A seafood risk tool for assessing and mitigating chemical and pathogen hazards in the aquaculture supply chain.

Intricate links between aquatic animals and their environment expose them to chemical and pathogenic hazards, which can disrupt seafood supply. Here we outline a risk schema for assessing potential impacts of chemical and microbial hazards on discrete subsectors of aquaculture-and control measures that may protect supply. As national governments develop strategies to achieve volumetric expansion in seafood production from aquaculture to meet increasing demand, we propose an urgent need for simultaneous focus on controlling those hazards that limit its production, harvesting, processing, trade and safe consumption. Policies aligning national and international water quality control measures for minimizing interaction with, and impact of, hazards on seafood supply will be critical as consumers increasingly rely on the aquaculture sector to supply safe, nutritious and healthy diets.

Evaluation of the protection against norovirus afforded by E. coli monitoring of shellfish production areas under EU regulations.

EC Regulation 854/2004 requires the classification of bivalve mollusc harvesting areas according to the faecal pollution status of sites. It has been reported that determination of Escherichia coli in bivalve shellfish is a poor predictor of norovirus (NoV) contamination in individual samples. We explore the correlation of shellfish E. coli data with norovirus presence using data from studies across 88 UK sites (1,184 paired samples). We investigate whether current E. coli legislative standards could be refined to reduce NoV infection risk. A significant relationship between E. coli and NoV was found in the winter months (October to February) using data from sites with at least 10 data pairs (51 sites). We found that the ratio of arithmetic means (log10 E. coli to log10 NoV) at these sites ranged from 0.6 to 1.4. The lower ratios (towards 0.6) might typically indicate situations where the contribution from UV disinfected sewage discharges was more significant. Conversely, higher ratios (towards 1.4) might indicate a prevalence of animal sources of pollution; however, this relationship did not always hold true and so further work is required to fully elucidate the factors of relevance. Reducing the current class B maximum (allowed in 10% of samples) from 46,000 E. coli per 100 g (corresponding NoV value of 75750 ± 103) to 18,000 E. coli per 100 g (corresponding NoV value of 29365 ± 69) reduces maximum levels of NoV by a factor of 2.6 to 1; reducing the upper class B limit to 100% compliance with 4,600 E. coli per 100 g (corresponding NoV value of 7403 ± 39) reduces maximum levels of NoV by a factor of 10.2 to 1. We found using the UK filtered winter dataset that a maximum of 200 NoV corresponded to a maximum of 128 ± 7 E. coli per 100 g. A maximum of 1,000 NoV corresponded to a maximum of 631 ± 14 E. coli per 100 g.

Fluoroscopy-guided reduction and fibular nail fixation to manage unstable ankle fractures in patients with diabetes: a retrospective cohort study.

AIMS: Patients with diabetes are at increased risk of wound complications after open reduction and internal fixation of unstable ankle fractures. A fibular nail avoids large surgical incisions and allows anatomical reduction of the mortise. PATIENTS AND METHODS: We retrospectively reviewed the results of fluoroscopy-guided reduction and percutaneous fibular nail fixation for unstable Weber type B or C fractures in 24 adult patients with type 1 or type 2 diabetes. The re-operation rate for wound dehiscence or other indications such as amputation, mortality and functional outcomes was determined. RESULTS: Two patients developed lateral side wound infection, one of whom underwent wound debridement. Three other patients required re-operation for removal of symptomatic hardware. No patient required a below-knee amputation. Six patients died during the study period for unrelated reasons. At a median follow-up of 12 months (7 to 38) the mean Short Form-36 Mental Component Score and Physical Component Score were 53.2 (95% confidence intervals (CI) 48.1 to 58.4) and 39.3 (95% CI 32.1 to 46.4), respectively. The mean Visual Analogue Score for pain was 3.1 (95% 1.4 to 4.9). The mean Ankle Osteoarthritis Scale total score was 32.9 (95% CI 16.0 to 49.7). CONCLUSION: Fluoroscopy-guided reduction and fibular nail fixation of unstable ankle fractures in patients with diabetes was associated with a low incidence of wound and overall complications, while providing effective surgical fixation. Cite this article: Bone Joint J 2016;98-B:1197-1201.

Clinical and radiographic outcomes of the mobility total ankle arthroplasty system: early results from a prospective multicenter study.

BACKGROUND: The Mobility Total Ankle System is a third-generation design consisting of a 3-component, cementless, unconstrained, mobile-bearing prosthesis. This study reports the early results of a prospective multicenter study of the Mobility prosthesis. METHODS: Eighty-eight Mobility total ankle arthroplasties (TAAs) were implanted in 85 patients. The most common underlying diagnosis was posttraumatic arthritis (53%). Ankles were classified according to the Canadian Orthopedic Foot and Ankle Society (COFAS) end-stage ankle arthritis classification system. Coronal plane deformity was quantified preoperatively. Patients were reviewed at regular intervals postoperatively, with clinical and radiographic assessment. The mean follow-up time was 40 months (range, 30-60 months). RESULTS: Type 1 ankle arthritis was demonstrated in 44 ankles (50%). No patient had preoperative coronal plane angulation greater than 20 degrees. In 32 ankles (36%) the preoperative coronal alignment was neutral, and in 34 ankles (39%) the deformity was less than 10 degrees. The mean American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot score improved from 38.2 (range, 12-59) preoperatively to 74.8 (range, 46-100) postoperatively. Bone-implant interface abnormalities were identified in 33 ankles with a retained prostheses (43%). Thirty (91%) of these involved zones around the tibial plate. In total, 8 TAAs required revision, 6 for aseptic loosening, 1 for talar migration, and 1 for deep infection. There was 1 conversion to arthrodesis for component malpositioning and 1 transtibial amputation for chronic regional pain syndrome. Six patients were being investigated for ongoing pain. The cumulative survival was 89.6% (95% confidence interval, 80.8-94.8) at 3 years and 88.4% (95% confidence interval, 79.3-93.9) at 4 years. CONCLUSION: Early results of the Mobility TAA for independent researchers do not match those reported by other surgeons. Good pain relief and improved function were achieved postoperatively in 72 ankles (82%). High rates of bone-implant interface abnormalities around the tibial plate are concerning but require longer follow-up to determine their clinical significance.

Phase I pharmacokinetic and pharmacodynamic study of the pan-PI3K/mTORC vascular targeted pro-drug SF1126 in patients with advanced solid tumours and B-cell malignancies.

BACKGROUND: SF1126 is a peptidic pro-drug inhibitor of pan-PI3K/mTORC. A first-in-human study evaluated safety, dose limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of SF1126, in patients with advanced solid and B-cell malignancies. PATIENTS AND METHODS: SF1126 was administered IV days 1 and 4, weekly in 28day-cycles. Dose escalation utilised modified Fibonacci 3+3. Samples to monitor PK and PD were obtained. RESULTS: Forty four patients were treated at 9 dose levels (90-1110 mg/m(2)/day). Most toxicity was grade 1 and 2 with a single DLT at180 mg/m(2) (diarrhoea). Exposure measured by peak concentration (C(max)) and area under the time-concentration curve (AUC(0-)(t)) was dose proportional. Stable disease (SD) was the best response in 19 of 33 (58%) evaluable patients. MTD was not reached but the maximum administered dose (MAD) was 1110 mg/m(2). The protocol was amended to enrol patients with CD20+ B-cell malignancies at 1110 mg/m(2). A CLL patient who progressed on rituximab [R] achieved SD after 2 months on SF1126 alone but in combination with R achieved a 55% decrease in absolute lymphocyte count and a lymph node response. PD studies of CLL cells demonstrated SF1126 reduced p-AKT and increased apoptosis indicating inhibition of activated PI3K signalling. CONCLUSION: SF1126 is well tolerated with SD as the best response in patients with advanced malignancies.

HLA class II antigen presentation by prostate cancer cells.

Prostate cancer is the second most commonly diagnosed cancer in men. Recent evidence suggests that reduced expression of target protein antigens and human leukocyte antigen (HLA) molecules is the predominant immune escape mechanism of malignant prostate tumor cells. The purpose of this study was to investigate the prospect of antigen specific immunotherapy against prostate cancer via the HLA class II pathway of immune recognition. Here, we show for the first time that prostate cancer cells express HLA class II proteins that are recognized by CD4+ T cells. Prostate tumor cells transduced with class II molecules efficiently presented tumor-associated antigens/peptides to CD4+ T cells. This data suggests that malignant prostate tumors can be targeted via the HLA class II pathway, and that class II-positive tumors could be employed for direct antigen presentation, and CD4+ T-cell mediated tumor immunotherapy.Prostate Cancer and Prostatic Diseases (2008) 11, 334-341; doi:10.1038/sj.pcan.4501021; published online 16 October 2007.

Total knee arthroplasty in Paget's disease: technical problems and results.

Eleven total knee arthroplasties performed in 10 patients with Paget's disease were reviewed at 2 to 16 years postoperatively. Cemented total knee arthroplasties were performed in all cases. Range of motion improved by 21 degrees postoperatively and the follow-up Knee Society score averaged 83 points. One knee was rated poor with a score <70 points; this knee was the only knee with a loose component. All components resting on pagetic bone had a solid interface on radiographic review at an average of 5.7 years postoperatively. Although technical difficulties are encountered in achieving correct alignment and exposing the knee with local Paget's disease, good long-term outcome can be achieved.

Fixed-weight on-line learning.

Conventional artificial neural networks perform functional mappings from their input space to their output space. The synaptic weights encode information about the mapping in a manner analogous to long-term memory in biological systems. This paper presents a method of designing neural networks where recurrent signal loops store this knowledge in a manner analogous to short-term memory. The synaptic weights of these networks encode a learning algorithm. This gives these networks the ability to dynamically learn any functional mapping from a (possibly very large) set, without changing any synaptic weights. These networks are adaptive dynamic systems. Learning is online continually taking place as part of the network's overall behavior instead of a separate, externally driven process. We present four higher order fixed-weight learning networks. Two of these networks have standard backpropagation embedded in their synaptic weights. The other two utilize a more efficient gradient-descent-based learning rule. This new learning scheme was discovered by examining variations in fixed-weight topology. We present empirical tests showing that all these networks were able to successfully learn functions from both discrete (Boolean) and continuous function sets. Largely, the networks were robust with respect to perturbations in the synaptic weights. The exception was the recurrent connections used to store information. These required a tight tolerance of 0.5%. We found that the cost of these networks scaled approximately in proportion to the total number of synapses. We consider evolving fixed weight networks tailored to a specific problem class by analyzing the meta-learning cost surface of the networks presented.

Surgical exposures in revision total knee arthroplasty.

A well-planned operative approach to revision total knee arthroplasty is crucial to a successful outcome. Wide exposure must be achieved to allow component removal, soft-tissue balancing, management of bone loss, and reimplantation without damaging important structures. These structures include skin, the extensor mechanism, the collateral ligaments, the remaining bone stock, and neurovascular structures. Skin necrosis can be avoided by selecting the appropriate incision and dissecting deep to the fascia. Extensile exposure by dissection of scar, quadriceps snip or turndown, tibial tubercle osteotomy, or medial epicondylar osteotomy should be performed early to prevent patellar tendon disruption. In certain cases, the distal femur can be exposed circumferentially by using a quadriceps myocutaneous flap or femoral peel. Special care should be taken with the infected or ankylosed knee.

Periprosthetic hip and knee fractures: the scope of the problem.

This review covers the present incidence, site, and outcome of periprosthetic fractures of the hip and the knee. Fractures can occur intraoperatively or postoperatively as an early or a late complication. Late postoperative fractures are related to osteolysis secondary to wear debris. These late fractures will become more prevalent with time. Intraoperative fractures can be avoided by careful technique and improved instrument design. Fractures can affect the acetabulum, femur, and trochanter of hip replacements: and the femur, tibia, and patella of knee replacements. The femur is most commonly involved for both joints. Stress fractures have been described as a rare complication of both sites of arthroplasty. If the fracture is recognized and the bone stock is good, a good outcome can be achieved if rigid fixation is obtained Unfortunately poor bone stock is often present, leading to late periprosthetic fractures, which compromise the outcome.

The role of diagnostic block in the management of Morton's neuroma.

OBJECTIVE: To determine the outcome of surgical excision of Morton's neuroma after a local anesthetic diagnostic block into the neuroma has relieved symptoms. DESIGN: A cohort study. SETTING: A university affiliated hospital. PATIENTS: A sequential series of 37 patients who underwent 41 excisions with at least 2 years' follow-up. Seven patients had undergone repeat excision of a neuroma, and 34 primary excisions were performed. Surgery was performed by a specialist in orthopedic surgery of the foot and ankle. INTERVENTION: Excision of the Morton's neuroma after a positive diagnostic block. MAIN OUTCOME MEASURES: Grade of symptoms at follow-up done by independent review on a 4-point scale. RESULTS: Of 41 procedures, 11 had an unfavourable outcome: 4 procedures were graded 3, and 7 procedures were graded 4. Eight (24%) of the 34 primary procedures were reported as failures, and 3 (43%) of the 7 revision procedures were reported as failures. Most patients reported poor results owing to persistent pain. CONCLUSIONS: Diagnostic blocks do not improve the results of surgery for excision of Morton's neuroma and are not recommended. Because failure rates are greater than 20%, surgery for Morton's neuroma should only be offered after a full course of nonoperative management.

Treatment of infection associated with segmental bone loss in the proximal part of the femur in two stages with use of an antibiotic-loaded interval prosthesis.

Treatment of an infection at the site of a total hip replacement associated with extensive loss of the proximal part of the femur is a challenging problem. In the present preliminary report, we describe the results after use of a prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) in thirty such hips. The purpose of the prosthesis, which acts as an internal splint, is to maintain the length of the femur as well as the range of motion of the joint and the mobility of the patient between stages. A local level of antibiotics is maintained by the antibiotic-coated surface. A PROSTALAC with a cement-on-cement articulation was used in the first fifteen hips (Group I) in the study, and a custom metal-on-polyethylene articulating PROSTALAC was inserted in the subsequent fifteen hips (Group II). One patient who had a recurrent infection was managed with a second two-stage exchange and was included in both groups. Between stages, the average limb-length discrepancy was twenty-five millimeters despite a loss of more than 25 per cent of the femur in nineteen limbs. Sixteen patients were discharged home and seven, to a community hospital between stages. Six patients in Group I and only one in Group II were hospitalized for the entire course of treatment. The total duration of hospitalization for both stages averaged thirty-eight days. Twenty-eight patients were mobile even though they did not bear weight on the involved limb between stages: three patients used a cane, fifteen used crutches, and ten used a walker. Twenty-six patients reported no, slight, or moderate pain in the thigh, groin, or buttock between stages. The average Harris hip score before the first stage of the operation was 23 points (range, 0 to 63 points), which improved to 74 points (range, 40 to 91 points) at an average of forty-seven months (range, twenty-four to 114 months) postoperatively. Two patients died of unrelated causes before two years (the minimum follow-up period) had elapsed and were excluded from the final analysis; they had no evidence of recurrent infection. Of the remaining twenty-eight hips, twenty-seven (96 per cent) had no evidence of infection at the most recent follow-up examination.

The outcome of two-stage arthroplasty using a custom-made interval spacer to treat the infected hip.

Sixty-one patients undergoing a two-stage revision of an infected hip using a prosthesis of antibiotic-loaded acrylic cement were followed for an average of 43 months. Twelve patients were excluded (3 died, 6 had no proven infection, and 2 no second stage). Only 1 patient was lost to follow-up evaluation from those included, for a retrieval rate of 98% for those still living. Of the remaining 48 patients, 3 had further sepsis: Two became reinfected with different organisms and 1 with the same organism, for an infection eradication rate of 94%. The other 45 had no clinical, laboratory, or radiographic evidence of infection. Thirty-seven patients (80%) had a Harris hip score greater than 80 or an improvement of at least 30 points.

Factors affecting fracture position at cast removal after pediatric forearm fracture.

The outcome of a pediatric forearm fracture is related to the angulation of that fracture at the time of union. We discuss the factors affecting the position of the fracture at union. Three hundred forty-six children with 369 reductions of forearm fractures were reviewed retrospectively. Quality of reduction at the time of operation and loss of reduction during the period of cast immobilization were assessed using axis deviation. Loss of reduction had a greater influence on the final position of the fracture at union than did the position of the fracture at initial reduction. To ensure a satisfactory outcome, all pediatric forearm fractures should be monitored with radiologic review and remanipulation if their axis deviation is > 5 in younger patients or > 3 in patients with fractures close to or after growth-plate closure. Right forearm fractures in boys were identified as a subgroup at greater risk for redisplacement.

Position of the knee joint after total joint arthroplasty.

A method for assessing knee joint position after surgery using the preoperative long-leg radiograph and the postoperative knee radiograph is described. Assessment of the formula has shown a near perfect correlation between the calculated position on the long-leg radiograph compared with the measured position for 44 knees. Three hundred eighteen knees after total joint arthroplasty were retrospectively reviewed and the postoperative position was determined. The preoperative position of the mechanical axis was 14.5 +/- 37.3 mm medial to the knee joint center. Using the standing knee radiograph the postoperative position of the mechanical axis was 3.07 +/- 9.2 mm lateral to the knee joint center, while the portable radiograph placed the mechanical axis 4.5 +/- 12.4 mm medial to the knee joint center. There was a highly significant difference in the position of the knee joint center depending on the radiograph used for calculation (standing or portable). The difference between the two means was not due to opening of the knee joint, but likely due to change in the rotation of the knee in the presence of knee flexion. This series of the knee arthroplasties has a low projected rate of aseptic failure.

Femoral forces during limb lengthening in children.

A system was designed to measure forces during femoral lengthening using force transducers on an Ilizarov femoral frame. Measurements were made in three teenaged subjects overnight and during weight bearing. A progressive increase in axial load secondary to distraction was seen, forces peaking at 428, 447, and 673 N for the three subjects. Little change in force transmitted by the frame was observed during weight bearing. Measurements taken before and after each individual lengthening showed no change in axial force or bending moment (p > 0.01). A diurnal variation of axial load was found (p < 0.01). Forces at midnight were greater than in the morning in all the subjects, with a mean difference of 113 N (p < 0.01). Distraction forces measured in the femur during distraction are greater than those previously measured in the tibia. Evidence exists that the callus is stiff and may be the origin of these forces.

Accurate prediction of outcome after pediatric forearm fracture.

Factors affecting outcome after pediatric forearm fracture include fracture angulation and fracture position. A new index, axis deviation, combines these factors. Two review studies were performed to determine if axis deviation correlated with outcome. In the first study, 35 subjects were reviewed 2.7 years after fracture without radiographs. In the second study, 152 fractures were reviewed a mean of 4 years after fracture, with 124 patients consenting to undergo radiographs. In both studies, the new index, axis deviation, correlated better with restricted forearm movement than either degree of angulation or fracture position. Midshaft and distal remodeling occurred and could be predicted in terms of axis deviation. We propose that an axis deviation of < 5 at the time of union be the reduction criteria of pediatric forearm-shaft fracture regardless of fracture position.

Aggression and social withdrawal as viewed by children's peers: conceptual issues in assessment and implications for intervention.

Children's peer assessments of aggressive and withdrawn behavior are fundamentally related to developmental changes in their understanding of others. This article synthesizes research relevant to the thesis that peer assessments are dependent on children's ability both to recall the previous behavior of their peers and to predict their likely future behavior. Social schema theory, borrowed from adult social psychology, is highly relevant to such recall and prediction. Age differences, affective biases, and gender roles may color children's assessments of their peers' social behavior. Such influences should be taken into account when conceptualizing interventions aimed at enhancing children's peer status, and in measuring the success of these interventions.