.05) in group C (median ±â€ˆSD ; 45.1 ±â€ˆ5.0 N/mm2) compared with group L (33.6 ± 3.4 N/mm2), and a statistical trend towards larger compression was also found after cyclic loading (p = 0.05) in group C (45.3 ±â€ˆ8.6 N/mm2) compared with group L (28.7 ±â€ˆ5.8 N/mm2). These data indicate that conventional plating with lag screws achieves higher interfragmentary compression in this model compared with external clamp compression and locked plating.

Present status of accelerator-based BNCT: Focus on developments in Argentina.

In this work we provide some information on the present status of accelerator-based BNCT (AB-BNCT) worldwide and subsequently concentrate on the recent accelerator technology developments in Argentina.

Patient-reported outcome assessment after total joint replacement: comparison of questionnaire completion times on paper and tablet computer.

INTRODUCTION: Patient-reported outcome (PRO) assessment is becoming increasingly important after joint replacement surgery. However, PRO data collection, questionnaire handling, and data processing are time consuming and costly process. The aim of our study was to evaluate the efficiency of PRO assessment using tablet computers compared with traditional paper questionnaires in a total hip or knee arthroplasty (THR or TKR) population. MATERIALS AND METHODS: We recruited 100 patients from outpatient clinics attending for routine follow-up 2 months, 1 year, or 5 years after THR or TKR. Fifty patients completed the Western Ontario and McMaster Universities (WOMAC) osteoarthritis score and Forgotten Joint Score-12 (FJS-12) questionnaires on paper, and 50 patients completed these on a tablet computer. Questionnaire completion was timed for each PRO assessment and for manual data entry of the paper questionnaires into the database. The t test, Mann-Whitney U test, Fisher's exact test, and Wilcoxon test were used for statistical analysis. RESULTS: The mean age of the patients was 67.0 years (standard deviation 10.3 years), with no significant difference between the two groups. Median time for WOMAC questionnaire completion (including data entry for the paper questionnaires) was 197 s for the paper version and 117 s for the tablet version (p < 0.001). Median times for completion of FJS-12 were comparable for paper and tablet versions (32 vs. 37 s). We did not find a significant correlation between age and time for questionnaire completion. CONCLUSION: Electronic PRO data collection can substantially decrease time, logistics, and effort associated with questionnaire completion in daily clinical practice. It is also acceptable for use in an older arthroplasty population.

Mid term results of distal femoral fractures treated with a polyaxial locking plate: a multi-center study.

OBJECTIVE: Locking plates have become a standard implant in the treatment of distal femoral fractures. Newer designs allow polyaxial screw placement as well as the ability to lock the lag screws. METHODS: The consecutive multi-centre study cohort consists of all distal femoral fractures treated with the NCB® Distal Femur plate (Zimmer, Warsaw, USA) and a minimum follow-up of twelve months. Fracture classification according the AO/ OTA system and the trauma mechanism radiological evaluation and complications were documented. Clinical evaluation consisted of the Short Form SF12 questionnaire (SF12), the Hospital for Special Surgery Score (HSS) and clinical assessment of range of motion. RESULTS: Twenty-five patients with twenty-six fractures were available for follow-up with a minimum required follow-up of twelve months. 81% of the fractures were intra-articular. 48% of the patients were multi-traumatised, 38% having open fractures. All except two went to union (92%) with the primary procedure. The HSS Score was 79 (32-99) and the SF 12 (physical and mental) 40 (19-57) and 54 (21-66) at follow-up. There were five patients requiring surgical revision (19%). CONCLUSION: These fractures are often combined with concomitant injuries. Using modern locked implants high union rates can be achieved with a good function and patient satisfaction when respecting biologic and biomechanical principles.

Accelerator-based BNCT.

The activity in accelerator development for accelerator-based BNCT (AB-BNCT) both worldwide and in Argentina is described. Projects in Russia, UK, Italy, Japan, Israel, and Argentina to develop AB-BNCT around different types of accelerators are briefly presented. In particular, the present status and recent progress of the Argentine project will be reviewed. The topics will cover: intense ion sources, accelerator tubes, transport of intense beams, beam diagnostics, the (9)Be(d,n) reaction as a possible neutron source, Beam Shaping Assemblies (BSA), a treatment room, and treatment planning in realistic cases.

Development of a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy.

We describe the present status of an ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based (AB)-BNCT. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction. The machine currently being constructed is a folded TESQ with a high-voltage terminal at 0.6 MV. We report here on the progress achieved in a number of different areas.

Accelerator tube construction and characterization for a tandem-electrostatic-quadrupole for accelerator-based boron neutron capture therapy.

The accelerator tubes are essential components of the accelerator. Their function is to transport and accelerate a very intense proton or deuteron beam through the machine, from the ion source to the neutron production target, without significant losses. In this contribution, we discuss materials selected for the tube construction, the procedures used for their assembly and the testing performed to meet the stringent requirements to which it is subjected.

Nutrition Education to Improve Dietary Intake and Micronutrient Nutriture among Children in Less-Resourced Areas: A Randomised Controlled Intervention in Kabarole District; Western Uganda

Objective: To determine whether nutrition education targeting the child-feeding practices of low-income rural caregivers will reduce anaemia and improve vitamin A nutriture of the young children in their care.Design: A controlled intervention trial; based on experiential learning theory. Forty-six women completed a nine-session nutrition education programme; while controls (n = 43) concurrently engaged in sewing classes. Setting: Two rural farming communities in the Kabarole district; western Uganda. Subjects: Less literate; low-income rural female caregivers and the children in their care (6-48 months). Outcome measures: Caregivers' child-feeding practices and the children's nutritional status were assessed at baseline; one month after intervention (Follow-up 1) and one year from baseline (Follow-up 2). Results: Caregivers in the intervention group reported improved child snacking patterns; food-selection practices; meal adequacy; and food variety. Children in the intervention group recorded lower haemoglobin levels at baseline (9.86 vs. 10.70 g/dl) and caught up with controls at Follow-up 1 (10.06 vs. 10.78 g/dl). However; changes were not sustained. Mean retinol-binding protein improved from 0.68 ?mol/l (95CI: 0.57-0.78) to 0.91 ?mol/l (95CI: 0.78-1.03) among intervention children; but remained approximately the same in controls. Vitamin A nutriture was influenced by infections. Conclusion: Nutrition education significantly improved feeding practices and children's nutritional status. The effectiveness and sustainability of this programme can be enhanced if nutrition education is integrated into other food-production and public health programmes

Nutrition Education to Improve Dietary Intake and Micronutrient Nutriture among Children in Less-Resourced Areas: A Randomised Controlled Intervention in Kabarole District; Western Uganda

Objective:To determine whether nutrition education targeting the child-feeding practices of low-income rural caregivers will reduce anaemia and improve vitamin A nutriture of the young children in their care.Design: A controlled intervention trial; based on experiential learning theory. Forty-six women completed a nine-session nutrition education programme; while controls (n = 43) concurrently engaged in sewing classes. Setting: Two rural farming communities in the Kabarole district; western Uganda. Subjects: Less literate; low-income rural female caregivers and the children in their care (6-48 months). Outcome measures: Caregivers' child-feeding practices and the children's nutritional status were assessed at baseline; one month after intervention (Follow-up 1) and one year from baseline (Follow-up 2). Results: Caregivers in the intervention group reported improved child snacking patterns; food-selection practices; meal adequacy; and food variety. Children in the intervention group recorded lower haemoglobin levels at baseline (9.86 vs. 10.70 g/dl) and caught up with controls at Follow-up 1 (10.06 vs. 10.78 g/dl). However; changes were not sustained. Mean retinol-binding protein improved from 0.68 ?mol/l (95CI: 0.57-0.78) to 0.91 ?mol/l (95CI: 0.78-1.03) among intervention children; but remained approximately the same in controls. Vitamin A nutriture was influenced by infections. Conclusion: Nutrition education significantly improved feeding practices and children's nutritional status. The effectiveness and sustainability of this programme can be enhanced if nutrition education is integrated into other food-production and public health programmes

[Periprosthetic fractures of the knee joint]. / Periprothetische Frakturen am Kniegelenk.

The demographic developments and an increasing number of total knee replacements will lead to more periprosthetic fractures in the future. These fractures can be classified into intraoperative and postoperative. Revisions in particular are associated with a higher incidence of intra-operative fractures, specifically for the tibia and patella. Most fractures occur in the postoperative period with an average of 2-4 years after the primary procedure. Most commonly the femur is involved. The history and clinical examination as well as imaging are crucial for the treatment as loose components would significantly alter the treatment strategy. In this case a revision has to be carefully planned. In the majority of the cases the prosthesis is well fixed especially at the femur. An open reduction internal fixation (ORIF) can then be carried out. A stable situation must be achieved to provide early post-operative mobilization. Also an anatomic reduction should be achieved with correct alignment especially with respect to varus/valgus and rotation. Modern locked implants can provide this with good success also with the possibility of minimally invasive techniques and polyaxial screw positioning. Retrograde intramedullary devices can be a feasible alternative. Similar principles can be used for the tibia whereas the patella can be stabilized with tension band wiring in the case of good bone stock but still remains a problem in case of bad bone stock.

RBP-to-retinol ratio, but not total RBP, is elevated in patients with type 2 diabetes.

AIM: It was recently reported that serum retinol-binding protein (RBP), also known as retinol-binding protein 4 (RBP4), was positively associated with systemic insulin resistance. We hypothesized that an imbalance between RBP and retinol might be the underlying cause for this association. METHODS: We studied the ratio between RBP and retinol in 233 humans divided into groups depending on normal glucose tolerance (NGT), impaired glucose tolerance (IGT), type 2 diabetes (T2DM) and presence or absence of obesity. RESULTS: Plasma RBP and retinol levels were lower in patients with T2DM than in individuals with NGT (p < 0.05 and p < 0.0001 respectively). In contrast, RBP-to-retinol ratio was higher in individuals with T2DM (p < 0.0001) and IGT (p < 0.05). Following multivariate adjustment, RBP and retinol correlated positively with low-density lipoprotein (LDL) and triglycerides (p < 0.0001, except retinol and LDL: p < 0.001). RBP-to-retinol ratio correlated positively with glucose 2 h after an oral glucose tolerance test (p < 0.0001) and with C-reactive protein (p < 0.001). Retinol, RBP and adipose tissue RBP messenger RNA (mRNA) levels shared an inverse relationship with plasma interleukin-6, and adipose tissue RBP mRNA levels correlated positively with plasma tumour necrosis factor-alpha (TNF-alpha) and skeletal muscle TNF-alpha mRNA levels. CONCLUSIONS: Our results suggest that the excess of RBP relative to retinol, assessed as the RBP-to-retinol ratio, is more indicative of T2DM than RBP itself. Hence, the previously reported insulin resistance in mice induced by overexpression or injection of RBP could be because of higher levels of RBP relative to retinol rather than higher total levels of RBP. Moreover, TNF-alpha may have a role in RBP-mediated adipose to muscle crosstalk.

Treatment of periprosthetic femur fractures with the non-contact bridging plate: a new angular stable implant.

OBJECTIVES: We report the application of a new fixed angle plate (NCB DF, Zimmer inc. USA, Warsaw, IN) in the treatment of periprosthetic femur fractures. The NCB DF combines conventional plating technique with polyaxial screw placement and angular stability. DESIGN: Prospective cohort study. SETTING: A single level-1 trauma center. PATIENTS: From May 2003 to December 2005, a total of 24 patients with periprosthetic femur fractures were treated. The NCB DF femur plate was used in all cases. The average follow-up period was 12 months (3-31 months). Twelve patients had a periprosthetic fracture after total knee replacement (TKA) and 12 patients after total hip replacement (THA). The mean period from primary joint replacement to periprosthetic fracture was 8.2 years for the THA group and 7.2 years for the TKA group. INTERVENTION: A combined conventional/locking surgical technique was performed in all the cases. MAIN OUTCOME MEASURES: Union, non-union, mal-union, duration of surgery, range of motion, postoperative mobility, subjective patient satisfaction and complications. RESULTS: The union rate was 90%, the mal-union rate 5% and the re-operation rate 15%. Postoperative mobility reached the preoperative level in all but for two patients. Three complications occurred relating to the implant or the procedure: one fatigue failure of the plate (non-union), one screw breakage, and one wound infection. CONCLUSIONS: The NCB DF combines conventional plating technique with polyaxial screw placement and angular stability. This combination technique shows promising results regarding union and mal-union rates in periprosthetic fractures in elderly and osteoporotic patients.

[The Non-Contact Bridging Plate. A new fixed-angle device for the minimally-invasive treatment of fractures of the proximal humerus--technique and preliminary results]. / Die Non-Contact-Bridging-(NCB-) Platte. Ein neues winkelstabiles System zur minimal-invasiven Versorgung von Frakturen des proximalen Humerus--Technik und erste Ergebnisse.

BACKGROUND: Fractures of the proximal humerus are common in elderly patients, especially in osteoporotic bone. Requirements for surgical treatment are high primary stability to allow early functional physiotherapy. The Non-Contact Bridging (NCB) Plate for the proximal humerus (PH) is a new head locking system for treating fractures of the proximal humerus which allows minimally invasive surgery (MIS). METHODS: In this contribution, the implant and technique are described, as well as the analysis of the first clinical results after 61 procedures. RESULTS: In a mainly elderly patient population (mean: 73 years, range: 50-91 years) 61 minimally-invasive procedures were performed. The placement of screws led to a high primary stability. Primary implant failure occurred in one case (1.69%). The average constant score after 6 months was 62 points (age related mean 72). CONCLUSIONS: Using the MIS-technique, the NCB-PH plate provides high primary stability, allowing functional treatment without postoperative limitations. The first clinical results show a good functional outcome in a mainly elderly patient population.

A comparison of the beta-D-xyloside, odiparcil, to warfarin in a rat model of venous thrombosis.

BACKGROUND: A significant need exists for new chronic oral anticoagulation therapies to replace warfarin. Previous studies have shown that beta-D-xylosides, which prime glycosaminoglycan (GAG) synthesis, have antithrombin and antithrombotic activity. In the following report, a new orally active beta-D-xyloside (odiparcil) has been characterized in a rat model of venous thrombosis and its efficacy and bleeding liability compared to warfarin. Additionally, studies were conducted to investigate odiparcil's ex vivo antithrombin and antiplatelet activity, and also to explore the potential utility of protamine sulfate as a neutralizing agent. METHODS AND RESULTS: In vivo thrombosis studies were conducted in a rat inferior vena cava model, and bleeding studies in a rat tail transection model. Following oral dosing, warfarin and odiparcil produced dose-related suppression of thrombus formation. A therapeutically relevant dose of warfarin in this model (international normalized ratio; INR 3.0) achieved approximately 65% inhibition of thrombus formation. Warfarin caused dose-related significant increases in bleeding indices. Odiparcil antithrombotic activity was limited by its mechanism to a maximum suppression of thrombus formation of 65-70%, and did not prolong bleeding indices. Additionally, odiparcil-induced heparin cofactor II (HCII)-dependent antithrombin activity was shown to be a function of dermatan sulfate-like GAG production. Other than thrombin-related effects, no odiparcil effects on platelet function were observed. In antidote studies, it was demonstrated that odiparcil-induced antithrombotic activity could be partially neutralized by protamine sulfate. CONCLUSIONS: These experiments suggest that an antithrombotic approach based upon xyloside induction of circulating GAGs may have the potential to approximate the efficacy of warfarin and yet with a reduced risk to hemostasis.

P2X1 stimulation promotes thrombin receptor-mediated platelet aggregation.

P2X1 receptors are ATP-gated channel demonstrated to be involved in multiple platelet responses, although in vitro analysis has been complicated by the effects of rapid desensitization. To further investigate potential roles of P2X1 receptors in platelet activation, the current study employed methods which maximally preserved P2X1 functionality. In preliminary in vivo studies, P2X1-deficiency reduced thrombus formation following the laser-induced, but not FeCl3-induced injury. Given the multiple potential mechanisms involved in thrombus formation in vivo, including tissue-factor/thrombin generation pathways, subsequent studies were designed to investigate the effects of P2X1 inhibition or stimulation on platelet activation in vitro; specifically, the interaction of P2X1 with thrombin receptor stimulation. Aggregation initiated by low/threshold levels of a protease-activated receptor (PAR)4 agonist was reduced in P2X1-deficient murine platelets, and inhibition of P2X1 in wild-type platelets similarly reduced PAR4-mediated aggregation. In human platelets, aggregation to low/threshold stimulation of PAR1 was inhibited with the P2X1 antagonist MRS2159. In addition, P2X1 stimulation primed human platelet responses, such that subsequent sub-threshold PAR1 responses were converted into significant aggregation. Selective ADP receptor inhibitors attenuated P2X1-mediated priming, suggesting that the synergy between P2X1 and sub-threshold PAR1 stimulation was in part because of enhanced granular release of ADP. Overall, the present study defines a novel interaction between platelet P2X1 and thrombin receptors, with P2X1 functioning to amplify aggregation responses at low levels of thrombin receptor stimulation.

Potentiation of platelet activation through the stimulation of P2X1 receptors.

The platelet P2X1 purinergic receptor is a ligand-gated ion channel that responds to ATP. The precise role of P2X1 in platelet function is unknown, though stimulation with the P2X1 agonist alpha,beta-Me-ATP is known to result in platelet shape change through elevation of calcium levels. The aim of the present study was to examine further the effects of P2X1 stimulation on platelet activation. Stimulation of P2X1 with alpha,beta-Me-ATP resulted in shape change and small aggregate formation in heparin-anticoagulated platelet preparations. Given the ability of heparin to potentiate platelet activation, subsequent experiments were performed in hirudin. In these platelet preparations, aggregate formation in response to alpha,beta-Me-ATP alone was less than that observed in heparin; however, alpha,beta-Me-ATP significantly potentiated platelet aggregate formation when added in conjunction with other weak platelet agonists [epinephrine or thrombopoietin (TPO)]. Platelet aggregate formation was confirmed by single platelet loss (microaggregate formation), microscopy, and light transmittance studies. Further, the P2X1 antagonist MRS-2159 inhibited platelet shape change and aggregation responses induced by alpha,beta-Me-ATP. Overall, this study demonstrates that P2X1 stimulation can induce/potentiate platelet activation in combination with other platelet agonists. These results are the first demonstration of platelet aggregation mediated through direct P2X1 stimulation, supporting a role for this receptor in regulating platelet activation.