Enabling Accessibility Through Model-Based User Interface Development.

Adaptive user interfaces (AUIs) can increase the accessibility of interactive systems. They provide personalized display and interaction modes to fit individual user needs. Most AUI approaches rely on model-based development, which is considered relatively demanding. This paper explores strategies to make model-based development more attractive for mainstream developers.

Use of Transcranial Doppler in Patients with Severe Traumatic Brain Injuries.

Severe traumatic brain injuries (TBI) are associated with a high rate of mortality and disability. Transcranial Doppler (TCD) sonography permits a noninvasive measurement of cerebral blood flow. The purpose of this study is to determine the usefulness of TCD in patients with severe TBI. TCD was performed, from April 2008 to April 2013, on 255 patients with severe TBI, defined as a Glasgow Coma Scale score of ≤8 on admission. TCD was performed on hospital days 1, 2, 3, and 7. Hypoperfusion was defined by having two out of three of the following: 1) mean velocity (Vm) of the middle cerebral artery <35 cm/sec, 2) diastolic velocity (Vd) of the middle cerebral artery <20 cm/sec, or 3) pulsatility index (PI) of >1.4. Vasospasm was defined by the following: Vm of the middle cerebral artery >120 cm/sec and/or a Lindegaard index (LI) >3. One hundred fourteen (45%) had normal measurements. Of these, 92 (80.7%) had a good outcome, 6 (5.3%) had moderate disability, and 16 (14%) died, 4 from brain death. Seventy-two patients (28%) had hypoperfusion and 71 (98.6%) died, 65 from brain death, and 1 patient survived with moderate disability. Sixty-nine patients (27%) had vasospasm, 31 (44.9%) had a good outcome, 16 (23.2%) had severe disability, and 22 (31.9%) died, 13 from brain death. The vasospasm was detected on hospital day 1 in 8 patients, on day 2 in 23 patients, on day 3 in 22 patients, and on day 7 in 16 patients. Patients with normal measurements can be expected to survive. Patients with hypoperfusion have a poor prognosis. Patients with vasospasm have a high incidence of mortality and severe disability. TCD is useful in determining early prognosis.

Catalytic Enantioselective Carbon-Oxygen Bond Formation: Phosphine-Catalyzed Synthesis of Benzylic Ethers via the Oxidation of Benzylic C-H Bonds.

Benzylic alcohols and ethers are common subunits in bioactive molecules, as well as useful intermediates in organic chemistry. In this Communication, we describe a new approach to the enantioselective synthesis of benzylic ethers through the chiral phosphine-catalyzed coupling of two readily available partners, γ-aryl-substituted alkynoates and alcohols, under mild conditions. In this process, the alkynoate partner undergoes an internal redox reaction. Specifically, the benzylic position is oxidized with good enantioselectivity, and the alkyne is reduced to the alkene.

Direct Access to ß-Fluorinated Aldehydes by Nitrite-Modified Wacker Oxidation.

An aldehyde-selective Wacker-type oxidation of allylic fluorides proceeds with a nitrite catalyst. The method represents a direct route to prepare ß-fluorinated aldehydes. Allylic fluorides bearing a variety of functional groups are transformed in high yield and very high regioselectivity. Additionally, the unpurified aldehyde products serve as versatile intermediates, thus enabling access to a diverse array of fluorinated building blocks. Preliminary mechanistic investigations suggest that inductive effects have a strong influence on the rate and regioselectivity of the oxidation.

Biphenyl-derived phosphepines as chiral nucleophilic catalysts: enantioselective [4+1] annulations to form functionalized cyclopentenes.

Because of the frequent occurrence of cyclopentane subunits in bioactive compounds, the development of efficient catalytic asymmetric methods for their synthesis is an important objective. Introduced herein is a new family of chiral nucleophilic catalysts, biphenyl-derived phosphepines, and we apply them to an enantioselective variant of a useful [4+1] annulation. A range of one-carbon coupling partners can be employed, thereby generating cyclopentenes which bear a fully substituted stereocenter [either all-carbon or heteroatom-substituted (sulfur and phosphorus)]. Stereocenters at the other four positions of the cyclopentane ring can also be introduced with good stereoselectivity. An initial mechanistic study indicates that phosphine addition to the electrophilic four-carbon coupling partner is not the turnover-limiting step of the catalytic cycle.

A versatile approach to Ullmann C-N couplings at room temperature: new families of nucleophiles and electrophiles for photoinduced, copper-catalyzed processes.

The use of light to facilitate copper-catalyzed cross-couplings of nitrogen nucleophiles can enable C-N bond formation to occur under unusually mild conditions. In this study, we substantially expand the scope of such processes, establishing that this approach is not limited to reactions of carbazoles with iodobenzene and alkyl halides. Specifically, we demonstrate for the first time that other nitrogen nucleophiles (e.g., common pharmacophores such as indoles, benzimidazoles, and imidazoles) as well as other electrophiles (e.g., hindered/deactivated/heterocyclic aryl iodides, an aryl bromide, an activated aryl chloride, alkenyl halides, and an alkynyl bromide) serve as suitable partners. Photoinduced C-N bond formation can be achieved at room temperature using a common procedure with an inexpensive catalyst (CuI) that does not require a ligand coadditive and is tolerant of moisture and a variety of functional groups.

Cortisol changes among patients with septic shock and the relationship to ICU and hospital stay.

OBJECTIVE: To evaluate adrenal function in patients with severe sepsis or septic shock. DESIGN: A prospective study of unstimulated and high-dose ACTH stimulated cortisol levels on days 1 and 2 following ICU admission and day 28 or last day of hospitalization (herein day 28). SETTING: General intensive care unit. PATIENTS: 34 septic patients. INTERVENTIONS: On days 1, 2, and 28 of sepsis unstimulated and ACTH stimulated cortisol levels were evaluated. End-points were length of ICU and hospital stay and 28 day all cause mortality. MEASUREMENTS AND RESULTS: Eight patients on days 1 and 2 had criteria of adrenal insufficiency defined as unstimulated cortisol levels less than 15 microg/dl. Patients with unstimulated cortisol levels less than 15 microg/dl on day 1 or change of 9 microg/dl or less had longer ICU stays. Patients with unstimulated cortisol levels less than 15 microg/dl on day 1 also demonstrated longer hospital stay. On day 1 regression analysis revealed that unstimulated cortisol levels had a significant inverse correlation with length of ICU and hospital stay. The proportional change between unstimulated cortisol and post-ACTH cortisol (Delta%) is a new modality; the higher this Delta% value, the longer is the patient's ICU and hospital stay. A significant positive correlation was found in survivors when comparing unstimulated cortisol vs. day 28 changes. CONCLUSIONS: The present study highlights the wide range of cortisol levels among patients with sepsis. We observed a difference in cortisol response pattern between survivors and nonsurvivors on day 28. The proportional change between unstimulated cortisol and post-ACTH cortisol was used as a method to evaluate the relative change in cortisol levels between patients.

Anger and the ABC model underlying Rational-Emotive Behavior Therapy.

The ABC model underlying Ellis's Rational-Emotive Behavior Therapy predicts that people who think more irrationally should display greater trait anger than do people who think less irrationally. This study tested this prediction regarding the ABC model. 186 college students were administered the Survey of Personal Beliefs and the State-Trait Anger Expression Inventory-Second Edition to measure irrational thinking and trait anger, respectively. Students who scored higher on Overall Irrational Thinking and Low Frustration Tolerance scored significantly higher on Trait Anger than did those who scored lower on Overall Irrational Thinking and Low Frustration Tolerance. This indicates support for the ABC model, especially Ellis's construct of irrational beliefs which is central to the model.

A test of the ABC model underlying rational emotive behavior therapy.

The ABC model underlying Ellis's Rational Emotive Behavior Therapy predicts that people who think more irrationally should respond to daily stressors or hassles differently than do people who think less irrationally. This study tested this aspect of the ABC model. 192 college students were administered the Survey of Personal Beliefs and the Hassles Scale to measure irrational thinking and daily hassles, respectively. Students who scored higher on overall irrational thinking reported a significantly higher frequency of hassles than did those who scored lower on overall irrational thinking, while students who scored higher on awfulizing and low frustration tolerance reported a significantly greater intensity of hassles than did those who scored lower on awfulizing and low frustration tolerance. This indicates support for the ABC model, especially Ellis's construct of irrational beliefs central to this model.

An overview of the mechanism, substrate specificities, and structure of FMOs.

Kinetic studies carried out over the past three decades, primarily with purified pig liver flavin-containing monooxygenase (FMO1), demonstrated that the mechanism of this flavoenzyme was distinctly different from other widely studied flavin-dependent monooxygenases in that reduction of O2 by nicotinamide-adenine-dinucleotide-phosphate reduced (NADPH) occurred before the addition of the xenobiotic substrate. Compounds bearing a soft nucleophilic heteroatom show substrate activity provided they could contact the enzyme-bound 4a-hydroperoxy flavin. Structure-activity studies suggest that in addition to nucleophilicity, size and charge of potential substrates are important parameters limiting access to the enzyme-bound hydroxylating intermediate form of the enzyme. The mechanism of FMO 1, 2, 3, and 4 are similar and differences in the substrate specificities of these isoforms can be attributed almost entirely to differences in the dimensions of the cleft or channel limiting access to the 4a-hydroperoxy flavin. While this model provides a satisfactory mechanism for the FMO catalyzed oxidation of very soft nucleophiles, it does not address another very important element of the catalytic cycle. The amine nitrogen atom is not an especially soft nucleophile readily hydroxylated by peroxides or peracids. How the enzymes convert an amine substrate to a form readily attacked by the hydroperoxy flavin is presently unknown. A complete resolution of this problem will only be possible after the tertiary structures of these enzymes are solved.