Translation into Spanish and field-testing of a new score for evaluating psoriasis severity: The Simplified Psoriasis Index (SPI). / Traducción al español y ensayos de campo de una nueva escala destinada a la valoración global de la gravedad de la psoriasis: el índice de psoriasis simplificado (SPI).

BACKGROUND: The simplified psoriasis index (SPI) was developed in the United Kingdom to provide a simple summary measure for monitoring changes in psoriasis severity and associated psychosocial impact as well as for obtaining information about past disease behavior and treatment. Two complementary versions of the SPI allow for self-assessment by the patient or professional assessment by a doctor or nurse. Both versions have proven responsive to change, reliable, and interpretable, and to correlate well with assessment tools that are widely used in clinical trials - the Psoriasis Area and Severity Index and the Dermatology Quality of Life Index. The SPI has already been translated into several languages, including French, Brazilian Portuguese, Dutch, Arabic, and Thai. OBJECTIVE: To translate the professional and self-assessment versions of the SPI to Spanish and to field test the translations. METHOD: A medically qualified native Spanish speaker translated both versions of the SPI into Spanish. The Spanish translations were discussed by comparing them to blinded back translations into English undertaken by native English speakers; the Spanish texts were then revised in an iterative process involving the translators, 4 dermatologists, and 20 patients. The patients scored their own experience of psoriasis with the self-assessment version and commented on it. The process involved checking the conceptual accuracy of the translation, language-related differences, and subtle gradations of meaning in a process involving all translators and a panel of both Spanish- and English-speaking dermatologists, including a coauthor of the SPI. RESULTS: The final self-assessment and professional Spanish versions of the SPI are presented in this manuscript. CONCLUSIONS: Castilian Spanish translations of both versions of the SPI are now available for monitoring disease changes in Spanish-speaking patients with psoriasis under routine clinical care.

Broadband, millimeter-wave antireflection coatings for large-format, cryogenic aluminum oxide optics.

We present two prescriptions for broadband ($ {\sim} 77 - 252\;{\rm GHz} $), millimeter-wave antireflection coatings for cryogenic, sintered polycrystalline aluminum oxide optics: one for large-format (700 mm diameter) planar and plano-convex elements, the other for densely packed arrays of quasi-optical elements-in our case, 5 mm diameter half-spheres (called "lenslets"). The coatings comprise three layers of commercially available, polytetrafluoroethylene-based, dielectric sheet material. The lenslet coating is molded to fit the 150 mm diameter arrays directly, while the large-diameter lenses are coated using a tiled approach. We review the fabrication processes for both prescriptions, then discuss laboratory measurements of their transmittance and reflectance. In addition, we present the inferred refractive indices and loss tangents for the coating materials and the aluminum oxide substrate. We find that at 150 GHz and 300 K the large-format coating sample achieves $ (97 \pm 2)\% $ transmittance, and the lenslet coating sample achieves $ (94 \pm 3)\% $ transmittance.

Detection of CMB-Cluster Lensing using Polarization Data from SPTpol.

We report the first detection of gravitational lensing due to galaxy clusters using only the polarization of the cosmic microwave background (CMB). The lensing signal is obtained using a new estimator that extracts the lensing dipole signature from stacked images formed by rotating the cluster-centered Stokes QU map cutouts along the direction of the locally measured background CMB polarization gradient. Using data from the SPTpol 500 deg^{2} survey at the locations of roughly 18 000 clusters with richness λ≥10 from the Dark Energy Survey (DES) Year-3 full galaxy cluster catalog, we detect lensing at 4.8σ. The mean stacked mass of the selected sample is found to be (1.43±0.40)×10^{14}M_{⊙} which is in good agreement with optical weak lensing based estimates using DES data and CMB-lensing based estimates using SPTpol temperature data. This measurement is a key first step for cluster cosmology with future low-noise CMB surveys, like CMB-S4, for which CMB polarization will be the primary channel for cluster lensing measurements.

New Results from the Search for Low-Mass Weakly Interacting Massive Particles with the CDMS Low Ionization Threshold Experiment.

The CDMS low ionization threshold experiment (CDMSlite) uses cryogenic germanium detectors operated at a relatively high bias voltage to amplify the phonon signal in the search for weakly interacting massive particles (WIMPs). Results are presented from the second CDMSlite run with an exposure of 70 kg day, which reached an energy threshold for electron recoils as low as 56 eV. A fiducialization cut reduces backgrounds below those previously reported by CDMSlite. New parameter space for the WIMP-nucleon spin-independent cross section is excluded for WIMP masses between 1.6 and 5.5 GeV/c^{2}.

First direct limits on lightly ionizing particles with electric charge less than e/6.

While the standard model of particle physics does not include free particles with fractional charge, experimental searches have not ruled out their existence. We report results from the Cryogenic Dark Matter Search (CDMS II) experiment that give the first direct-detection limits for cosmogenically produced relativistic particles with electric charge lower than e/6. A search for tracks in the six stacked detectors of each of two of the CDMS II towers finds no candidates, thereby excluding new parameter space for particles with electric charges between e/6 and e/200.

Search for low-mass weakly interacting massive particles using voltage-assisted calorimetric ionization detection in the SuperCDMS experiment.

SuperCDMS is an experiment designed to directly detect weakly interacting massive particles (WIMPs), a favored candidate for dark matter ubiquitous in the Universe. In this Letter, we present WIMP-search results using a calorimetric technique we call CDMSlite, which relies on voltage-assisted Luke-Neganov amplification of the ionization energy deposited by particle interactions. The data were collected with a single 0.6 kg germanium detector running for ten live days at the Soudan Underground Laboratory. A low energy threshold of 170 eVee (electron equivalent) was obtained, which allows us to constrain new WIMP-nucleon spin-independent parameter space for WIMP masses below 6 GeV/c2.

Search for low-mass weakly interacting massive particles with SuperCDMS.

We report a first search for weakly interacting massive particles (WIMPs) using the background rejection capabilities of SuperCDMS. An exposure of 577 kg days was analyzed for WIMPs with mass <30 GeV/c(2), with the signal region blinded. Eleven events were observed after unblinding. We set an upper limit on the spin-independent WIMP-nucleon cross section of 1.2×10(-42) cm(2) at 8 GeV/c(2). This result is in tension with WIMP interpretations of recent experiments and probes new parameter space for WIMP-nucleon scattering for WIMP masses <6 GeV/c(2).

Silicon detector dark matter results from the final exposure of CDMS II.

We report results of a search for weakly interacting massive particles (WIMPS) with the silicon detectors of the CDMS II experiment. This blind analysis of 140.2 kg day of data taken between July 2007 and September 2008 revealed three WIMP-candidate events with a surface-event background estimate of 0.41(-0.08)(+0.20)(stat)(-0.24)(+0.28)(syst). Other known backgrounds from neutrons and 206Pb are limited to <0.13 and <0.08 events at the 90% confidence level, respectively. The exposure of this analysis is equivalent to 23.4 kg day for a recoil energy range of 7-100 keV for a WIMP of mass 10 GeV/c2. The probability that the known backgrounds would produce three or more events in the signal region is 5.4%. A profile likelihood ratio test of the three events that includes the measured recoil energies gives a 0.19% probability for the known-background-only hypothesis when tested against the alternative WIMP+background hypothesis. The highest likelihood occurs for a WIMP mass of 8.6 GeV/c2 and WIMP-nucleon cross section of 1.9×10(-41) cm2.

Production of the antifungal compounds phenazine and pyrrolnitrin from Pseudomonas chlororaphis O6 is differentially regulated by glucose.

AIMS: To determine whether glucose in growth medium affects secondary metabolite production and biocontrol efficacy of Pseudomonas chlororaphis O6. METHODS AND RESULTS: The secondary metabolites pyrrolnitrin and phenazines antagonize phytopathogenic fungi. The expression of the prnA gene encoding tryptophan halogenase, the first step in pyrrolnitrin biosynthesis, required the stationary-phase sigma factor, RpoS. Mutations in rpoS and prnA in Ps. chlororaphis O6 eliminated antifungal activity against Rhizoctonia solani and Fusarium graminearum. Pyrrolnitrin production was reduced by glucose in growth media, whereas phenazine levels were increased. The efficacy of Ps. chlororaphis O6 in the biocontrol of tomato late blight was reduced by addition of glucose to the growth medium. CONCLUSIONS: Regulation by glucose of pyrrolnitrin production influenced the efficacy of the biocontrol of tomato leaf blight. SIGNIFICANCE AND IMPACT OF THE STUDY: The nutritional regulation of secondary metabolite production from a soil pseudomonad may account, at least in part, for the variability of biocontrol under field conditions.

A simple two-stage model predicts response time distributions.

The neural mechanisms underlying reaction times have previously been modelled in two distinct ways. When stimuli are hard to detect, response time tends to follow a random-walk model that integrates noisy sensory signals. But studies investigating the influence of higher-level factors such as prior probability and response urgency typically use highly detectable targets, and response times then usually correspond to a linear rise-to-threshold mechanism. Here we show that a model incorporating both types of element in series - a detector integrating noisy afferent signals, followed by a linear rise-to-threshold performing decision - successfully predicts not only mean response times but, much more stringently, the observed distribution of these times and the rate of decision errors over a wide range of stimulus detectability. By reconciling what previously may have seemed to be conflicting theories, we are now closer to having a complete description of reaction time and the decision processes that underlie it.

Copper and cadmium: responses in Pseudomonas putida KT2440.

AIMS: To compare responses of a soil bacterium to Cu and Cd. METHODS AND RESULTS: In minimal medium, Cd caused a dose-dependent growth stasis of logarithmic phase cells of Pseudomonas putida, strain KT2440, whereas Cu did not compromise growth up to 10 mg l(-1). Proteomics showed changes in accumulation of both membrane and soluble proteins by 6 h of treatment; increased Krebs cycle enzymes were apparent. Transcript analysis showed Cd- and Cu-induced different genes. Cd-induced genes encoding the transcriptional regulator CzrR2; an outer membrane protein associated with lipopolysaccharide stability, H1; two oxidative stress protective proteins and the P-type ATPase, CadA2, associated with Cd(2+) efflux. The genes most responsive to Cu encoded the regulator CopR1 and the outer membrane resistance protein regulated by CopR1, CopB1; a putative porin, PorD and the Cu-binding protein, PacZ or CopZ, and CopA2. CONCLUSIONS: These findings support that a soil pseudomonad restricts internalization of the metals by using different sets of binding proteins and efflux pumps. Activation of mechanisms to protect against oxidative stress also was evident especially with Cd exposure. SIGNIFICANCE AND IMPACT OF THE STUDY: The differential cellular responses to Cd and Cu suggest that risk assessment for Cd and Cu should be different.

The effect of stimuli that isolate S-cones on early saccades and the gap effect.

Disappearance of the fixation spot before the appearance of a peripheral target typically reduces average saccadic reaction times (the gap effect) and may also produce a separate population of early or express saccades. The superior colliculus (SC) is generally believed to be critically involved in generating both effects. As the direct sensory input to the SC does not encode colour information, to determine whether this input was critical in generating the gap effect or express saccades we used coloured targets which this pathway cannot distinguish. Our observers still made early saccades to colour-defined targets, but these were anticipations in response to the offset of the non-coloured fixation target. We also show that a gap effect still occurs when either the fixation target or the peripheral target is colour defined, suggesting that direct sensory input to the SC is not required and that information about the location of colour-defined targets is abstracted prior to processing within the SC.

Wheel running and fluoxetine antidepressant treatment have differential effects in the hippocampus and the spinal cord.

Exercise and antidepressants used independently have been shown to increase hippocampal brain-derived neurotrophic factor (BDNF) and neurogenesis. Despite the fact that patients with depression are often prescribed both, the effects of the exercise and fluoxetine antidepressant treatment used in combination are unknown. Using C57Bl/10 female mice, BDNF protein, insulin-like growth factor 1 (IGF-1) protein and neurogenesis were measured in the hippocampus after 21 days of wheel running, 21 days of fluoxetine antidepressant therapy (daily i.p. injections of 5 mg/kg, 10 mg/kg or 25 mg/kg) and the combination of the two. BDNF protein and cytogenesis/neurogenesis increased in the hippocampus with fluoxetine (high dose), but not wheel running. Hippocampal IGF-1 protein did not change with either treatment. There were no synergistic effects of combining exercise and fluoxetine treatment. Recent reports have also shown that exercise induces molecular mechanisms that benefit the spinal cord and can improve recovery after spinal cord injury (SCI); therefore, we repeated the assays in the spinal cord. Results showed that BDNF, IGF-1 and neurogenesis behave independently in the hippocampus and spinal cord. BDNF protein did not change in the spinal cord with either wheel running or fluoxetine treatment. Spinal cord IGF-1 protein did not change with wheel running, but it decreased with fluoxetine (high dose). Furthermore, spinal cord cytogenesis decreased with fluoxetine treatment. The combined wheel running and fluoxetine groups did not show synergistic results. Thus, the hippocampus and the spinal cord respond in distinct ways to wheel running and fluoxetine, and a prior induction of BDNF, IGF-1 or cytogenesis is unlikely to be the mechanism for wheel running providing a margin of protection against SCI.

Pyrene mineralization by Mycobacterium sp. strain KMS in a barley rhizosphere.

To determine whether the soil Mycobacterium isolate KMS would mineralize pyrene under rhizosphere conditions, a microcosm system was established to collect radioactive carbon dioxide released from the labeled polycyclic aromatic hydrocarbon. Microcosms were designed as sealed, flow-through systems that allowed the growth of plants. Experiments were conducted to evaluate mineralization of 14C-labeled pyrene in a sand amended with the polycyclic aromatic hydrocarbons degrading Mycobacterium isolate KMS, barley plants, or barley plants with roots colonized by isolate KMS. Mineralization was quantified by collecting the 14CO2 produced from 14C-labeled pyrene at intervals during the 10-d incubation period. Roots and foliar tissues were examined for 14C incorporation. Mass balances for microcosms were determined through combustion of sand samples and collection and quantification of 14CO2 evolved from radiolabeled pyrene. No pyrene mineralization was observed in the sterile control systems. Greater release of 14CO2 was observed in the system with barley colonized by KMS than in microcosms containing just the bacterium inoculum or sterile barley plants. These findings suggest that phytostimulation of polycyclic aromatic hydrocarbons mineralization could be applied in remediation schemes.

Traumatic occipitocervical disruption: a new technique for stabilisation. Case report and literature review.

Traumatic atlanto-occipital dislocation in adults is usually fatal and survival without neurological deficit is rare. The surgical management of those who do survive is difficult and controversial. Most authorities recommend posterior occipitoaxial fusion, but this compromises cervical rotation. We describe a case in which a patient with a traumatic atlanto-occipital disruption but no neurological deficit was treated by atlanto-occipital fusion using a new technique consisting of cancellous bone autografting supported by an occipital plate linked by rods to lateral mass screws in the atlas. The technique is described in detail. At one year the neck was stable, radiological fusion had been achieved, and atlantoaxial rotation preserved. The rationale behind this approach is discussed and the relevant literature reviewed. We recommend the technique for injuries of this type.

Mitoxantrone in worsening secondary progressive multiple sclerosis: A prospective, open-label study.

BACKGROUND: An antineoplastic agent, mitoxantrone (MX) is used to treat neurologic disability and/or reduce the frequency of clinical relapses in patients with secondary progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (MS). Based on a MEDLINE search for literature concerning the use of IV MX in patients with secondary progressive MS (SPMS), there is a paucity of data to identify the clinical characteristics of responders. OBJECTIVE: The aim of this study was to monitor the effects of IV MX in patients with SPMS and varied clinical characteristics whose condition continued to worsen despite receiving IV methylprednisolone treatment. METHODS: This prospective, open-label study was conducted at the Multiple Sclerosis Clinic, Center for Neurologic Disorders, Milwaukee, Wisconsin. Male and female patients aged ≥18 years with SPMS whose neurologic condition, as assessed using routine neurologic examination, worsened despite at least one 5-day course of IV methylprednisolone treatment (1 g/d) were enrolled. Patients received premedication with an antiemetic and IV MX 12 mg/m(2) every 12 weeks for up to 2 years, with a total cumulative dose not to exceed 96 mg/m(2). All patients were followed up for 1 year after treatment cessation. Efficacy was assessed at baseline, end of treatment, and 1-year follow-up using the Extended Disability Status Scale (EDSS) (which measures the functional disability level) (0 = normal findings on neurologic examination to 10 = death from MS complications). Tolerability was assessed before, during, and immediately after each infusion and at 2 weeks after each infusion, using direct questioning of, and spontaneous reporting by, the patients; physical examination; and laboratory assessments. Cardiac multigated acquisition scanning was performed at baseline and every 24 weeks during the treatment period. RESULTS: Forty-eight patients were enrolled (28 women, 20 men; mean [SD] age, 47.6 [8.6] years; mean [SD] disease duration, 12.5 [6.0] years; mean [SD] baseline EDSS score, 6.9 [1.2]). Twenty-three patients completed the entire course of treatment; the remaining 25 were withdrawn after 1 year of treatment due to lack of efficacy (22 patients), asymptomatic cardiac ejection fraction <40% (2), and severe septicemia and worsening of MS requiring extended respiratory support and hospitalization (1). Patients who completed only 1 year of treatment were younger compared with those who completed 2 years (mean age, 45.2 vs 50.1 years; P < 0.05). No significant change in mean EDSS score was found at the end of treatment or at 1-year posttreatment follow-up. In patients whose disability improved by 2-0.5 on the EDSS (11 patients at 1 year; 5 patients at 2 years), the degree of improvement noted at 1-year follow-up in patients with a baseline EDSS score 3.0 to 5.5 versus 6.0 to 7.5 and 8.0 to 9.0 was significant (both, P < 0.05). Severe adverse effects occurred in 14.6% of patients and included marked leukopenia (peripheral white blood cell count, <100 cells/µL) with urosepsis, requiring hospitalization in 7 patients, 1 of whom developed severe septicemia and worsening of MS, requiring >4 weeks of respiratory support. Cardiac ejection fraction decreased to <40% in 2 patients after 1 year of treatment (total dose, 48 mg/m(2)). These 2 patients were asymptomatic, but the investigators decided to discontinue treatment. Cardiac function returned to normal range (but not to near-baseline levels) within 12 weeks after treatment cessation. Although all patients were premedicated with antiemetics, 10 (20.8%) reported mild nausea (treated with repeat administration of antiemetics), and 2 of 16 (12.5%) premenopausal patients reported slightly increased bleeding during menstruation after l year of IV MX therapy, requiring no medical therapy or adjustment in the treatment protocol. CONCLUSIONS: Based on the results of this study in this small group of patients with worsening SPMS, IV MX treatment for up to 2 years was not associated with a significant change in EDSS score at the conclusion of treatment or 1 year after treatment cessation.

Tissue nitrogen-sparing effect of high protein diet in mice with or without ascites tumor treated with Acinetobacter glutaminase-asparaginase.

Forty-eight tumor-free mice and 32 mice bearing Ehrlich ascites tumor were randomized into 2 treatments, Acinetobacter glutaminase-asparaginase (AGA) (600 IU/kg/day for 7 days) and 0.9% NaCl controls, and into 2 or 3 isocaloric diets, normal protein (NP) (20 g protein/100 g diet), high protein (HP) (58 g protein/100 g diet), and zero protein (ZP) (tumor-free mice only). In tumor-free, NP-fed mice, AGA caused percentage reductions (P less than 0.01) in the nitrogen content of liver (50%), intestine (42%), thymus (89%), spleen (75%), and carcass (20%), but HP prevented this effect on intestine and carcass and caused percentage increases in the nitrogen content of liver (53%), intestine (36%), thymus (122%), and carcass (25%). In Ehrlich ascites tumor mice (NP or HP fed) AGA caused markedly lower (P less than 0.01) tumor burdens and increased nitrogen content of intestine (HP), kidney (NP and HP), and spleen (NP and HP). Ehrlich ascites tumor, AGA-treated, HP-fed mice ate 31% less food (P less than 0.01) (compared to NP) but HP resulted in percentage increases in the nitrogen content of liver (18%; P = 0.05), intestine (25%; P less than 0.05), and thymus (164%; P less than 0.01). In the Ehrlich ascites tumor, AGA group the HP diet caused higher hematocrit and serum total protein (both, P less than 0.05). Adverse nutritional effects of AGA seen in normal mice were markedly diminished in tumor-bearing animals. The observed nitrogen-sparing effects of the high protein: energy ratio may be relevant to humans and to other forms of neoplasia and chemotherapy.

Maternal characteristics influence response to DHA during pregnancy.

We explored the degree to which maternal and offspring outcomes resulting from consuming prenatal docosahexaenoic acid (DHA, 800mg/day) in a clinical trial were influenced by maternal characteristics. Among non-smokers, women who received DHA had heavier babies (adjusted mean difference (MD)=99g 95% CI 45-153, p<0.01; interaction p=0.01) and fewer low birth weight babies than control women (adjusted relative risk=0.43 95% CI 0.25-0.74, p<0.01; interaction p=0.01). From women who had not completed further education, children in the DHA group had higher cognitive scores at 18 months compared with control children (adjusted MD=3.15 95% CI 0.93-5.37, p=0.01; interaction p<0.01). Conversely, the children of women who completed further education in the DHA group had lower language scores than control children (adjusted MD -2.82 95% CI -4.90 to -0.73, p=0.01; interaction p=0.04). Our results support the notion that responsiveness to prenatal DHA may depend on the characteristics of specific population subgroups.

A potassium channel toxin from the secretion of the sea anemone Bunodosoma granulifera. Isolation, amino acid sequence and biological activity.

A peptide toxin affecting potassium channels was isolated from the sea anemone Bunodosoma granulifera. It facilitates acetylcholine release at avian neuromuscular junctions, competes with dendrotoxin I, a probe for voltage-dependent potassium channels, for binding to synaptosomal membranes of rat brain with a Ki of 0.7 nM and suppresses K+ currents in rat dorsal root ganglion neurones in culture. It represents a new structural type of potassium channel toxin with the sequence V1RCDWFKETA10CRHAKSLGNC20RTSQKYRANC30AKTLQCC37 (M(r) 4275, three disulfides).

Echocardiographic demonstration of decreased left ventricular dimensions and vigorous myocardial contraction during syncope induced by head-up tilt.

Two-dimensional echocardiography was performed during a head-up tilt test in 11 control subjects (group I) and 18 patients with recurrent unexplained syncope. In four patients (group II), the head-up tilt test was negative at baseline and after isoproterenol infusion. Syncope was induced during baseline head-up tilt in nine patients (group III) and after isoproterenol challenge in five (group IV). The echocardiographic variables assessed were left ventricular end-systolic and end-diastolic areas and percent fractional shortening. At the end of head-up tilt, end-systolic area decreased by 4.5 +/- 1.3 and 3.0 +/- 1.2 cm2 in groups III and IV, respectively, compared with 0.5 +/- 0.7 and 0.2 +/- 0.1 cm2 in groups I and II, respectively (p less than 0.04). Similarly, end-diastolic area decreased by 5.5 +/- 2.6 cm2 in group III compared with 2.7 +/- 1.9 and 1.75 +/- 0.4 cm2 in group I and II, respectively (p less than 0.04). Additionally, at the end of the baseline study, fractional shortening was significantly greater in group III and group IV (43 +/- 5%) than in groups I and II (p less than 0.01). In conclusion, syncope induced by head-up tilt is associated with vigorous myocardial contraction and a significant decrease in left ventricular end-systolic dimensions. This left ventricular hypercontractility may play an important role in the pathogenesis of syncope induced by head-up tilt.