Uncertainty in environmental health impact assessment: Quantitative methods and perspectives

Environmental health impact assessment models are subjected to great uncertainty due to the complex associations between environmental exposures and health. Quantifying the impact of uncertainty is important if the models are used to support health policy decisions. We conducted a systematic review to identify and appraise current methods used to quantify the uncertainty in environmental health impact assessment. In the 19 studies meeting the inclusion criteria, several methods were identified. These were grouped into random sampling methods, second-order probability methods, Bayesian methods, fuzzy sets, and deterministic sensitivity analysis methods. All 19 studies addressed the uncertainty in the parameter values but only 5 of the studies also addressed theuncertainty in the structure of the models. None of the articles reviewed considered conceptual sources of uncertainty associated with the framing assumptions or the conceptualisation of the model. Future research should attempt to broaden the way uncertainty is taken into account in environmental health impact assessments.     

Murine and human zona pellucida 3 derived from mouse eggs express identical O-glycans

Murine sperm initiate fertilization by binding to the outer covering of the egg known as the murine zona pellucida (mZP). This binding is thought to require the interaction of O-glycans linked to a specific mZP glycoprotein (mZP3) with egg-binding proteins coating the sperm plasma membrane. The precise molecular basis of this interaction remains to be resolved. In this study, we analyzed the O-glycosylation of the individual mZP glycoproteins by using ultrasensitive MS methods. We found that the majority of the O-glycans that are linked to mZP3 are core type 2 sequences terminated with sialic acid, lacNAc (Galbeta1-4GlcNAc), lacdiNAc (Gal-NAcbeta1-4GlcNAc), Galalpha1-3Gal, and NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4 (Sda antigen). Many of these terminal sequences have been implicated previously in murine sperm-egg binding. Core type 1 O-glycans are also present and are generally unmodified, although some are terminated with sialic acid, beta-linked N-acetylhexosamine, or NeuAcalpha2-3[GalNAcbeta1-4]Galbeta1-4. Eggs expressing human ZP (huZP) glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. Sequencing of huZP3-associated O-glycans confirms that this implication is correct. The data obtained in this investigation may prove to be very useful for studies to determine the precise molecular basis of initial murine sperm-egg binding.     

Platelet enriched plasma for acute muscle injury

Hamstring muscle strains are among the most common injuries in sport, but despite increasing research into the epidemiology, aetiology and management the rates of both injury and re-injury remain high. Typically, hamstring injury management is conservative, but recently the use of autologous platelet enriched plasma (PEP), has been proposed as a treatment tool which may optimise muscle regeneration and enhance clinical outcomes. Unfortunately however, there remains little scientific evidence for the clinical use of these techniques in muscle injuries. This report outlines the current clinical evidence for the use of PEP in muscle injuries. A case report of a patient with a grade II semi-membranosus muscle strain, injected with PEP while concurrently using platelet inhibitors will illustrate the clinical, radiological and theoretical challenges of this new technique. Further clinical research into the clinical utility of PEP in muscle injury is required and it is incumbent on Sports Physicians and researchers to address this research deficit, if PEP is to live up to its high public profile.     

Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment

OBJECTIVE: Anti-CD20-mediated B cell depletion with rituximab is a new and effective therapy for rheumatoid arthritis (RA). Although B cells in peripheral blood (PB) are consistently depleted in all patients, the clinical effects are more heterogeneous, possibly related to differences in the depleting effects of lymphoid or solid tissues. The aim of this study was to investigate B cell depletion in different compartments (PB, bone marrow, and synovium) and determine predictive variables for responsiveness to rituximab therapy. METHODS: Before and 12 weeks after rituximab treatment, samples of PB, bone marrow, and synovium were collected from 25 patients with RA refractory to disease-modifying antirheumatic drugs and tumor necrosis factor-blocking agents. CD19+ and CD20+ B cells in PB and bone marrow were measured by flow cytometric analysis, whereas CD79a+ and cytoplasmic CD20+ B cells in the synovium were stained by immunohistochemistry. The effects of rituximab on serum Ig and autoantibodies were measured by enzyme-linked immunosorbent assay. RESULTS: Rituximab effectively depleted the CD20+ subset of B cells in the PB, bone marrow, and synovium of RA patients. Rituximab significantly reduced autoantibody production (anti-citrullinated protein antibodies [ACPAs] and rheumatoid factor [RF]), in part due to a nonspecific decrease in total Ig production. Importantly, positivity for circulating ACPA IgM, in combination with a high infiltration of CD79a+ B cells in the synovium, but not of CD138+ plasma cells, was a predictor of clinical outcome after rituximab treatment. ACPA IgM titers were independently associated with synovial infiltration of CD20-,CD79a+ B cells, but not with CD138+ plasma cells. CONCLUSION: These data provide novel insights into the mechanisms of CD20-mediated B cell depletion in the lymphoid and solid tissues of RA patients and suggest a pivotal role for ACPA IgM-producing plasmablasts in RA.     

Submandibular gland stones, a clinical review

The purpose of this study is to highlight the role of per-oral extraction of submandibular calculi in the management of salivary sialadenitis. This study was based on a retrospective review of patients presenting with submandibular sialadenitis over a 5-year period. 26 patients presented with a history of sialadenitis, with a palpable stone in the floor of the mouth and were considered candidates for surgery. 21 (80%) underwent per-oral extraction using marsupialization of the duct to maintain duct patency. 4 (15%) were deemed unsuitable when assessed under general anaesthesia due to inaccessible calculi. 2 (9%) of the 21 patients that underwent per-oral extraction required gland excision, due to persistence of symptoms. The remaining 19 (91%) are symptom free with a mean follow-up of 18 months. There were no neurological post-operative sequelae in the group. 1 patient had no surgical intervention at the end. In conclusion, per-oral extraction of submandibular salivary calculi is a safe method of relieving symptoms due to sialadenitis in patients with palpable accessible calculi in the floor of the mouth.     

Control analysis of the Rose-Hindmarsh model for neural activity

It is well known that vasopressin cells fire action potentialsin bursts, but also have the ability to continuously dischargeor have long periods of silence. Experimentally, various externalstimuli can be applied to the vasopressin cell in order tomanipulate the patterns of discharge observed. In this paper, the Rose–Hindmarsh model is used to describe the dischargingof a single vasopressin cell. The range of parameter valueswhich makes the model display the various patterns observedin vivo are described. It is shown that the model can be controlledto follow desired patterns of discharge and thus mimic externalstimulation.     

Synthesis, in vitro binding profile, and central nervous system penetrability of the highly potent 5-HT3 receptor antagonist [3H]-4-(2-methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole

4-(2-Methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole (5) is a highly potent member of a structurally novel series of selective serotonin-3 receptor antagonists. The synthesis of tritiated 5 and its binding profile in neuroblastoma-glioma 108-15 cells are described. Furthermore, in vivo studies in rat with this radioligand indicate that it effectively penetrates the blood-brain barrier upon peripheral administration. Thus, 5 should be a useful pharmacological tool for both in vitro and in vivo studies of this class of compounds.     

Optimisation of the T-square sampling method to estimate population sizes

Population size and density estimates are needed to plan resource requirements and plan health related interventions. Sampling frames are not always available necessitating surveys using non-standard household sampling methods. These surveys are time-consuming, difficult to validate, and their implementation could be optimised. Here, we discuss an example of an optimisation procedure for rapid population estimation using T-Square sampling which has been used recently to estimate population sizes in emergencies. A two-stage process was proposed to optimise the T-Square method wherein the first stage optimises the sample size and the second stage optimises the pathway connecting the sampling points. The proposed procedure yields an optimal solution if the distribution of households is described by a spatially homogeneous Poisson process and can be sub-optimal otherwise. This research provides the first step in exploring how optimisation techniques could be applied to survey designs thereby providing more timely and accurate information for planning interventions.     

Programme personnalisé de l’après cancer (PPAC)

The second Cancer Plan launched in November 2009 by the INCa emphasizes the desire to not only strengthen the support for cancer patients during the active phase of treatment but also develop a Personalized care Program for After Cancer treatment (PPAC). This program, designed to fit into the continuity of the Personalized Care Program (PCP), is elaborated jointly by cancer specialists and general practitioners before being explained and given to patients at the end of the active therapy period. The approach, innovative and new for many health care stakeholders, aims at several goals: to ensure the best possible care for patients in terms of monitoring and evaluation of risk of relapse as well as in preventing the risk of second cancer and taking into consideration social aspects. In this context, the implementation of the PPAC needs to follow several steps: build the content, define a format and design thatmeet the requirements defined by the INCa and fulfill the expectations of all health care stakeholders including, in particular, general practitioners, who are at the heart of this program. However, beyond content and format, the modalities of PPAC implementation represent the most critical step. Success will depend upon physicians??involvement and commitment in carrying the processes, the proper definition of responsibilities, the fulfillment of health care stakeholders??expectations, the short- and long-term quality of follow-up, the proper management of changes induced by the PPAC as well as its monitoring and assessment. Success requires that we get commitment, listen, convince, respect but not impose.