Cellular immunophenotypic studies were performed on a cohort of randomly selected IgM(+) B-chronic lymphocytic leukemia (B-CLL) cases for which Ig V(H) and V(L) gene sequences were available. The ...cases were categorized based on V gene mutation status and CD38 expression and analyzed for treatment history and survival. The B-CLL cases could be divided into 2 groups. Those patients with unmutated V genes displayed higher percentages of CD38(+) B-CLL cells (>/=30%) than those with mutated V genes that had lower percentages of CD38(+) cells (<30%). Patients in both the unmutated and the >/=30% CD38(+) groups responded poorly to continuous multiregimen chemotherapy (including fludarabine) and had shorter survival. In contrast, the mutated and the <30% CD38(+) groups required minimal or no chemotherapy and had prolonged survival. These observations were true also for those patients who stratified to the Rai intermediate risk category. In the mutated and the <30% CD38(+) groups, males and females were virtually equally distributed, whereas in the unmutated and the >/=30% CD38(+) groups, a marked male predominance was found. Thus, Ig V gene mutation status and the percentages of CD38(+) B-CLL cells appear to be accurate predictors of clinical outcome in B-CLL patients. These parameters, especially CD38 expression that can be analyzed conveniently in most clinical laboratories, should be valuable adjuncts to the present staging systems for predicting the clinical course in individual B-CLL cases. Future evaluations of new therapeutic strategies and drugs should take into account the different natural histories of patients categorized in these manners.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We report a monomeric yellow-green fluorescent protein, mNeonGreen, derived from a tetrameric fluorescent protein from the cephalochordate Branchiostoma lanceolatum. mNeonGreen is the brightest ...monomeric green or yellow fluorescent protein yet described to our knowledge, performs exceptionally well as a fusion tag for traditional imaging as well as stochastic single-molecule superresolution imaging and is an excellent fluorescence resonance energy transfer (FRET) acceptor for the newest cyan fluorescent proteins.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Understanding space-charge-limited current density (SCLCD) is fundamentally and practically important for characterizing many high-power and high-current vacuum devices. Despite this, no analytic ...equations for SCLCD with nonzero monoenergetic initial velocity have been derived for nonplanar diodes from first principles. Obtaining analytic equations for SCLCD for nonplanar geometries is often complicated by the nonlinearity of the problem and over constrained boundary conditions. In this Letter, we use the canonical coordinates obtained by identifying Lie-point symmetries to linearize the governing differential equations to derive SCLCD for any orthogonal diode. Using this method, we derive exact analytic equations for SCLCD with a monoenergetic injection velocity for one-dimensional cylindrical, spherical, tip-to-tip (t-t), and tip-to-plate (t-p) diodes. We specifically demonstrate that the correction factor from zero initial velocity to monoenergetic emission depends only on the initial kinetic and electric potential energies and not on the diode geometry and that SCLCD is universal when plotted as a function of the canonical gap size. We also show that SCLCD for a t-p diode is a factor of four larger than a t-t diode independent of injection velocity. The results reduce to previously derived results for zero initial velocity using variational calculus and conformal mapping.
Full text
Available for:
CMK, CTK, FMFMET, IJS, NUK, PNG, UM
B-cell chronic lymphocytic leukemia (B-CLL) is considered an accumulative disease of antigen-naive CD5+ B lymphocytes that circulate in the resting state. However, to evaluate the possibility that ...B-CLL cells resemble antigen-experienced and activated B cells, we analyzed the expression of markers of cellular activation and differentiation on CD5+CD19+ cells from B-CLL patients and from age-matched healthy donors. The leukemic cells from all B-CLL patients, including those that lack significant numbers of V gene mutations, bear the phenotype of activated B cells based on the overexpression of the activation markers CD23, CD25, CD69, and CD71 and the underexpression of CD22, Fcγ receptor IIb, CD79b, and immunoglobulin D that are down-regulated by cell triggering and activation. Furthermore, these leukemic cells resemble antigen-experienced lymphocytes in the underexpression of molecules that are down-regulated by cell triggering and in the uniform expression of CD27, an identifier of memory B cells. A comparison of the phenotypes of B-CLL patients with and without immunoglobulin V gene mutations suggests that the 2 subgroups differ both in specific marker expression (CD69, CD71, CD62 L, CD40, CD39, and HLA-DR) and in the time since antigenic stimulation, based on the reciprocal relationship of CD69 and CD71 expression. These findings imply that the leukemic cells from all B-CLL cases (irrespective of V gene mutations) exhibit features of activated and of antigen-experienced B lymphocytes and that the B-CLL cells that differ in immunoglobulin V genotype may have different antigen-encounter histories.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Newly developed achromatic electron optics allows the use of wide energy windows and makes feasible energy-filtered transmission electron microscopy (EFTEM) at atomic resolution. In this Letter we ...present EFTEM images formed using electrons that have undergone a silicon L(2,3) core-shell energy loss, exhibiting a resolution in EFTEM of 1.35 Å. This permits elemental mapping beyond the nanoscale provided that quantum mechanical calculations from first principles are done in tandem with the experiment to understand the physical information encoded in the images.
Full text
Available for:
CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Recruitment overfishing occurs when stocks are fished to a level where recruitment declines proportionally with adult abundance. Although typically considered a commercial fishery problem, ...recruitment overfishing can also occur in freshwater recreational fisheries. This study developed an age‐structured model to determine if minimum‐length limits can prevent recruitment overfishing in black crappie, Pomoxis nigromaculatus (LeSueur), and walleye, Sander vitreus (Mitchill) fisheries considering angling effort response to changes in fish abundance. Simulations showed that minimum‐length limits prevented recruitment overfishing of black crappie and walleye, but larger minimum‐length limits were required if angler effort showed only weak responses to changes in fish abundance. Low angler‐effort responsiveness caused fishing mortality rates to remain high when stock abundance declined. By contrast, at high effort responsiveness, anglers left the fishery in response to stock declines and allowed stocks to recover. Angler effort for black crappie and walleye fisheries suggested that angler effort could be highly responsive for some fisheries and relatively stable for others, thereby increasing the risk of recruitment overfishing in real fisheries. Recruitment overfishing should be considered seriously in freshwater recreational fisheries, and more studies are needed to evaluate the responsiveness of angler effort to changes in fish abundance.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract Objectives To identify and evaluate screening tools that have been used in heart failure (HF), and determine their usefulness and feasibility in the clinical setting. Background There is ...increasing evidence that HF is associated with a pattern of cognitive impairment (CI) characterized by subtle deficits particularly in the domains of memory, attention, and executive function with increasing evidence of mild cognitive impairment (MCI). A standard, effective CI screening measure for HF has not been identified. Methods A review of the literature published from January 2000 to May 2011 was conducted to identify studies that used one or more screening instrument to identify or describe CI in HF. Results Seven screening instruments were identified across the 23 studies reviewed. The screening approaches vary in length, cut points, scoring methods, and cognitive domains covered. Conclusions The Mini Mental State Exam is the most frequently used screening measure, but does not appear to be an adequate instrument to detect the type of cognitive impairment seen in HF. Combining instruments such as the Clock Drawing test with the Abbreviated Mental test would screen for deficits in the appropriate cognitive domains. The Montreal Cognitive Assessment is more comprehensive and appears to be a suitable screening tool for HF. A standard, brief, sensitive screening instrument designed to detect subtle cognitive impairment in the areas of attention, memory, executive function, and psychomotor speed should be adopted for use in HF.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective To evaluate whether race or ethnicity was independently associated with parental refusal of consent for their child's participation in a multisite pediatric critical care clinical trial. ...Study design We performed a secondary analyses of data from Randomized Evaluation of Sedation Titration for Respiratory Failur e (RESTORE), a 31-center cluster randomized trial of sedation management in critically ill children with acute respiratory failure supported on mechanical ventilation. Multivariable logistic regression modeling estimated associations between patient race and ethnicity and parental refusal of study consent. Result Among the 3438 children meeting enrollment criteria and approached for consent, 2954 had documented race/ethnicity of non-Hispanic White (White), non-Hispanic Black (Black), or Hispanic of any race. Inability to approach for consent was more common for parents of Black (19.5%) compared with White (11.7%) or Hispanic children (13.2%). Among those offered consent, parents of Black (29.5%) and Hispanic children (25.9%) more frequently refused consent than parents of White children (18.2%, P < .0167 for each). Compared with parents of White children, parents of Black (OR 2.15, 95% CI 1.56-2.95, P < .001) and Hispanic (OR 1.44, 95% CI 1.10-1.88, P = .01) children were more likely to refuse consent. Parents of children offered participation in the intervention arm were more likely to refuse consent than parents in the control arm (OR 2.15, 95% CI 1.37-3.36, P < .001). Conclusions Parents of Black and Hispanic children were less likely to be approached for, and more frequently declined consent for, their child's participation in a multisite critical care clinical trial. Ameliorating this racial disparity may improve the validity and generalizability of study findings. Trial registration ClinicalTrials.gov : NCT00814099.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
PDF
