5 research outputs found
Current research priorities in chronic fatigue syndrome/myalgic encephalomyelitis: Disease mechanisms, a diagnostic test and specific treatments
No full textChronic fatigue syndrome (CFS) is an illness characterised by disabling fatigue of at least 6 months duration, which is accompanied by various rheumatological, infectious and neuropsychiatric symptoms. A collaborative study group has been formed to deal with the current areas for development in CFS research—namely, to develop an understanding of the molecular pathogenesis of CFS, to develop a diagnostic test and to develop specific and curative treatments. Various groups have studied the gene expression in peripheral blood of patients with CFS, and from those studies that have been confirmed using polymerase chain reaction (PCR), clearly, the most predominant functional theme is that of immunity and defence. However, we do not yet know the precise gene signature and metabolic pathways involved. Currently, this is being dealt with using a microarray representing 47 000 human genes and variants, massive parallel signature sequencing and real-time PCR. It will be important to ensure that once a gene signature has been identified, it is specific to CFS and does not occur in other diseases and infections. A diagnostic test is being developed using surface-enhanced, laser-desorption and ionisation-time-of-flight mass spectrometry based on a pilot study in which putative biomarkers were identified. Finally, clinical trials are being planned; novel treatments that we believe are important to trial in patients with CFS are interferon-ß and one of the anti-tumour necrosis factor- drugs
Fundamental Limits of Throughput and Availability: Applications to prophet inequalities & transaction fee mechanism design
No full textThis paper studies the fundamental limits of availability and throughput for independent and heterogeneous demands of a limited resource. Availability is the probability that the demands are below the capacity of the resource. Throughput is the expected fraction of the resource that is utilized by the demands. We offer a concentration inequality generator that gives lower bounds on feasible availability and throughput pairs with a given capacity and independent but not necessarily identical distributions of up-to-unit demands. We show that availability and throughput cannot both be poor. These bounds are analogous to tail inequalities on sums of independent random variables, but hold throughout the support of the demand distribution. This analysis gives analytically tractable bounds supporting the unit-demand characterization of Chawla, Devanur, and Lykouris (2023) and generalizes to up-to-unit demands. Our bounds also provide an approach towards improved multi-unit prophet inequalities (Hajiaghayi, Kleinberg, and Sandholm, 2007). They have applications to transaction fee mechanism design (for blockchains) where high availability limits the probability of profitable user-miner coalitions (Chung and Shi, 2023).34 pages, 7 figures; updated author information to include institutions and email addresses 35 pages, 7 figures; updated the TFM section and the last paragraph in the Applications sectio
How I treat transfusional iron overload
No full textPatients with β-thalassemia major (TM) and other refractory anemias requiring regular blood transfusions accumulate iron that damages the liver, endocrine system, and most importantly the heart. The prognosis in TM has improved remarkably over the past 10 years. This improvement has resulted from the development of magnetic resonance imaging (MRI) techniques, especially T2*, to accurately measure cardiac and liver iron, and from the availability of 3 iron-chelating drugs. In this article we describe the use of MRI to determine which adult and pediatric patients need to begin iron chelation therapy and to monitor their progress.We summarize the properties of each of the 3 drugs, deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX), including their efficacy, patient acceptability, and side effects. We describe when to initiate or intensify therapy, switch to another drug, or use combined therapy. We also discuss the management of refractory anemias other than TM that may require multiple blood transfusions, including sickle cell anemia and myelodysplasia. 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Oxidative Stress and Mitochondrial Injury in Chronic Multisymptom Conditions: From Gulf War Illness to Autism Spectrum Disorder
No full textBackground: Overlapping chronic multisymptom illnesses (CMI) include Chronic Fatigue Syndrome (CFS), fibromyalgia, irritable bowel syndrome, multiple chemical sensitivity, and Gulf War illness (GWI), and subsets of autism spectrum disorder (ASD). GWI entails a more circumscribed set of experiences that may provide insights of relevance to overlapping conditions.
Objectives: To consolidate evidence regarding a role for oxidative stress and mitochondrial dysfunction (OSMD), as primary mediators in CMI, using GWI as a departure point.
Methods: Exposure relations, character, timecourse and multiplicity of symptoms, and objective correlates of GWI are compared to expectation for OSMD. Objective correlates of OSMD in GWI and overlapping conditions are examined. 
Discussion: OSMD is an expected consequence of known GWI exposures; is compatible with symptom characteristics observed; and accords with objective markers and health conditions linked to GWI, extending to autoimmune disease and infection. Emergent triangulating evidence directly supports OSMD in multisymptom “overlap” CMI conditions, with similarities to, and diagnosed at elevated rates in, GWI, suggesting a common role in each. 
Conclusions: GWI is compatible with a paradigm by which uncompensated exposure to oxidative/nitrative stressors accompanies and triggers mitochondrial dysfunction, cell energy compromise, and multiple downstream effects such as vulnerability to autoantibodies. This promotes a profile of protean symptoms with variable latency emphasizing but not confined to energy-demanding post-mitotic tissues, according with (and accounting for) known properties of multisystem overlap conditions. This advances understanding of GWI; health conditions attending GWI at elevated rates; and overlap conditions like CFS and ASD, providing prospects for vulnerability assessment, mitigation of progression, treatment, and future prevention – with implications germane to additive and excessive environmental oxidative stressor exposures in the civilian setting.

