Days Of Receipt Research Articles

Removal Of Class Actions: What Danger Lurks InShady Grove

IN 2010, the Supreme Court of the United States delivered a landmark decision in Shady Grove Orthopedic Associates v. Allstate Insurance. (1) The case presented an extraordinarily complex combination of procedural issues, primarily concerning a crossroads between federal and state law in the context of class certification. The result was nothing short of bewildering. In a plurality opinion, a majority agreed that a New York statute prohibiting class actions in suits seeking penalties or statutory minimum damages was preempted by Rule 23 of the Federal Rules of Civil Procedure. (2) As a result, the petitioner's suit could proceed as a class action in federal court, while ironically it not have been able to do so in state court. In the opening opinion, Justice Scalia gave a broad, sweeping application of Rule 23, finding that it unambiguously authorizes any plaintiff, in any federal civil proceeding, to maintain a class action if the Rules' prerequisites are met. (3) But while Justice Stevens agreed with the result in this particular case, he disagreed with Justice Scalia's rationale, opining that if a federal procedural rule would displace a state law that is procedural in the ordinary use of the term but is so intertwined with a state right or remedy that it functions to define the scope of the state-created right, then the federal procedural rule cannot govern such a case. (4) Following Shady Grove, depending upon the proclivity of a district court to apply Justice Scalia's rigid, FRCP-deferential rationale, or Justice Stevens's more pragmatic theory, a motion for class certification could have strikingly different odds of success. If a district court follows Justice Scalia's approach, then the decision to remove a putative class action to federal court result in the loss of the very grounds--a state law prohibiting class certification--that otherwise defeat class certification in state court. However, should a district court follow Justice Stevens's approach, that same state law might apply even after removal, depending on whether it is so intertwined with the ability to proceed as a class action that it functions to define the scope of this right. Thus, before removing a putative class action, defense attorneys must be wary of the hidden dangers that lurk in the wake of Shady Grove. Part I of this Article will discuss the Shady Grove decision in further detail, outlining the factual and procedural background, the majority's judgment, and the divergence between Justice Scalia and Justice Stevens on the issue of whether Rule 23 preempts every state law regarding class actions. Part II will examine the practical effect that judges employing Justice Scalia's rationale will have on the future of class actions, and will analyze recent court decisions affected by this reasoning. Part III will explore the practical effect that courts using Justice Stevens's approach will have in forthcoming class action cases, and outline a series of cases that were determined under this method. This Article should provide defense practitioners with a sense of awareness when faced with the decision of whether to remove a class action to federal court, including the possibility that, ironically, this could result in certification of a class that otherwise might have been defeated in state court. I. The Shady Grove Decision A. Background The underlying dispute arose when a medical facility, Shady Grove Orthopedic Associates, attempted to revive a $5 million class action suit it had filed in federal court against Allstate Insurance Co. (5) In the suit, Shady Grove contended that Allstate regularly failed to provide timely payments of claims under a New York law that required insurance companies to pay legitimate claims within thirty days of receipt. (6) Alleging that Allstate routinely refused to pay interest on overdue benefits, and invoking the Class Action Fairness Act, Shady Grove sought relief on behalf of itself and a class of all others to whom Allstate owed interest. …

Factors associated with delays in head and neck cancer treatment: case-control study.

Delays in head and neck cancer treatment lead to increased mortality, more extensive treatment and patient anxiety. We aim to treat all patients with cancer within 62 days of receipt of a referral. An analysis was conducted of those patients whose treatment had been delayed in order to identify factors associated with treatment delay. In this retrospective case-control study, 50 patients whose treatment was delayed were identified and compared with 50 patients whose treatment was not delayed. Individual factors assessed included patient age, co-morbidity, tumour location and stage, the treatment agreed, the hospitals to which the patients were referred, and the clinicians they saw. There was a significant association between referral to a non-head and neck cancer centre, or review by a non-head and neck multidisciplinary team member, and treatment delay. In the context of centralisation of head and neck cancer services, it is important to consider delays that may be associated with a 'hub and spoke' model of service provision.

General practice encounters following seasonal influenza vaccination as a proxy measure of early-onset adverse events

BackgroundIn 2010, use of seasonal trivalent influenza vaccine (TIV) in children <5 years of age was suspended in Australia following reports of vaccine-related febrile convulsions. We investigated the utility of data on primary care [general practice (GP)] consultations for any reason within three days of receipt of influenza vaccine as recorded on the Australian Childhood Immunisation Register (ACIR) as a means of signal detection. MethodsData on GP consultations were obtained from Medicare Australia (Australian Government Department of Human Services) for children recorded on the ACIR as receiving either TIV or monovalent influenza vaccine. Rates of GP consultation by day following ACIR-recorded receipt of influenza vaccine were compared by year (2008–2010), vaccine type, age and region. ResultsIn 2010, GP encounter rates on the day after receipt of the TIV manufactured by bioCSL (formerly CSL Biotherapies (Fluvax®) were significantly higher than both bioCSL TIVs in the previous two years [rate ratio (RR) 1.9; 95% CI: 1.7–2.2] and Sanofi Pasteur TIV, Vaxigrip® [RR 1.6, 95% CI 1.4–1.7] in 2009–2010. Encounter rates were also higher than for CSL Monovalent influenza vaccine, Panvax® [RR 1.9, 95% CI 1.7–2.2] in 2009–2010. These findings were robust to adjustment for age group (≤2, >2 years) and region (Western Australia vs other Australian states/territories). ConclusionsA primary care consultation on the day after vaccine receipt is a reasonable proxy for early reactogenicity and has potential for use in various settings.

Announcement: HDL biology: new insights in metabolism, function and translation: to be published in July, 2014

Cardiovascular Research publishes Spotlight review issues devoted to a specific research topic. These issues contain a number of expert reviews, which can be complemented with original research papers on this topic. All papers are subjected to the normal peer review process (an editorial decision is usually made within 22 days of receipt of any manuscript). A Spotlight issue on ‘HDL biology: new insights in …

The Journal of Physiology Annual Report 2013–14:Another year of progress

We have just completed another busy and fruitful year for The Journal of Physiology as we continue our mission to promote excellence in the communication of physiology to the world. The Journal is without international boundaries, and below is a summary of where we have recently been, and where we plan to go in 2014–15. We value the support of our readers and those who publish their outstanding findings with us. At the beginning of 2013, The Journal of Physiology Consulting Editor Carol Robinson FRS was made a Dame Commander of the Most Excellent Order of the British Empire (DBE) for Services to Science and Industry. She is widely recognised for her ground-breaking research in mass spectrometry and as a role model for women scientists. In the 2014 New Year Honours list, Peter Ratcliffe FRS, another of The Journal's esteemed Consulting Editors, was awarded a knighthood for his services to clinical medicine. Sir Peter is Head of the Nuffield Department of Clinical Medicine based at the Henry Wellcome Building for Molecular Physiology in Oxford. His laboratory works on understanding the mechanisms by which cells sense and signal hypoxia. In 2013 we published a paper based on the Annual Review Prize Lecture which Peter delivered at Physiology 2012 (the annual meeting of The Physiological Society), Edinburgh, UK, 4 July 2012. Oxygen sensing and hypoxia signalling pathways in animals: the implications of physiology for cancer Ratcliffe PJ (2013) J Physiol 591, 2027–2042 http://jp.physoc.org/content/591/8/2027.full Sadly in 2013 we said goodbye to one of the legends in the field of physiology who had his Nobel Prize winning work in The Journal. David H. Hubel FRS passed away in October after a long and distinguished career in visual neuroscience. Physiology lost one of its giants. The Journal of Physiology lost one of its heroes. David H. Hubel – A man of vision J Physiol 592, issue 1. http://jp.physoc.org/content/592/1.toc

Trisomy 13 (Sy Patau)

Trisomy 13 (Sy Patau) is a clinically severe entity. 85% of the patients do not survive beyond one year, and most children die before completing six months of age. We report a female child, 30 day old, white, the third child of a non-consanguineous couple, who pre­sented trisomy 13. The child was born at term, from a vaginal delivery, weighing 3200 g. The second day of life the development of respiratory distress translated in KBC Kragujevac (release list no.29623). The initial clinical examination detected shisis primariy and secunday palate, ASD, stenosis rami AP, polidactily pedis dextri, microcornea and microftalmia. After 27 days of hospitalization in KBC Kragujevac, transferred to the Institute for mother and child New Belgrade, where he died after three days of receipt. During hospitalization blood samples were taken for determination of kariotip. Parents are advised that in case of subsequent pregnancies occur in the genet­ic counseling of the Institute for prenatal diagnosis.

Abstract PD4-3: Use of community-based next-generation sequencing (NGS) in advanced breast cancer: Identification of actionable targets to guide clinical trial selection

Abstract Background: Molecularly targeted drugs specific for mutated genes are increasingly the focus of novel clinical trials. However, molecular profiling of tumors is largely unavailable in community cancer centers, where nearly 80% of cancer patients (pts) are treated. In October 2012, Sarah Cannon Research Institute (SCRI) launched a community-based molecular profiling initiative to characterize the spectrum of molecular alterations in tumors. The profiling panel focused on potentially actionable mutations for the purpose of identifying candidates for treatment with specific targeted agents (FDA approved or investigational). Herein, we report the initial data from breast cancers (BC) profiled between October 2012 and May 2013. Methods: Metastatic breast cancer (MBC) pts &amp;gt; 18 years of age with ECOG PS ≤ 2 who were candidates for treatment provided consent for tumor molecular profiling. Archival tumor specimens (tissue block or 10 unstained slides) obtained from either the primary or metastatic disease were collected and interrogated by NGS (1000X average coverage) in a CLIA/CAP laboratory to detect oncogenic hotspot mutations in 35 cancer-related genes. Results were reported to the treating physician within 12 calendar days of receipt of suitable tissue and were stored in a database to enable correlation with clinical outcomes. Detection of relevant molecular abnormalities was used to identify pts appropriate for clinical trials of targeted agents. Results: As of May 31 2013, a total of 594 tumor samples were profiled, 101 (17%) of which were BC samples. 8% (8/101) of the BC samples were inadequate for assay. Of the remaining 93 samples, 60 (65%) had no mutations detected. 28% of BC had single mutations and 7% had multiple mutations. PIK3CA mutations (24%) were the most frequently identified alteration. Other genetic alterations identified included RUNX1 (4%) and FGFR3 (2%) while mutations in PIK3R1, MET, KRAS, KIT, FGFR2, HER2, BRAF, SMO, MYC, DDR2 and AKT1 were infrequent, each identified in 1 pt. Patterns and frequency of mutations in the 35 genes assayed differed in the various subtypes of BC. 6% (6/93) of BC pts with appropriate tumor mutations identified by molecular profiling have been enrolled into phase I clinical trials with PI3K or mTORC1/2 inhibitors; updated treatment results will be presented. An additional 27 patients are potentially eligible for ongoing trials at SCRI. Conclusions: This community-based molecular profiling initiative has been well accepted by patients and physicians, and provides timely results. Potentially actionable mutations were identified in 35% of BCs tested; PIK3CA mutations accounted for 70% of all actionable mutations detected. Identification of BC patients with actionable mutations may add to treatment options and improve results, and will also accelerate development of new targeted agents. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD4-3.

Editorial

Editorial

Performance of the new HIV-1/2 Diagnostic Algorithm in Florida's public health testing population: A review of the first five months of utilization

ObjectiveThe Centers for Disease Control and Prevention and the Association of Public Health Laboratories have proposed a new HIV-1/2 Diagnostic Algorithm: a fourth-generation HIV-1/2 Ag/Ab immunoassay (IA) followed, when repeatedly reactive, by an HIV-1/HIV-2 antibody differentiation test, and if that is non-reactive, HIV-1 nucleic acid amplification testing (NAT). The objective of the study was to evaluate performance of the new algorithm after five months of utilization in our high volume, high HIV-1 seroprevalence public health population. MethodsAlgorithm sensitivity and specificity was evaluated on 51,953 prospective serum or plasma specimens from individuals self-referring for HIV serostatus determination. Specimens were tested on the day of receipt or maintained at 4°C until the next testing opportunity. If the initial HIV-1/2 Ag/Ab IA (Abbott Combo) was nonreactive, a negative lab interpretation report would follow. If the initial IA was reactive, repeat screening in duplicate was immediately performed. Repeatedly reactive specimens were tested with an HIV-1/HIV-2 differentiation assay (Multispot [MS] HIV-1/HIV-2 Rapid Test) on the same or next workday. If the Abbott Combo-MS assays were discordant, HIV-1 NAT (APTIMA® HIV-1 RNA) was performed. In addition to the algorithm performance, we also evaluated the laboratory “specimen receipt to reporting” turnaround time (TAT). ResultsThe sensitivity and specificity of the new HIV Diagnostic Algorithm with serum and plasma specimens over the initial 5 month period was 100% (922/922) and 99.99% (51,030/51,031), respectively. Two algorithm-defined acute HIV-1 infections (AHI) were detected. In addition only 3 of the 992 MS secondary tests performed were interpreted as HIV-1 Indeterminate (HIV-1 recombinant gp41 reactivity only). Of these, 2 were HIV-1 NAT reactive, defined in-house as an early HIV infection (EHI) and one was HIV-1 NAT nonreactive, indicating a false positive initial screening result. Laboratory TAT for reporting concordant reactive Abbott Combo-MS results in ≤2 workdays was 96%, compared to 22% for reporting concordant reactive 3rd generation IA-Western blot results. ConclusionsIn our public health testing population, results from the new HIV Diagnostic Algorithm exceeded those of the 3rd generation IA-WB algorithm with respect to HIV-1 sensitivity. The identification of two algorithm-defined AHIs provided the opportunity to inform these individuals of their HIV status and link them to medical care earlier than the scheduled posttest counseling appointment.

Announcement: Heterocellular signalling and crosstalk in the heart in ischaemia and heart failure: to be published in May, 2014

Cardiovascular Research publishes Focus review issues devoted to a specific research topic. These issues contain a number of expert reviews, and part of each issue is reserved for original research papers. All papers are subjected to the normal peer review process (an editorial decision is usually made within 22 days of receipt of any manuscript). A Focus issue on …

Comparison of Established and Emerging Biodosimetry Assays

Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools.

PWE-021 An Investigation into High Gfobt Positivity During the First Five Days following sample Collection

IntroductionThe NHS Bowel Cancer Screening Programme (BCSP) in England has used the guaiac-based faecal occult blood test (gFOBt) since 2006. Test positivity is higher during the first 5 days after...

Mo1191 An Investigation of High gFOBT Positivity During the First Five Days Following Sample Collection

Introduction The NHS Bowel Cancer Screening Programme (BCSP) in England has used the guaiac-based faecal occult blood test (gFOBt) since 2006. Test positivity is higher during the first 5 days after sample collection. Methods The gFOBt kits used by the BCSP have six windows (three pairs) lined with guaiac-impregnated philtre paper. The screening participant is asked to apply two faecal samples from three separate stools. The samples usually arrive dry at the laboratory, which is likely to reduce the degree of haemoglobin (Hb) degradation and provide the best opportunity to detect bleeding. BCSP policy is that every kit is logged on the day of receipt and read as soon as possible thereafter. BCSP Southern Hub data from the Bowel Cancer Screening System (BCSS) for 01/2008–07/2012 were analysed for subjects aged 60–69 years completing the first prevalent round of screening. The interval between each sample date and the date the sample was analysed (elapsed time) was calculated. Spot positivity was assessed by elapsed time, stratified by sex. Clinical outcomes were extracted from BCSS for subjects who had a positive gFOBt result. The relationship between positivity, elapsed time and clinical outcomes was examined. Results During the period of observation, nearly 1.2 million kits were returned to the Hub and 92% were read within five days of the last sample collection. For samples analysed one day after the last sample collection, spot positivity was 2.7% for women and 3.8% for men. Positivity declined thereafter until it reached a steady level at day 5 (women 1.3%; men 2.0%). Positivity for the most recently collected sample (usually spots 5 and 6) was slightly higher than for the spots collected earlier. There were 20,408 subjects (8,343 women; 12,065 men) who accepted further investigation. The outcome of those investigations was not associated with elapsed time between faecal sampling and test kit reading; the proportion of cancers, high-, intermediate- and low-risk adenomas was fairly constant as elapsed time increased. Conclusion The higher positivity associated with a shorter elapsed time did not appear to be associated with more false-positive tests. A number of factors may contribute to the pattern of positivity observed: (a) vegetable peroxidases present in the diet cause short term increases in gFOBt positivity; (b) faecal Hb denatures gradually before analysis, and (c) screening invitees worried about their health may return test kits more rapidly than others and a proportion of those individuals will be found to have colorectal cancer and related disease. None of those factors alone can account for the marked elevation in the ‘early positivity rate’ and further studies are required to elucidate the reasons for this effect. Disclosure of Interest None Declared.

Mo1192 Impact of Incidental Findings of 18 FDG-PET/CT in the Patients With Gastric Cancer

Background The NHS Bowel Cancer Screening Programme (BCSP) in England has used the guaiac-based faecal occult blood test (gFOBt) since 2006. The kits have six windows (three pairs) lined with guaiac-impregnated filter paper to which two faecal samples from three consecutive stools are applied. The samples usually arrive dry at the laboratory, which is likely to reduce the degree of haemoglobin (Hb) degradation and provide the best opportunity to detect bleeding. The amount of bleeding from bowel cancer lesions and adenomas is directly related to the degree of bowel pathology. BCSP policy is that every kit is logged on the day of receipt and read as soon as possible thereafter. Test positivity is higher during the first 5 days after sample collection, but the reasons for this are unclear. Vegetable peroxidases in the diet and their rapid degradation in faeces is one possible explanation. Method BCSP Southern Hub data from the Bowel Cancer Screening System for 01/200807/2012 were analysed for subjects aged 60-69 years completing the first prevalent round of screening. The interval between each sample date and the date the sample was analysed (elapsed time) was calculated. Spot positivity was assessed by elapsed time, stratified by sex. Clinical outcomes were extracted from BCSS for subjects who had a positive gFOBt result. The relationship between positivity, elapsed time and clinical outcomes was examined. Results Overall, 92% of test kits were read in the Hub within 5 days of the last sample collection. For samples analysed one day after the last sample collection, spot positivity was 2.7% for women and 3.8% for men. Positivity declined thereafter until it reached a steady level at day 5 (women 1.3%; men 2.0%). Positivity for the most recently collected sample (spots 5 and 6) was slightly higher than for the spots collected earlier. There were 20,408 subjects (8,343 women; 12,065 men) referred for further investigation after gFOBt testing during the study period. The outcome of those further investigations was not associated with elapsed time between faecal sampling and test kit reading; the proportion of cancers, high-, intermediate and low-risk adenomas was fairly constant as elapsed time increased. Conclusions The higher positivity associated with a shorter elapsed time is not associated with a higher proportion of false-positive tests. There is the possibility that the fairly constant yield of false and true positives over time could reflect a balance between vegetable peroxidase degradation and the degradation of Hb associated with various degrees of pathology. Conversely, the higher positivity during the first few days after sample collection might be explained simply by the possibility that worried (perhaps symptomatic) individuals may return the test kit for analysis more quickly. Further work is required to confirm these observations.

Abstract 3523: Quantitative measurements of EGFR pathway signaling and modulation in pleural effusion samples from non-small cell lung cancer (NSCLC) patients using single cell network profiling (SCNP).

Abstract Background: SCNP is a multiparametric flow cytometry-based assay that quantitatively and simultaneously measures, at the single cell level, both extracellular surface markers and activation levels of intracellular signaling proteins in response to modulation. SCNP has been successfully applied to hematologic malignancies in both prognostic and predictive analyses. Previous work using bladder washes from bladder cancer patients (pts) established the feasibility of applying SCNP to the functional characterization of epithelial cell signaling and response to modulation and targeted kinase inhibition in non-conventional samples. Objectives: Assess the feasibility of applying SCNP to detect and functionally characterize epithelial cells, including sensitivity to targeted kinase inhibition, in pleural effusion (PE) samples from NSCLC pts. Methods: PE from confirmed NSCLC pts (n=4) were collected at the NSUH and shipped overnight to Nodality for processing on day of receipt. Antibodies to CD45, CytoKeratin (CK), EpCAM, and cPARP were used to differentiate non-apoptotic epithelial cells from leukocytes. DNA aneuploidy was evaluated using the lymphoid population in the patient samples as a diploid G0/G1 reference. Signaling in PI3K and MAPK pathways was quantified through measurement of p-AKT and p-ERK levels at baseline and after in vitro exposure to EGF +/- PI3K inhibitor GDC-0941. The epithelial bladder carcinoma cell line HT-1376 was used as a positive control for epithelial phenotypic staining and EGF-induced signaling. Results: In 3 of 4 PE samples, epithelial cells (DAPI+, CD45-, CK+, and EpCAM+) were identified (range 0.35% to 15.87% of all nucleated cells). Epithelial cells had a DNA index &amp;gt;1.3, indicating aneuploidy and therefore tumor origin. The majority of epithelial cells were cPARP negative (&amp;gt;80%) and suitable for SCNP analysis. In all 3 samples with epithelial cells: 1) EGF modulation induced increased p-AKT and p-ERK; 2) Pre-treatment with GDC-0941 inhibited EGF induced p-AKT but not p-ERK; 3) Constitutive activation of the PI3K pathway in the tumor epithelial cells was suggested by reduction in p-AKT levels compared to basal (no EGF exposure) following GDC-0941 treatment. Conclusion: This study demonstrates the feasibility of applying SCNP to the functional characterization of PE samples from NSCLC pts. Ongoing analyses will expand upon these data, including both additional NSCLC PE samples and the evaluation of compounds targeting alternative signaling pathways relevant to NSCLC (eg: MAPK, EGFR). The feasibility of extending such SCNP analyses to other solid tumor indications, using alternative tissue sources and circulating tumor cells, is under further investigation for both prognostic and response predictive utility. [S.Z. Fields and H. Raftopoulos are senior co-authors.] Citation Format: Matt Westfall, Rachael Hawtin, Todd Covey, Michael Gulrajani, Michelle Atallah, Michelle Cholankeril, Reena Vora, Alessandra Cesano, Scott Z. Fields, Haralambos Raftopoulos. Quantitative measurements of EGFR pathway signaling and modulation in pleural effusion samples from non-small cell lung cancer (NSCLC) patients using single cell network profiling (SCNP). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3523. doi:10.1158/1538-7445.AM2013-3523

Red Blood Cell-Encapsulated L-Asparaginase: Potential Therapy of Patients with Asparagine Synthetase Deficient Acute Myeloid Leukemia

Red blood cell (RBC) encapsulated L-asparaginase is a novel therapeutic for the treatment of asparagine auxotrophic malignancies. The enzyme-loaded red blood cells function as bioreactors to deplete bloodstream substrate. This delivery system provides improved pharmacodynamics with protection from circulating proteolytic enzymes and avoidance of early liver or renal clearance. The “drug” is manufactured with ABO and Rh compatible donor blood when a prescription is received. Because of the industrial scale manufacturing, the “drug” is transfused the day of receipt at the clinical site. Preliminary clinical studies show utility in childhood and adult acute lymphoblastic leukemia. Based on previous studies of applications in different diseases and assessment of different biomarkers, we propose this agent offers a safe and potentially effective treatment for a subset of chemotherapy refractory acute myeloid leukemia patients. The history, chemistry, biology, pharmacology, and relevant clinical experiences with L-asparaginase as well as the properties and proposed protocols with the red cell-encapsulated enzyme are reviewed.

Red Blood Cell-Encapsulated L-Asparaginase: Potential Therapy of Patients with Asparagine Synthetase Deficient Acute Myeloid Leukemia

Red blood cell (RBC) encapsulated L-asparaginase is a novel therapeutic for the treatment of asparagine auxotrophic malignancies. The enzyme-loaded red blood cells function as bioreactors to deplete bloodstream substrate. This delivery system provides improved pharmacodynamics with protection from circulating proteolytic enzymes and avoidance of early liver or renal clearance. The "drug" is manufactured with ABO and Rh compatible donor blood when a prescription is received. Because of the industrial scale manufacturing, the "drug" is transfused the day of receipt at the clinical site. Preliminary clinical studies show utility in childhood and adult acute lymphoblastic leukemia. Based on previous studies of applications in different diseases and assessment of different biomarkers, we propose this agent offers a safe and potentially effective treatment for a subset of chemotherapy refractory acute myeloid leukemia patients. The history, chemistry, biology, pharmacology, and relevant clinical experiences with L-asparaginase as well as the properties and proposed protocols with the red cell-encapsulated enzyme are reviewed.

Failure to correct International Normalized Ratio and mortality among patients with warfarin‐related major bleeding: an analysis of electronic health records

Delayed correction of blood clotting times as measured by the International Normalized Ratio (INR) is associated with adverse outcomes among certain patients with warfarin-related major bleeding. However, there are limited data on the association between INR correction and mortality. To assess factors associated with 30-day mortality and time to death in patients receiving fresh frozen plasma (FFP) for warfarin-associated major bleeding. A retrospective database analysis was undertaken with electronic health record data from a large integrated health system. Patients met the following criteria: major hemorrhage diagnosis; INR ≥ 2 on the day before or day of receipt of FFP; and prescription fill for warfarin within 90 days. INR correction (defined as INR ≤ 1.3) was evaluated at the last available test 1 day following the start of FFP administration. Kaplan-Meier curves and Cox proportional hazards models were constructed to assess mortality. Four hundred and five patients met the selection criteria (mean age of 75 years, 54% male), and 67% remained uncorrected at 1 day following the start of FFP administration. Among all patients, 11% died within 30 days of hospital admission. An uncorrected INR was not associated with a higher risk of 30-day mortality for patients overall, but was statistically significant for the subgroup with intracranial hemorrhage (ICH) (adjusted odds ratio 2.55; 95% confidence interval 1.04-6.28). Among the subgroup of major bleeding patients with warfarin-associated ICH, those not correcting to either INR ≤ 1.3 or INR ≤ 1.5 with the use of FFP have an increased rate of mortality at 30 days.

Review panel forActa Crystallographica Section F

When Acta Crystallographica Section F was being established in 2004, one of the principal goals was for it to take advantage of its online and other attributes to provide rapid processing of articles and minimize the time from submission to publication. One of the early ideas for accelerating article processing was championed by former Section Editor Mitchell Guss: enrolling a panel of experienced referees specially committed to minimizing the time taken for peer review. This review panel was implemented in 2009 and now nears completion of two years of service. Each member of the expert panel has agreed to accept 12 referee requests a year, to accept or decline to review an article within two days of receipt of a request, and to return a report within two weeks. A panel of about 30 referees allows each Acta Cryst. F Co-editor to use a panel member as one of the referees for each paper they manage. The intended effect of the panel is to help reduce the referee response time, the time waiting for the return of a review, and the delays incurred when requests are declined late and new referees must be recruited. The initial panel of 30 was recruited late in 2009 and began in earnest in 2010, coincident with installation of our new electronic submission and review system. By all accounts, the panel members have exceeded expectations in fulfillment of their referee duties and did so with a flourish, adding extra value by providing incisive and helpful reviews. All were offered reappointment for 2011 and, with a couple of exceptions, all accepted. Two have also been promoted to the position of Co-editor. A list of the current panel members (together with our Co-editors) may be found at http://journals.iucr.org/f/services/editors.html. The following are some of the inaugural panel members: Raghuvir Arni, Miriam-Rose Ash, John Badger, Bichitra Biswal, David Borhani, Debasish Chattopadhyay, Peter Dunten, Jose Gavira, Brian Geisbrecht, F. Xavier Gomis-Ruth, Yoshiki Higuchi, Li-Wei Hung, Masami Kusunoki, Kon Ho Lee, Oded Livnah, Andrea Mattevi, Jochen Mueller-Dieckmann, Sanjeev Munshi, Craig Ogata, Sam-Yong Park, Jean-Denis Pedelacq, Bernhard Rupp, Seong Eon Ryu, Boaz Shaanan, Linda Shimon, Titia Sixma, Frank von Delft and Francis Tsai. All are also listed in the World Directory of Crystallography (http://scripts.iucr.org/cgi-bin/chub_search). We would like to thank all previous and current members of the panel for their dedicated service to our journal, to our authors and to our science.

P40 Fast track jaundice clinic: the standard of care for hepatobiliary malignancy?

IntroductionThe Scottish Government has stated that 95% of people referred urgently with a suspicion of cancer should begin treatment within 62 days of receipt of referral.1 Dedicated fast track clinics...