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Intraprocedural rapid on-site evaluation (ROSE) of cytology specimens enhances cytopathology practice. More recently, ROSE diagnoses, like frozen section (FS) diagnoses, have guided immediate clinical decisions. In this study, we evaluated the diagnostic accuracy of our definitive ROSE diagnoses in our quality assurance system over a 52-month period.

The results from a detailed analysis of electromagnetic and current measurements during 39 lightning strikes to an airborne CV-580 aircraft are presented and discussed. It is concluded that 35 of the strikes were triggered by the presence of the aircraft in the vicinity of a highly charged region. The triggering mechanism appears to indicate that the negatively charged aircraft approached a positive charge center and encouraged the formation and propagation of leaders from the positive charge center and the aircraft. The remaining four events are shown to be cloud-to-ground strikes in which the aircraft was in the main channel in two cases and in a branch in two others. Representative examples of electromagnetic and current data are presented and discussed in detail to justify these conclusions.

This is a case study of deep, but narrow convective towers which split twice into right- and left-moving components in southwestern Oklahoma on 28 May 1985. Our analysis makes use of storm-intercept visual documentation, mobile soundings, surface mesonetwork data, and frequent soundings from special sites. The data show that the convective towers behaved in many respects like low-precipitation storms, having formed in an environment of large CAPE and moderately strong unidirectional shear. The observation of towers splitting even when there is no heavy precipitation at the surface implies that rain processes are not crucial to the splitting phenomenon. The tiny storms were confined to a region northeast of a surface cyclone and low-pressure area, near the intersection of the dryline and an old outflow boundary, where convective temperature was reached. Evidence is presented that the moist layer was deepened locally just prior to convective initiation, and that the deepening was related to low-level convergence associated with the westward motion of the dryline.

The application of genetic methods to the analysis of morphogenesis in maize is described. Several classes of floral mutants are differentiated through developmental studies and tests of epistasis. The results of mosaic and dosage analysis of Kn1, a dominant mutation affecting leaf development, are related to molecular studies of the gene.

Introduction BRAFV600 E mutations have been identified in a subset of patients with primary brain tumors. Combination therapy with BRAF and Mitogen-activated protein kinase (MEK) inhibitors (BRAF/MEKi) targeting sequential steps in the MAPK pathway has replaced BRAFi monotherapy as the standard of care in multiple tumors with BRAFV600 E mutations, and clinical evidence for this strategy continues to grow in primary brain tumors.Case series We describe four patients with BRAFV600 E mutated gliomas, including a 21-year-old woman with a ganglioglioma WHO grade I, a 19-year-old man with a pleomorphic xanthoastrocytoma WHO grade III, and 21-year-old and 33-year-old women with epithelioid GBM WHO grade IV, who achieved durable progression-free survival with combination BRAF/MEKi.Conclusion Combination of BRAF/MEK inhibition can be a novel, promising approach as targeted therapy in gliomas with BRAFV600 E mutations, especially those that are resistant to standard therapy. Our cases, along with other early reports utilizing dabrafenib/trametinib, highlight the importance of somatic next-generation sequencing, particularly in younger patients. Interim results from clinical trials utilizing dabrafenib/trametinib have been promising thus far, and our case series suggests that durable clinical benefit is possible, even in the setting of glioblastoma, WHO grade IV.

Methods to constrain peptides in a bioactive α‐helical conformation for inhibition of protein‐protein interactions represent an ongoing area of investigation in chemical biology. Recently, the first example of a reversible “stapling” methodology was described which exploits native cysteine or homocysteine residues spaced at the iand i+ 4 positions in a peptide sequence together with the thiol selective reactivity of dibromomaleimides (a previous study). This manuscript reports on the optimization of the maleimide based constraint, focusing on the kinetics of macrocyclization and the extent to which helicity is promoted with different thiol containing amino acids. The study identified an optimal stapling combination of X1= L‐Cys and X5= L‐hCys in the context of the model peptide Ac‐X1AAAX5‐NH2, which should prove useful in implementing the dibromomaleimide stapling strategy in peptidomimetic ligand discovery programmes.

As a 3D topological insulator, bismuth selenide (Bi2Se3) has potential applications for electrically and optically controllable magnetic and optoelectronic devices. Understanding the coupling with its topological phase requires studying the interactions of carriers with the lattice on time scales down to the subpicosecond regime. Here, we investigate the ultrafast carrier-induced lattice contractions and interlayer modulations in Bi2Se3thin films by time-resolved diffraction using an X-ray free-electron laser. The lattice contraction depends on the carrier concentration and is followed by an interlayer expansion accompanied by oscillations. Using density functional theory and the Lifshitz model, the initial contraction can be explained by van der Waals force modulation of the confined free carrier layers. Our theoretical calculations suggest that the band inversion, related to a topological phase transition, is modulated by the expansion of the interlayer distance. These results provide insights into the topological phase control by light-induced structural change on ultrafast time scales.

OBJECTIVE: To report the successful treatment of vancomycin-resistant Enterococcus(VRE) bacteremia using the combination of quinupristin/dalfopristin and high-dose ampicillin.CASE SUMMARY: A 38-year-old African American woman with relapsed acute myeloid leukemia and neutropenic fever developed VRE bacteremia following 3 successive courses of vancomycin for methicillin-resistant staphylococcal infections. Treatment with linezolid was initiated; however, after 9 days of therapy, blood cultures continued to reveal VRE and the patient became febrile. The patient was subsequently switched to quinupristin/dalfopristin and high-dose ampicillin. The fever resolved and all subsequent blood cultures were negative after the initiation of combination therapy.DISCUSSION: The emergence of VRE infections presents a treatment challenge in immunocompromised patients. When treating VRE infections in this patient population, the effectiveness of linezolid and quinupristin/dalfopristin is limited by their bacteriostatic activity when used as monotherapy. Recent in vitro data suggest synergistic activity with quinupristin/dalfopristin when used in combination with other antimicrobials in selected isolates of VRE.CONCLUSIONS: Persistent VRE bacteremia was successfully treated in this neutropenic patient using the combination of high-dose ampicillin and quinupristin/dalfopristin. Case reports and in vitro data suggest that concomitant therapy with high-dose ampicillin may be an effective treatment alternative for VRE infections not responding to standard therapy.

Background:Ibrutinib is a tyrosine kinase inhibitor commonly associated with atrial fibrillation, however additional cardiotoxicites have been identified including accelerated hypertension (HTN). The incidence and risk factors of new or worsening HTN after ibrutinib exposure is not as well known.Hypothesis:We hypothesize that ibrutinib use will lead to a significant increase from baseline blood pressure (BP).Methods:We conducted a retrospective chart review of 106 patients treated with ibrutinib to assess the incidence of HTN. Vital signs were reviewed at baseline, and at 1-, 3-, 6-, and 12-months after initiation of ibrutinib. HTN was defined as a BP >=130/90mmHg or current treatment with anti-hypertensive medications. Descriptive statistics for each group including mean BP are reported. Paired sample t-test was used to analyze longitudinal changes across groups. Chi-square analysis was used to determine factors significantly associated with the development of HTN. A p-value of less than 0.05 is considered statistically significant.Results:In the entire cohort, the prevalence of baseline HTN was 52.7% (n=56). Among patients without prior history of HTN, the average baseline BP was 119/71mmHg. After initiation of ibrutinib, 70% (n=35) demonstrated an increase in BP from baseline with 34% (n=18) developing criteria for new-onset hypertension. At the 1-, 3-, 6- and 12-month time points, the mean BP increased to 122/72, 125/74, 129/75; 132/74mmHg respectively. Among patients with a prior diagnosis of hypertension, the baseline BP was 125/73mmHg. After initiation of ibrutinib, 37% (n=21) had worsening of their BP, with a mean BP increase to 135/75, 136/74, 140/77, 145/76mmHg at 1-, 3-, 6- and 12-months respectively). Factors associated with interval increase in blood pressure include prior atrial fibrillation (p=0.015) and baseline HTN (p=0.063). Despite the newly developed HTN, 1/3 of patients did not receive adequate BP management.Conclusions:Ibrutinib is associated with development of hypertension and worsening of blood pressure. Cardiologists and oncologists must aware of this cardiotoxicity and aggressively manage BP elevations to reduce long term cardiovascular risk.

Several letters to the editor are presented in response to articles in previous issue including "Lost Art" by Sam Smith in the June 2015 issue, "Ring of Fire" and "DOT in the Dark" by Jason Cammisa in the July 2015.

No relevant conflicts of interest to declare.

Wood: Best Doctors: Consultancy; Inform Genomics: Consultancy.

Dose escalation of chemotherapy and radiation in conditioning regimens has been associated with lower relapse rates but not significantly improved overall survival in allogeneic transplants because of higher treatment related mortality. The advent of IV BU has allowed more precise dosing of this drug and permitted dose escalation to a greater degree than in the past. METHODS: Test dose (.8 mg/kg) IV BU was administered one week prior to start of the conditioning regimen and the desired AUC calculated from the Bu clearance. Starting at a standard AUC of 4800/24 hours, target dose levels were escalated in 20% increments to 5760, 6912, 7603 and 8663 uM-min/24 hours. BU was administered from day −7 to −3 by 90 hour continuous infusion accompanied by fludarabine, 30 mg/m2/d on days −7 to −3. All pts received tacrolimus and either alemtuzamab alone or ATG+/− low dose MTX for GVH prohylaxis. Standard antibiotic prophylaxis and supportive care was provided. RESULTS: 55 high risk pts, median age 39 (22–54), 20 MRD, 35 MUD, 26 AML, 7 ALL, 2 APL, 1 biphenotypic leukemia, 8 MDS, 5 NHL, 2 HD, 1 CLL, 1 CML, 1 CMML, 1 MF were enrolled on this IRB approved study. 30 patients received alemtuzamab, 19 ATG + MTX and 6 MTX only. Mean achieved AUCs were 4973(14 pts), 5638(7 pts), 7131(25 pts), 7053(7 pts), and 8680(2 pts) uM-min/24 hrs. The MTD was dose level 3 (target 6912, achieved 7131 uM-min). Grade 4 DLTs were grade 4 mucositis in 2/2 at level 5 and 1/7 at level 4 and 1/7 reversible VOD at level 4. One additional grade 5 toxicity was seen at dose level 1(liver failure), level 2 (mucositis) and level 3 (VOD). The incidence of grade 4 or 5 VOD was 2/55 or 4%. Median AUC for the entire group was 6312 uMol-min with the median in the group below the overall median being 5484 and the group above the median being 7394 uMol-min/24 hours; a 35% difference in dose between the lower and higher median values and a 54% increase over a standard AUC dose of 4800 uMol-min. When analyzed by AUC, pts above the median had a higher median overall survival (OS), 353 days vs 183 days (HR.48, p =.058) for those below the median and longer relapse-free survival (RFS), 818 vs 187 days (HR.47, p =.039). When divided by AUC in tertiles (median AUC values of 5106 (19 pts), 6431 (19 pts), and 7693 (17 pts) uMol-min/24 hrs respectively), the median OS in days for each group were 298, 353, and Not Reached and median RFS were 191, 353, and 818 days. Three group comparison using Cox model yielded p-values of.063 and.053 levels for RFS and OS, respectively. 2-year OS and RFS for the below and above median groups were.27 and.20 and.62 and.57, respectively. 2-year OS and RFS for the lowest, medium and highest AUC groups in the tertile analysis were.24 and.20.41 and.35, and.70 and.63, respectively. In multivariable analysis, higher AUC dose, use of ATG rather than alemtuzamab and having a MUD all demonstrated a trend toward improved outcomes with AUC being the strongest predictor. CONCLUSION: High AUC levels of busulfan can be safely achieved with targeted PK dosing and continuous IV infusion leading to improved overall survival and decreased relapse rates in patients undergoing allogeneic transplantation with either ATG or alemtuzamab as part of their GVHD prophylaxis.Shea: Otsuka Pharmaceuticals: Research Funding.

The article presents information on Earth phase in the body constitution as mentioned in Chinese medicine. As per the Chinese medicine, human body changes in accordance with the Earth element during late summer. It is observed that people with imbalances in the Earth phase in the body constitution may face achy muscles and dull headaches. As per the article, Earth corresponds with stomach and spleen of human body and affects emotional balances.

In this second part of the two‐part series, we discuss the formulation and implementation of groundwater processes into an existing climate model, by linking a groundwater reservoir and a rivers‐lakes reservoir with its land surface scheme. We present the parameterization and validation of these processes with river flow and soil moisture observations. We use the new scheme as a tool to investigate the role of the groundwater reservoir in controlling the spatial and temporal structure of large‐scale soil moisture fields. We find that where the water table is shallow, the groundwater reservoir is linked to the soil water reservoir through two‐way fluxes. At these locations, the role of the groundwater shifts from being primarily a sink to being primarily a source for the soil, as the season progresses from the wet spring to the dry autumn. Through the two‐way fluxes, groundwater exerts a certain degree of control on the root zone soil moisture fields; there is an apparent spatial correlation between the distribution of shallow water table and wet soil. Since the water table reflects long‐term climatic and topographic forcing and exhibits strong spatial organization, its link to the soil moisture gives the latter a certain degree of spatial organization as well. The slow changing nature of the water table acts to stabilize the temporal variations in soil water, giving the latter stronger seasonal persistence.

Soil moisture is a key participant in land‐atmosphere interactions and an important determinant of terrestrial climate. In regions where the water table is shallow, soil moisture is coupled to the water table. This paper is the first of a two‐part study to quantify this coupling and explore its implications in the context of climate modeling. We examine the observed water table depth in the lower 48 states of the United States in search of salient spatial and temporal features that are relevant to climate dynamics. As a means to interpolate and synthesize the scattered observations, we use a simple two‐dimensional groundwater flow model to construct an equilibrium water table as a result of long‐term climatic and geologic forcing. Model simulations suggest that the water table depth exhibits spatial organization at watershed, regional, and continental scales, which may have implications for the spatial organization of soil moisture at similar scales. The observations suggest that water table depth varies at diurnal, event, seasonal, and interannual scales, which may have implications for soil moisture memory at these scales.

Reports on the finalization of the merger of Lucent Technologies Inc. and Alcatel SA in April 2006. Amount of sales being targeted to be generated by a telecommunications equipment group that will be created by the merger; Percentage of shares in the combined operation that will be controlled by Alcatel; Reason behind the failure of the attempted merger of the companies in 2001.

Busulfan is an alkylating agent that is frequently used as the ablative component of allogeneic stem cell transplants in conjunction with immunosuppressive drugs such as cyclophosphamide or fludarabine. Busulfan has recently become available for IV use and has been shown to be effective and less toxic due to more reliable pharmacology than the oral form of this drug. While prolonged administration of this drug has not been feasible in the past, the parenteral formulation now makes this possible and permits re-evaluation of the efficacy, toxicity, and optimal dosing of this compound. Such an approach may reduce the dose-limiting hepatic, pulmonary and CNS toxicities that are seen with this compound. Here we report on 15 patients treated on a study using a continuous 90 hour infusion of this drug at 12.8 mg/kg adjusted body wt along with 30 mg/m2 fludarabine qd x 5 and alemtuzamab at doses of 0, 30, or 90 mg depending on the disease (myeloid or non-myeloid) and donor (MRD or MUD) followed by SCT. GHVD prophylaxis also included tacrolimus for all pts and short-course methotrexate for MRD patients who did not receive alemtuzamab. Subjects included 11 males and 4 females, median age 38, 6 MUD, 9 MRD, and 9 AML, 2 APL, 2 CML, 1 MDS and 1 ALL pt. All were high-risk based on being in 2nd remission or beyond (4), or having MDS or trilineage dysplasia(4), poor cytogenetics (3), refractory disease (2), prior transplant (1), or advanced CML (1). There have been no grade 3 or 4 toxicities due to drug infusion or during the initial period of aplasia. Neutrophil and platelet engraftment occurred on day + 14 and day + 16 respectively. There was one graft failure in a 54 yo man with MDS/AML who received a sex mismatched MUD transplant and subsequently underwent successful re-transplant on day 50. There have been two cases of grade II, one grade III and one grade IV aGVHD in 2 MRD and 2 MUD pts. Relapses have occurred in 5 pts after a median f/u of 10 months. Pharmacokinetics were obtained on 11 pts and compared the AUC obtained with a test dose given the day prior to initiation of the 90 hour infusion and the AUC of the continuous infusion. Test dose AUC predicted the full dose AUC with > 90% accuracy (range 3–19%, precision and bias of 9.5 and 1.4%). Mean daily AUC was 3539 umol min (range 1936 to 5591) with minimal variation between day 1 and 4 for the full-dose infusion. This is similar to the mean AUC observed in a control group of 8 pts treated with q 6 hr dosing and reflects the 3-fold inter-patient variability that has been reported when the parenteral drug is administered by intermittent infusion. 3 of the 4 pts with AUC data who have relapsed have had AUC concentrations below the mean. No AUC targeting was undertaken in this study but the predictive capacity of the test-dose strategy and the low AUC suggest that targeted dosing would be feasible and desirable with this approach. Studies with targeted dosing and prolonged infusion are currently underway to identify better the risks, toxicities and MTD of this approach.

For Abstract see ChemInform Abstract in Full Text.

Using a numerical model, the Regional Atmospheric Modeling System (RAMS), we simulate July precipitation over parts of the Mississippi River Basin and surroundings for each of three years, 1995–1997, with six different initial soil moisture patterns: three (control, dry, and wet) with a realistic (observationally based) spatial distribution, and three (control, dry, and wet) with a horizontally homogeneous distribution. Our goal is to determine the impact on future simulated precipitation of changing the initial soil moisture spatial distribution. The spatially homogeneous initial soil moisture pattern represents, in effect, a “wet west/dry east” anomaly imposed on the realistic soil moisture pattern (that reflects the west‐to‐east climatological gradient). The impact of this anomaly, i.e., increasing soil moisture in the western half and decreasing it in the eastern half of the simulation domain, is most pronounced for the dry experiments and weakens nonlinearly with increasing domain‐average initial soil moisture. In the dry regime, the impact is to enhance the total monthly precipitation in both the west and east. We examine the various terms in the atmospheric moisture budget to interpret these results. The changes in precipitation in the runs with a homogeneous compared to realistic initial soil moisture spatial pattern are consistent with enhanced evaporation in the western half of the model domain accompanied by enhanced west‐to‐east horizontal moisture transport that helps restore the initially depleted soil moisture in the east. In this manner, the zonal moisture flux acts toward re‐establishing the initial climatological soil moisture pattern of the region, thus acting as a negative feedback mechanism. In addition, the soil moisture anomaly generally produces diminished meridional moisture transport into the simulation domain from the south through a decrease in the low‐level meridional wind speed. This decrease in meridional flux acts in the same direction as the zonal flux change in the west, and in the opposite direction to the zonal flux change in the east. Since this change is most pronounced in the west, it therefore also contributes to the overall negative feedback of the atmospheric dynamics on the initial soil moisture. The persistence timescale of the impact of this particular soil moisture anomaly pattern on precipitation is on the order of 3 months in the dry regime. Sensitivity of the results to a change in convection scheme is also explored.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

To provide information on how cervicothoracic pain responds to osteopathic manipulative treatment, five subjects with acute or chronic pain received appropriate medication and three osteopathic manipulative treatments by the principal investigator using thrust and nonthrust techniques. The mean number of findings by both investigators on structural examination decreased considerably immediately after each of the three treatments. The number of findings increased in week 2 and decreased in week 3. The prinicpal investigator observed a further decrease by the final session, but the coinvestigator reported an increase. The pain scale score improved an average of nearly 3Wo. Thermography showed cooling of the cervicothoracic region in all subjects and conversion to a normal pattern in four. Osteopathic manipulative treatment should be considered for patients with acute or chronic cervicothoracic pain. The use of thermographic analysis in clinical osteopathic research seems warranted.