Chronic lymphocytic leukemia and the central nervous system: a clinical and pathological study.

Chronic lymphocytic leukemia is the most common human leukemia but infrequently causes neurologic symptoms. We have reviewed all previously reported cases of chronic lymphocytic leukemia in the CNS along with three new cases; one patient was diagnosed antemortem and treated with immediate improvement and 4-year survival. In addition, we reviewed all autopsy cases since 1972 and available lumbar puncture data on patients with chronic lymphocytic leukemia admitted to the Massachusetts General Hospital. Invasion of the CNS by chronic lymphocytic leukemia often leads to confusional state, meningitis with cranial nerve abnormalities, optic neuropathy, or cerebellar dysfunction. Lumbar puncture shows a lymphocytosis consisting of monoclonal B cells, but CSF cytology studies are of limited value in establishing the diagnosis. Long-term survival may be related to the stage of chronic lymphocytic leukemia at the time of CNS disease and may be associated with intrathecal chemotherapy. A mild, asymptomatic infiltration of the brain, frequently noted in late-stage chronic lymphocytic leukemia in autopsy series, may explain the CSF lymphocytosis in some patients with late-stage chronic lymphocytic leukemia

Characteristics of C-4 photosynthesis in stems and petioles of C-3 flowering plants

Most plants are known as C-3 plants because the first product of photosynthetic CO2 fixation is a three-carbon compound. C-4 plants, which use an alternative pathway in which the first product is a four-carbon compound, have evolved independently many times and are found in at least 18 families. In addition to differences in their biochemistry, photosynthetic organs of C-4 plants show alterations in their anatomy and ultrastructure. Little is known about whether the biochemical or anatomical characteristics of C-4 photosynthesis evolved first. Here we report that tobacco, a typical C-3 plant, shows characteristics of C-4 photosynthesis in cells of stems and petioles that surround the xylem and phloem, and that these cells are supplied with carbon for photosynthesis from the vascular system and not from stomata. These photosynthetic cells possess high activities of enzymes characteristic of C-4 photosynthesis, which allow the decarboxylation of four-carbon organic acids from the xylem and phloem, thus releasing CO2 for photosynthesis. These biochemical characteristics of C-4 photosynthesis in cells around the vascular bundles of stems of C-3 plants might explain why C-4 photosynthesis has evolved independently many times

Final report on the evaluation of the RAC input data elements.

The Resource Allocation Criteria (RAC) began to develop in 1972, responding to management requirements of the Indian Health Service (IHS). The RAC is now the principal management tool of the IHS Manpower Management Program, which justifies all manpower-related budgetary requests to the Department of Health and Human Services (DHHS). RAC fulfills its obligations by identifying necessary tasks to provide quality resources for each segment of the health care system. The purpose of this study was to determine the reliability of the data inputs to RAC, the degree to which the quality of the input affects the reliability of the output. and Identification of means to improve the quality of input data. The study first identified input data elements through the use of archival (RAC) records and interviews with IHS personnel. From this data, flow charts and profile sheets were compiled. IHS Program/Area Offices site visits were then initiated. Here, patient records were sampled, meetings with site personnel to review methods in use were held, and local finance and contract personnel were interviewed to determine volume of and tracking method for services. Using these data, flow charts were developed and data estimates were constructed using all previously gathered material. From these data estimates, the accuracy of RAC input data was compared with the actual data collected and the constructed data estimates. The findings of the study included: 1) as a result of perceived undercounting, population data from IHS suffers from a lack of confidence at the Area Offices; 2) both inpatient and outpatient data are suspect because of the practice of issuing one patient more than one patient number and, conversely issuing the same patient number to more than one patient; 3) illegible record entries hinder accurate patient data gathering; 4) a high turnover in record keeping personnel; 5) a significantly lower error rate in inpatient data than in outpatient data; 6) a number of inpatient and outpatient records never enter the IHS data system; 7) alcoholism is not always reported as the cause of medical attention in projecting demand for contract health services; 8) RAC does not adequately project the additional need for P.L. 638 contracting; 9) data is often lacking from HSA-43 and HSA-64 reporting forms; 10) contract health service providers are not always audited; 11) many contract service bills are submitted after the close of the fiscal year; 12) RAC staffing tables are relatively insensitive from a statistical perspective; and 13) Service Units and Area Offices are more accurate predictors of direct service needs than are contract providers. Numerous recommendations are made concerning: 1) the national decennial census; 2) population migration and projections; 3) a unique patient identification numbering system; 4) inpatient and outpatient data verification procedures; 5) feasibility of developing the HSA-44-1 and the HSA-406 as clinical management tools; 6) an inventory of the patient record system; 7) Area Offices review systems checks; 8) the accuracy of patient data; 9) use of HSA-406 forms during itinerant visits; 10) a training program for Community Health Aides (CHAs); 11) reporting alcoholism as a primary diagnosis; 12) projected utilization of contract services to actual contract services needs; 13) a method of identifying and projecting P.L. 638 costs; 14) efforts to obtain all contractor invoices before the end of the fiscal year; 15) algorithms that support staffing tables and then perform another sensitivity analysis; and 21) standardization of collection, reporting, and recording parameters of projected and actual data and ensure a consistent application in developing RAC input data

End-to-end verifiable elections in the standard model

We present the cryptographic implementation of “DEMOS”, a new e-voting system that is end-to-end verifiable in the standard model, i.e., without any additional “setup” assumption or access to a random oracle (RO). Previously known end-to-end verifiable e-voting systems required such additional assumptions (specifically, either the existence of a “randomness beacon” or were only shown secure in the RO model). In order to analyze our scheme, we also provide a modeling of end-to-end verifiability as well as privacy and receipt-freeness that encompasses previous definitions in the form of two concise attack games. Our scheme satisfies end-to-end verifiability information theoretically in the standard model and privacy/receipt-freeness under a computational assumption (subexponential Decisional Diffie Helman). In our construction, we utilize a number of techniques used for the first time in the context of e-voting schemes that include utilizing randomness from bit-fixing sources, zero-knowledge proofs with imperfect verifier randomness and complexity leveraging

Round-Optimal Secure Two-Party Computation from Trapdoor Permutations

In this work we continue the study on the round complexity of secure two-party computation with black-box simulation. Katz and Ostrovsky in CRYPTO 2004 showed a 5 (optimal) round construction assuming trapdoor permutations for the general case where both players receive the output. They also proved that their result is round optimal. This lower bound has been recently revisited by Garg et al. in Eurocrypt 2016 where a 4 (optimal) round protocol is showed assuming a simultaneous message exchange channel. Unfortunately there is no instantiation of the protocol of Garg et al. under standard polynomial-time hardness assumptions. In this work we close the above gap by showing a 4 (optimal) round construction for secure two-party computation in the simultaneous message channel model with black-box simulation, assuming trapdoor permutations against polynomial-time adversaries. Our construction for secure two-party computation relies on a special 4-round protocol for oblivious transfer that nicely composes with other protocols in parallel. We define and construct such special oblivious transfer protocol from trapdoor permutations. This building block is clearly interesting on its own. Our construction also makes use of a recent advance on non-malleability: a delayed-input 4-round non-malleable zero knowledge argument

Systematic assessment of training-induced changes in corticospinal output to hand using frameless stereotaxic transcranial magnetic stimulation.

Measuring changes in the characteristics of corticospinal output has become a critical part of assessing the impact of motor experience on cortical organization in both the intact and injured human brain. In this protocol we describe a method for systematically assessing training-induced changes in corticospinal output that integrates volumetric anatomical MRI with transcranial magnetic stimulation (TMS). A TMS coil is sited to a target grid superimposed onto a 3D MRI of cortex using a stereotaxic neuronavigation system. Subjects are then required to exercise the first dorsal interosseus (FDI) muscle on two different tasks for a total of 30 min. The protocol allows for reliably and repeatedly detecting changes in corticospinal output to FDI muscle in response to brief periods of motor training

Disease acceptance and adherence to imatinib in Taiwanese chronic myeloid leukaemia outpatients

Background The launch of imatinib has turned chronic myeloid leukaemia (CML) into a chronic illness due to the dramatic improvement in survival. Several recent studies have demonstrated that poor adherence to imatinib may hamper the therapeutic outcomes and result in increased medical expenditures, whilst research on exploring the reasons for non-adherence to imatinib is still limited. Objective This study aimed to explore the experience of patients as they journey through their CML treatments and associated imatinib utilisation in order to understand the perceptions, attitudes and concerns that may influence adherence to imatinib treatment. Setting This study was conducted at oncology outpatient clinics in a medical centre in southern Taiwan. Methods CML patients who regularly attended the oncology outpatient clinics to receive imatinib treatment from October 2011 to March 2012 were invited to participate in the study. Semi-structured face-to-face interviews were used to explore patients’ experiences and views of their treatment, their current CML status and CML-related health conditions, their concerns about imatinib treatment and imatinib-taking behaviours. Patient interviews were recorded, transcribed verbatim and thematically analysed using the constant comparison approach. Main outcome measure Themes related to patients’ views of the disease and health conditions, worries and concerns influencing imatinib utilisation behaviours are reported. Results Forty-two CML patients participated in the interviews. The emerging themes included: acceptance of current disease and health status, misconceptions about disease progression, factors associated with adherence to imatinib, concerns and management of adverse drug effects. Participants regarded CML as a chronic disease but had misconceptions about disease progression, therapeutic monitoring, resistance to imatinib and symptoms of side effects. Participants were generally adherent to imatinib and favoured long-term prescriptions to avoid regular outpatient visits for medication refills. Experiencing adverse effect was the main reason influencing adherence and led to polypharmacy. Most participants altered medicine-taking behaviours to maintain long-term use of imatinib. Conclusion Taiwanese CML patients are adherent to imatinib but report changing their medication-taking behaviour due to adverse drug effects and associated polypharmacy. Patients’ misconceptions of the disease and medication suggests that it is necessary to improve communication between patients and healthcare professionals. Routinely providing updated information as part of the patient counselling process should be considered as a means of improving this communication

Mouse models for preeclampsia: disruption of redox-regulated signaling

The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD

Online/Offline OR Composition of Sigma Protocols

Proofs of partial knowledge allow a prover to prove knowledge of witnesses for k out of n instances of NP languages. Cramer, Schoenmakers and Damgård [10] provided an efficient construction of a 3-round public-coin witness-indistinguishable (k, n)-proof of partial knowledge for any NP language, by cleverly combining n executions of Σ-protocols for that language. This transform assumes that all n instances are fully specified before the proof starts, and thus directly rules out the possibility of choosing some of the instances after the first round. Very recently, Ciampi et al. [6] provided an improved transform where one of the instances can be specified in the last round. They focus on (1, 2)-proofs of partial knowledge with the additional feature that one instance is defined in the last round, and could be adaptively chosen by the verifier. They left as an open question the existence of an efficient (1, 2)-proof of partial knowledge where no instance is known in the first round. More in general, they left open the question of constructing an efficient (k, n)-proof of partial knowledge where knowledge of all n instances can be postponed. Indeed, this property is achieved only by inefficient constructions requiring NP reductions [19]. In this paper we focus on the question of achieving adaptive-input proofs of partial knowledge. We provide through a transform the first efficient construction of a 3-round public-coin witness-indistinguishable (k, n)-proof of partial knowledge where all instances can be decided in the third round. Our construction enjoys adaptive-input witness indistinguishability. Additionally, the proof of knowledge property remains also if the adversarial prover selects instances adaptively at last round as long as our transform is applied to a proof of knowledge belonging to the widely used class of proofs of knowledge described in [9,21]. Since knowledge of instances and witnesses is not needed before the last round, we have that the first round can be precomputed and in the online/offline setting our performance is similar to the one of [10]. Our new transform relies on the DDH assumption (in contrast to the transforms of [6,10] that are unconditional)

Change of initial oral antidiabetic therapy in type 2 diabetic patients

Objective To explore the 'real-life' therapy of type 2 diabetes mellitus with oral antidiabetic drugs (OADs). Methods From the PHARMO Record Linkage System comprising linked drug dispensing and clinical laboratory data from approximately 2.5 million individuals in the Netherlands, among others, new users of OADs were identified in the period 1999-2004. New users, aged 30 years and older, without insulin use before cohort entry date and with at least one year follow-up were included. We determined per initial therapy patient characteristics and first therapy change. Results Overall 35,514 patients were included. Metformin and sulfonylureas (SU) were the most frequent initial therapy. Patients on thiazolidinedione (TZD) monotherapy had lower percentages baseline HbA1c ≥ 7% compared to patients on metformin and SU. The proportion of patients still on initial therapy after one year ranged from 46% (TZDs) to around 60% (SU). Among patients starting on monotherapy, add-on (15-20%) and discontinuation (16-25%) of therapy occurred most frequently. In patients starting on combination therapy, a switch occurred in 30% of the patients. Conclusion In more than 40% of the patients a change in initial OAD-therapy is already observed in the first year of therapy. Maintaining patients on initial therapy remains a challenge