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Purpose: Associations between taxane-related sensory neuropathy (TRSN) and single-nucleotide polymorphisms (SNP) have previously been reported, but few have been replicated in large, independent validation studies. This study evaluates the association between previously investigated SNPs and TRSN, using genotype data from a study of chemotherapy-related toxicity in patients with breast cancer.Experimental Design: We investigated 73 SNPs in 50 genes for their contribution to TRSN risk, using genotype data from 1,303 European patients. TRSN was assessed using National Cancer Institute common toxicity criteria for adverse events classification. Unconditional logistic regression evaluated the association between each SNP and TRSN risk (primary analysis). Cox regression analysis assessed the association between each SNP and cumulative taxane dose causing the first reported moderate/severe TRSN (secondary analysis). The admixture likelihood (AML) test, which considers all SNPs with a prior probability of association with TRSN together, tested the hypothesis that certain SNPs are truly associated.Results: The AML test provided strong evidence for the association of some SNPs with TRSN (P = 0.023). The two most significantly associated SNPs were rs3213619(ABCB1) [OR = 0.47; 95% confidence interval (CI), 0.28–0.79; P = 0.004] and rs9501929(TUBB2A) (OR = 1.80; 95% CI, 1.20–2.72; P = 0.005). A further 9 SNPs were significant at P-value ≤ 0.05.Conclusion: This is currently the largest study investigating SNPs associated with TRSN. We found strong evidence that SNPs within genes in taxane pharmacokinetic and pharmacodynamic pathways contribute to TRSN risk. However, a large proportion of the inter-individual variability in TRSN remains unexplained. Further validated results from GWAS will help to identify new pathways, genes, and SNPs involved in TRSN susceptibility. Clin Cancer Res; 20(9); 2466–75. ©2014 AACR.

PDF file - 237KB, Supplementary Table 1: Published Studies of Putative Functional SNPs Supplementary Table 2a: Drug Regimens and Doses of Taxanes by Study Supplementary Table 2b: Comparison of Toxicity grades/rates by recruiting trial in PGSNPS included in Taxane Related Sensory Neuropathy Study Supplementary Table 3: PGSNPS Taxane Treated Patient Characteristics Supplementary Table 4: All Putative Functional SNPs Replicated in the PGSNPS dataset (phenotype: cumulative dose to TRSN) Supplementary Table 5: All Putative Functional SNPs Replicated in the PGSNPS dataset (phenotype: maximum TRSN) Supplementary Figure 1: Percentage of Patients with TRSN ≥ grade 2 by genotype, for three statistically significant SNPs that were genotyped in PGSNPS (maximum TRSN) Supplementary Figures 2a-c: Kaplan-Meier curves Kaplan-Meier curves: Shows for each SNP, by genotype, the probability of TRSN grade 0-1 (i.e., the probability of not experiencing moderate/severe TRSN) as the cumulative dose increases.

Purpose To determine whether platelet-rich plasma (PRP) injection for lateral epicondylitis offers patients comparable outcomes to lateral epicondylar surgery. Methods Embase, Cochrane Library, and MEDLINE databases were searched using the terms lateral epicondylitis, lateral elbow pain, tennis elbow, lateral epicondylalgia, and elbow tendinopathy individually and combined with the terms platelet-rich plasma injections and lateral epicondylar surgery. We compared pain relief, function between the 2 treatment options, and identified whether PRP injection reduced the incidence of lateral epicondylar surgery. Studies must have compared PRP injections with lateral epicondylar surgery for the treatment of lateral epicondylitis; be of Level I, II, or III evidence; and be written in the English language. Results Three studies (1 Level II and 2 Level III) met inclusion criteria. Two of the studies suggested that PRP injections offer similar relief as surgery in the short and mid-term, one study reported that PRP injections and surgery had similar outcomes in pain improvement and return to work, whereas 1 study reported that surgery may be a better long-term solution. Conclusions In comparison with lateral epicondylar surgery, PRP injections offer similar improvements in pain and function for patients suffering from lateral epicondylitis, especially in the short- and mid-term in 2 of the 3 included investigations. Therefore, PRP injections are an appropriate alternative for the treatment of lateral epicondylitis. Level of Evidence Level III, Systematic Review of Level III or greater evidence.

The use of ionising radiation (IR) for medical diagnosis and treatment procedures has had a major impact on the survival of paediatric patients. Although the benefits of these techniques lead to efficient health care, evaluation of potential associated long-term health effects is required. HARMONIC aims to better understand the increased risk of cancer and non-cancer effects after exposure to medical IR in children with cancer treated with modern external beam radiotherapy (EBRT) – radiation energy in MeV range – and in children with cardiac defects diagnosed and treated with cardiac fluoroscopy procedures (CFP) – radiation energy in keV range. The project investigates, among survivors of paediatric cancer, potential endocrine dysfunction, cardiovascular and neurovascular damage, health-related quality of life and second (and subsequent) primary cancer (SPC). The cardiac component builds a pooled cohort of approximately 90 000 paediatric patients who underwent CFP during childhood and adolescence to investigate cancer risk following exposure to IR and explore the potential effects of conditions predisposing to cancer. HARMONIC develops software tools to allow dose reconstruction in both EBRT and CFP to enable epidemiological investigations and future optimisation of treatments. With the creation of a biobank of blood and saliva samples, HARMONIC aims to provide a mechanistic understanding of radiation-induced adverse health effects and identify potential biomarkers that can predict these effects.

We sought to determine which demographic characteristics influence energy drink consumption habits and to examine whether caffeine content and knowledge of human nutrition affect college students' decisions to consume these beverages. We used an online survey to ask 265 college students, who did not participate in a varsity sport, to complete a survey consisting of demographic questions, the General Knowledge Questionnaire for adults, and questions about energy drink consumption habits. We found, overall, that 23.1% of our sample used energy drinks. When compared to non-consumers (76.9%), users had a significantly lower GPA, were older, and preferred drinks with a higher caffeine content. Users reported that they consumed these drinks because they wanted to feel more alert and they enjoyed the taste, even though they reported adverse effects such as trouble sleeping, shaking and tremors, and stomachaches. Knowledge of human nutrition did not affect users' choice to consume these drinks. Although the majority of college students do not consume energy drinks, room for improvement remains to curb the use of these caffeinated beverages amongst college students.

To instill quality in published clinical research, reporting guidelines, consisting of checklists and flowcharts, were developed to protect against reporting poorly designed research, and researchers should be aware of the available instruments and their appropriate use. With the popularity of synthetic reviews, meta-analyses, and systematic reviews, there is a greater need to assess risk of bias and study quality. This review highlights the most frequently used guidelines and checklists, risk-of-bias scales, and quality rating scales that can assist researchers with improving their research and its eventual publication.

The Himalayas are of exceptional importance for the water resources in Asia and provide fresh water for more than 1.4 billion people. However, they are also the source of frequent floods with the highest death-per-event rates in the world. The floods are caused by intense monsoon precipitation, but snow melt and glacier melt contribute to the flood peaks. Both, extreme precipitation and melt contributions are predicted to be impacted by climate change but it remains unclear how these changes will alter the flood risk in the region.This study investigates the impact of climate change on peak runoffs in the transboundary Karnali River Basin (KRB) in Nepal / China using both hydrological and statistical modelling. The fully-distributed cryospheric-hydrological model SPHY is applied for the period 2002-2015 and calibrated and validated using the GLUE framework. The Nash-Sutcliffe efficiency, PBIAS of peak flows and extended GLUE are used as performance indicators for the selection of behavioural parameter sets. The model is run with the selected parameter sets and the outputs of 13 downscaled and bias-corrected CMIP-6 models of three different scenarios (historical, ssp245, ssp585) to quantify the climate-change-induced changes in peak flows until the end of the century. Extreme Value Analysis is then applied to estimate the exceedance probability from the simulated annual maximum flows for the climate models, scenarios and hydrological parameter sets.The results indicate an increase in flood hazard frequency and magnitude until the end of the century. The mean magnitude of an event with 2% annual exceedance probability (AEP) increases by 23% (±19%) in the period 2020 - 2059, and 42% (±19%) in the period 2060 - 2099 for ssp245, and 28% (±23%) in the period 2020 - 2059 and 82% (±41%) in the period 2060 - 2099 for ssp585 compared to the baseline period (1975 - 2014). Flows with a 50 year return period (2% AEP) during the baseline period (10,900 m3/s) are projected to occur every 9 years in the period 2020 - 2059 and 7 years in the period 2060 - 2099 for ssp245 scenario, and every 9 and 3 years for ssp585 scenario, respectively. Glacier and snowmelt contributions are projected to change in terms of seasonality and quantity but the increase of peak flows is mainly driven by the increase in extreme precipitation.

PURPOSE OF REVIEW: Rates of obesity and reverse total shoulder arthroplasty (rTSA) in the USA have both escalated with time. Obese patients experience arthritis at higher rates than normal weight patients; therefore, these numbers go hand in hand. Obesity has been correlated with health comorbidities such as anxiety, cardiovascular disease, diabetes, and metabolic syndrome as well as poorer outcomes and higher complication rates following lower extremity arthroplasty. The current review investigates these comorbidities as they relate to obese patients undergoing rTSA. RECENT FINDINGS: Functional outcomes are similar to normal weight counterparts. Although longer operative times and a large soft tissue envelope would intuitively predispose these patients to higher risk for infection or other complications, this has not been reliably demonstrated. Technical considerations and awareness of potential risks in the obese patient demographic may aid the surgeon in preoperative planning and counseling of their patient. SUMMARY: Obese patients undergoing rTSA have been shown to have higher risks specifically for infection, revision, and medical complications; however, this has not been consistently demonstrated in the single surgeon series where, more often, no difference in these metrics has been found. Outcomes measures and satisfaction are reliably improved, even when considering superobese patients, and majority of studies find their improvements and absolute values to be in line with their normal weight counterparts. Thus, rTSA does not seem to carry the same level of adverse risk associated with lower joint arthroplasty but potential for higher risk still bears consideration when counseling obese patients. Attention to factors that may negatively affect prosthesis positioning may optimize retention rates and limit early failure.

Background: Patient reported outcome measures assess clinical progress from the patient’s perspective. This study explored the relationship between shoulder outcome measures (The Disability of the Arm, Shoulder and Hand [DASH], American Shoulder and Elbow Surgeons Standard Shoulder Assessment score [ASES], and Constant score) by comparing the best possible scores obtained in an asymptomatic population compared to overall perception of health, as measured by the SF-36 outcome measure.Methods: Volunteers (age range, 20?69 years) with asymptomatic shoulders and no history of shoulder pain, injury, surgery, imaging, or pathology (bilaterally) were included. The DASH and ASES measures were completed by 111 volunteers (72 female, 39 male), of which 92 completed the Constant score (56 female, 36 male). The SF-36 was completed by all volunteers (level of evidence: IV case series).Results: The mean (x) score for ASES measure on the right shoulder was higher for the left-hand dominant side (x=100.00 vs. 95.02, p-value

Concussions are a brain injury that affects the athlete on and off the playing field. The aim of our investigation was to give PE teachers another strategy to use in addition to the recommended approaches set forth by national organizations to convey the message to adolescents regarding the negative effects of concussion. Using the website www.mlssoccer.com, we evaluated the performance measures of MLS players. We compared career performance measures of a control group to the career performance measures of a concussed group, compared career performance measures per position, and compared career performance measures occurring prior to concussion onset to performance measures obtained after concussion occurrence for the concussed group. Of the 2,214 listed players, 288 were eligible for the study. From our sample, 34% sustained a concussion while competing in MLS and 66% were placed in the control group (nonconcussed). In a comparison of the control to the concussed group, total number of shots decreased per season for the concussed group. When the performance measures of both groups were compared by position, midfielders had fewer shots per season, and total shots on goal per season had a trend toward statistical significance. In the comparison of games measures before and after concussion, the total number of seasons and the average games played, total minutes, and shots on goal all decreased per season after concussion occurrence. Concussions negatively affected performance measures of MLS players. PE teachers can use this data to engage with their students about the importance of preventing concussions.

Lateral patellar dislocations can damage the medial patella femoral ligament. Nonoperative care is preferred but some tears may require a surgical intervention. Patella fractures are considered a risk factor after surgery. The technique described in this Technical Note avoids any bone tunnel drilling, which may eliminate the possibility of a patella fracture. The surgical procedure uses periosteal fibro-osseous tunnels to a double-limbed gracilis graft to reconstruct the upper and lower borders as conventionally used for medial patella femoral ligament reconstruction. Once the graft is tensioned, it is sutured to the periosteal fibro-osseous tunnel with 2 sutures on the medial side and at least 1 suture on the lateral side of each periosteal fibro-osseous sleeve. Each of the 2 periosteal fibro-osseous tunnels has 3 to 4 sutures securing the graft. After surgery, the patients complete 5 phases of rehabilitation to reduce swelling and to regain their strength and range of motion.

MOTIVATION: Proper management of fecal sludge has significant positive health and environmental externalities. Most research on managing onsite sanitation so far either simulates the costs of, or the welfare effects from, managing sludge in situ in pit latrines. Thus, designing management strategies for onsite rural sanitation is challenging, because the actual costs of transporting sludge for treatment, and sources for financing these transport costs, are not well understood. METHODS: In this paper we calculate the actual cost of sludge management from onsite latrines, and identify the contributions that latrine owners are willing to make to finance the costs. A spreadsheet-based model is used to identify a cost-effective transport option, and to calculate the cost per household. Then a double-bound contingent valuation method is used to elicit from pit-latrine owners their willingness-to-pay to have sludge transported away. This methodology is employed for the case of a rural subdistrict in Bangladesh called Bhaluka, a unit of administration at which sludge management services are being piloted by the Government of Bangladesh. RESULTS: The typical sludge accumulation rate in Bhaluka is calculated at 0.11 liters/person/day and a typical latrine will need to be emptied approximately once every 3 to 4 years. The costs of emptying and transport are high; approximately USD 13 per emptying event (circa 14% of average monthly income); household contributions could cover around 47% of this cost. However, if costs were spread over time, the service would cost USD 4 per year per household, or USD 0.31 per month per household-comparable to current expenditures of rural households on telecommunications. CONCLUSION: This is one of few research papers that brings the costs of waste management together with financing of that cost, to provide evidence for an implementable solution. This framework can be used to identify cost effective sludge management options and private contributions towards that cost in other (context-specific) administrative areas where onsite sanitation is widespread.

Context: Higher serum TSH levels, both within the reference range and in those with subclinical hypothyroidism (SCH), have been associated with increased risk of atherosclerosis and cardiovascular (CV) events in a number of cross-sectional and longitudinal studies. Objective: Our objective was to evaluate blood thrombogenicity in patients post–non-ST elevation acute coronary syndrome (NSTE-ACS) in relation to their thyroid function. Design, Patients, and Outcome Measure: At 1 week after troponin-positive NSTE-ACS, 70 patients who had been treated with optimal antiplatelet and secondary prevention therapy were studied. Patients with known thyroid disease or on medications affecting thyroid function were excluded. Blood thrombogenicity was assessed using the ex vivo Badimon perfusion chamber. Results: Serum TSH was associated with higher thrombus burden (β = .30; P = .01) independent of other well-established CV risk factors. Patients with SCH (n = 12; 17%) had a higher thrombus burden than euthyroid individuals as evidenced by the area of the thrombus: mean (SD) 23 608 (10 498) vs 16 661 (10 902) μm2/mm (P = .02). However, this association was not evident when the analysis was limited to patients with serum TSH within the reference range. In addition, neither serum free T4 nor free T3 had any significant association with thrombus area. Conclusion: Serum TSH levels, particularly in the SCH range, are associated with higher thrombus burden despite optimal recommended secondary prevention therapy after NSTE-ACS. This may explain the higher CV risk seen in SCH patients. Future trials to assess the effect of individualized antithrombotic as well as thyroid hormone replacement therapy to reduce atherothrombotic risk in this population are needed.

Background Cytotoxic chemotherapy is widely used for advanced, unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours (NETs) and the most commonly used regimen combines 5-fluorouracil with streptozocin. The NET01 trial was designed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin. Methods Patients with advanced, unresectable NETs of pancreatic, gastrointestinal foregut or unknown primary site were randomised to receive three-weekly capecitabine (Cap) 625mg/m 2 twice daily orally, streptozocin (Strep) 1.0g/m 2 intravenously on day 1, with or without cisplatin (Cis) 70mg/m 2 intravenously on day 1. The primary outcome measure was objective response. Secondary outcome measures included progression-free and overall survival, quality of life, toxicity and biochemical response. Results 86 (44 CapStrep, 42 CapStrepCis) patients were randomised. Best objective response rate was 12% (95% confidence interval (CI)=2–22%) with CapStrep and 16% (95% CI=4–27.4%) with CapStrepCis. Disease-control rate was 80% with CapStrep and 74% with CapStrepCis. The estimated median progression-free and overall survival were 10.2 and 26.7months for CapStrep and 9.7 and 27.5months for CapStrepCis. 44% of CapStrep and 68% of CapStrepCis patients experienced grade ⩾3 adverse events. Interpretation The efficacies of the novel CapStrep±Cis regimens were very similar. CapStrep was better tolerated than CapStrepCis. The trial was registered as EudraCT: 2004-005202-71 and ISRCTN: 35124268.

BACKGROUND: Correctly distinguishing gliomas as low or high grade (LGG or HGG) during surgery can influence the surgical procedure, enhancing resection and improving survival. The UK NCRI GALA-BIDD study was designed to prospectively investigate whether the presence of visible fluorescence is a pragmatic intra-operative diagnostic surgical biomarker of high-grade disease within a tumour mass in real time during surgery. METHODS: Patients with suspected intrinsic glioma discussed at neuro-oncology Multidisciplinary Team meetings and suitable for fluorescence guided cytoreductive surgery were eligible. 5-aminolevulinic acid (5-ALA) was used to generate visible fluorescence. Samples of fluorescent tissue were sent for peri-operative histopathological analysis to establish an intra-operative diagnosis of LGG or HGG. These data were compared with the final central pathological diagnosis. RESULTS: From Feb 2015 to March 2017 in the UK, 106 patients were recruited: median age 59 (range 23–77); 59% male; 25% WHO radiological grade II transforming to a higher grade and 55% grade IV. 5-ALA were given for 103 patients with a median dose of 1500mg (range 960-2200mg). 67% of patients classified as HGG at local peri-operative diagnosis were confirmed by the central review (weighted Kappa 0.37 (95%CI=0.21–0.54)). 88 patients were evaluable for the primary endpoint: 81 had visible fluorescence of the tumour with central histopathology diagnosis as 1 LGG, 78 HGG (a 99% concordance in HGG classification with the 99%CI=91%-99.9%) and 2 not assessed; 7 patients had no visible fluorescence and were diagnosed as 6 LGG and 1 HGG. CONCLUSION: There is an urgent need to improve the local peri-operative diagnosis. The presence of visible fluorescence can be used as an additional pragmatic intra-operative diagnostic surgical biomarker of high-grade disease within a tumour mass. Use for assessment of low-grade disease needs further investigation.

Objectives: Baseball pitchers are among the most valued players in major league baseball because of their influence on the outcome of a game. Anecdotal cases suggest that pitching more innings, arbitrarily determined to be 160 innings a year, may shorten careers. Our hypothesis was that pitchers who threw more innings/year before age 25 would have a shorter career. Methods: Inclusion criteria were baseball pitchers who entered the Major League System from 1989-1992 only including those with no missing information for the following variables: Average Innings pitched per year before and after age 25, Earned Run Average (ERA), Walks and Hits divided by Innings Pitched (WHIP), Strike to Walk ratio (SWR), Strikeouts, Walks, Length of career, starting and Retirement age. 96 pitchers met those criteria. We did not analyze career statistics since these are created after the respective player's career ends rather analyzed their statistics before age 25. The information was obtained from http://www.baseball-reference.com . We used ANOVA to compare differences between groups and a regression model to assess relationship between variables (statistics) before age 25 and career length. Results: The mean number of innings pitched per year before age 25 was 66.6, Confidence Interval (CI) 12.90-120.3. In fact, only 11 of 96 pitchers threw over 148 innings/year. ERA (mean 5.51 CI: 2.50-8.52) and WHIP (mean 1.66, CI: 1.04-2.28) may be most commonly used measurements of pitcher performance. If pitchers are divided by those who throw 80 innings/year or over, 28 over and 68 under, the over 80 innings/year before age 25 group had significantly better ERA's (4.20, CI: 2.52-5.88 vs 6.03, CI: 2.66-9.40, P=.0087), WHIP's (1.35 CI: .98-1.72 vs 1.79 CI: 1.13-2.45, P=.0012), and longer careers (13.1, CI: 8.5-17.7 years vs 8.7, CI: 2.8-14.6 years, P=.0007). In fact, the regression analysis between career length and innings pitched per year before age 25 is a positive relationship with an R2 of .15, suggesting 15% of the career length variability is positively associated with the number of innings pitched per year before age 25. ERA and WHIP had weak positive relationship with career length, R2=.039 and R2=.025 respectively. Conclusion: Pitchers who threw over 80 innings a year before age 25, had the lowest ERA's, WHIP's, and the longest careers. Our hypothesis was disproved. In this population, there was not an advantage to restricting the number of innings pitched before age 25 for a young pitcher.

Background: Pyridoxine is frequently used to treat capecitabine-induced hand–foot syndrome (HFS), although the evidence of benefit is lacking. We performed a randomised placebo-controlled trial to determine whether pyridoxine could avoid the need for capecitabine dose modifications and improve outcomes. Methods: A total of 106 patients planned for palliative single-agent capecitabine (53 in each arm, 65%/ 35% colorectal/breast cancer) were randomised to receive either concomitant pyridoxine (50 mg po) or matching placebo three times daily. Results: Compared with placebo, pyridoxine use was associated with an increased rate of avoiding capecitabine dose modifications (37% vs 23%, relative risk 0.59, 95% CI 0.29, 1.20, P=0.15) and fewer grade 3/4 HFS-related adverse events (9% vs 17%, odds ratio 0.51, 95% CI 0.15–1.6, P=0.26). Use of pyridoxine did not improve response rate or progression-free survival. Conclusion: Pyridoxine may reduce the need for capecitabine dose modifications and the incidence of severe HFS, but does not impact on antitumour effect.

Biographie et hommage a Michael R. Bonavia, expert de l'economie du transport en Grande-Bretagne et historien du transport ferroviaire britannique. Il collabora egalement a de nombreux ouvrages portants sur les grands travaux du 20e siecle, tels que le tunnel sous la Manche...

To identify the relationships between energy drink consumption, nutrition knowledge, and socio-demographic characteristics in a convenience sample of student-athletes.Cross-sectional.Online survey.A total of 194 student-athletes (112 female and 82 male).Socio-demographic characteristics, knowledge of human nutrition, energy drink consumption habits.Chi-square tests of independence, independent t tests, and hierarchical regression analyses were applied.Most student-athletes in the sample (85.5%) did not consume energy drinks, but those who did tended to be male (P = .004), had lower overall knowledge of nutrition (P = .02), and had a lower grade point average (P .001) than did nonusers. Also, energy drink consumption was associated with the overall nutrition knowledge score when adjusted for socio-demographic characteristics, with nonusers having greater nutrition knowledge (P = .007) than users.Student-athletes tend to refrain from energy drink use but those who use it have a tendency to have lower nutrition knowledge than do nonusers. Therefore, nutrition education targeted toward student-athletes should encompass the consumption of energy drinks because limited evidence shows the benefits of collegiate athletes consuming energy drinks.

Background: PDAC carries a poor prognosis. Recently ABX combined with GEM was shown to improve overall survival compared with standard single agent GEM. The mechanism by which ABX and GEM interact is not fully understood, but limited preclinical and clinical data has led to two hypotheses: 1: ABX may act to deplete the tumour stroma by binding to the protein, SPARC (secreted protein acidic and rich in cysteine), facilitating GEM penetration of and access to the tumour; 2: ABX may increase intratumoural levels of the active GEM triphosphate by decreasing cytidine deaminase (CDA) activity, thus enhancing GEM cytotoxicity. Mouse models of PDAC suggest that delivery of ABX 24 hours prior to GEM might result in even higher intratumoural GEM concentrations. Thus, scheduling of these 2 agents may be critical to optimising clinical benefit. Optimal scheduling of ABX + GEM and effect on quality of life is the subject of the SIEGE clinical trial. Trial design: Patients with previously untreated, histologically or cytologically confirmed metastatic PDAC are randomised to receive a 4-weekly cycle of ABX + GEM until disease progression, administered either concomitantly (IV ABX 125mg/m2 d1, d8 and d15 immediately followed by IV GEM 1000mg/m2 d1, d8 and d15) or sequentially (the same regimen with GEM given 24hr after ABX). Prior to randomisation, tumour tissue and blood is obtained for analysis of the tumour stroma, SPARC and CDA activity. Blood is collected prior to each treatment cycle and on disease progression. Tumour biopsies are collected prior to starting cycle 3 and at disease progression. The clinical primary endpoint is progression-free survival. Tumour assessments are performed using RECIST every 8 weeks until progression. Recruitment started in January 2014 and a total of 120 patients will be recruited over 2 years at 20 UK sites. Biological samples will be used to determine the mechanism of action of ABX + GEM. Biomarker analyses may identify whether a particular patient subgroup is likely to benefit more than others. The trial is registered as EudraCT 2013-001868-40. Disclosure: P. Corrie: I have received funds from Celgene Ltd for: 1. Work in a consultant/advisory role 2. As research funding 3. To fund travel to conferences/meetings; D.I. Jodrell and B. Basu: I have been awarded funds by Celgene Ltd for: 1. To fund aspects of my research. 2. To fund travel to conferences/meetings; J.W. Valle: I have received funds from Celgene Ltd for: 1. Work in a consultant/advisory role 2. As research funding 3. To fund travel to conferences/meetings. All other authors have declared no conflicts of interest.

Administration of a monoclonal antibody (GK1.5) that recognizes the L3T4 marker present on helper T cells prevented the development of experimental allergic encephalomyelitis (EAE) in mice. Furthermore, treatment with GK1.5 reversed EAE when the antibody was given to paralyzed animals. In vivo injection of GK1.5 selectively reduced the number of L3T4+ cells in the spleen and the lymph nodes. These results suggest that manipulation of the human equivalent of the murine L3T4+ T-cell subset with monoclonal antibodies may provide effective therapy for certain autoimmune diseases.

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