Incidence and determinants of migraine prophylactic medication in the Netherlands.
To estimate and examine the incidence and determinants of initiation of migraine-prophylactic therapy as well as the corresponding drug of choice over a period of 5 years following the use of specific abortive migraine drugs. By accessing data from a large prescription database, an identification of patients treated with ergotamine or a triptan from 1 January 1994 to 31 December 1998 was made. The cumulative incidence of initiation of migraine-prophylactic drugs (beta-blockers, serotonin antagonists, specific calcium antagonists, amitriptyline, clonidine and valproic acid) was estimated in patients following the use of ergotamine or a triptan. An assessment of the migraine-prophylactic drug of first choice was also performed. A few baseline determinants were analysed to highlight a possible association with the initiation of prophylactic therapy: age, gender, type of abortive migraine drug use and year of prophylaxis. Additional determinants included the analysis of drug-utilisation patterns, such as the consumption and switch patterns of abortive migraine drug use as well as co-medication use prior to prophylaxis. For this particular analysis a reference group (patients not having commenced prophylaxis) was selected from the initial study population. After having satisfied eligibility criteria, a total of 3999 first-time users of ergotamine and triptans were included of whom 479 (12%) had initiated migraine-prophylactic therapy. This corresponded to an incidence density of 6.0 per 100 person-years and was highest for patients younger than 45 years and for multiple abortive migraine drug users. The incidence fell considerably from 12.0 person-years in 1994 to 5.1 person-years in 1998. More than half of the patients had been prescribed a beta-blocker as the migraine-prophylactic drug of first choice by both general practitioners and neurologists. The use of antidepressants and/or benzodiazepines and oral contraceptives was significantly higher in patients starting prophylaxis compared with those who did not. The consumption of abortive migraine drug use (4.0 defined daily doses per month vs 3.7 defined daily doses per month), and switch patterns (27.1% vs 30.9%) were similar for patients starting and not starting prophylaxis. The overall incidence of initiation of migraine-prophylactic therapy following the use of abortive migraine analgesics was 6.0% per year and fell considerably during 5 years of the study. Beta-blockers were the migraine-prophylactic drugs of first choice for general practitioners and neurologists. In our study we could not determine any factors clearly associated with the initiation of migraine prophylaxis besides prior use of antidepressants and benzodiazepines. A future assessment of the usage patterns of migraine-prophylactic drugs may provide detailed information concerning the effectiveness and tolerability.


The first fifty - a review of the South African Medical Congresses.
This historical résumé, a collation of facts from various sources which lie scattered among the pages of early medical journals of our land, has been composed in an attempt to give some continuity of substance to this particular part of South African medical history which will be celebrated by our Jubilee Congress in Johannesburg this year.


A randomized controlled trial of recovery management checkups for primary care patients: Twelve-month results.
Primary care settings like federally qualified health centers (FQHC) are optimal locations to identify individuals with substance use disorders (SUD) and link them to SUD treatment, yet successful linkage has proven difficult. Recovery management checkups for primary care (RMC-PC) is a promising method for increasing linkage to care, engagement in treatment, and reducing substance use. Participants (n = 266) who received screening, brief intervention, and referral to treatment (SBIRT) at four FQHC sites and needed SUD treatment were randomized to receive SBIRT only or SBIRT+RMC-PC. All participants received SBIRT prior to randomization as part of usual care while those in the experimental group also received quarterly checkups. All participants completed research interviews at enrollment and 3, 6, 9, and 12 months post-enrollment. The primary outcome was whether participants received any days of SUD treatment. Key secondary outcomes were days of SUD treatment (total and by SUD level of care), days of alcohol or drug abstinence, and a reduction in days of specific substance use, all based on self-report. Relative to participants receiving SBIRT only, participants assigned to SBIRT+RMC-PC were significantly more likely to have received any SUD treatment over 12 months (adjusted odds ratio [AOR] = 3.85) and more days of SUD treatment over 12 months (Cohen's effect size d = +0.41). The SBIRT+RMC-PC group also reported significantly more days of abstinence over 12 months (d = +0.30), fewer days of alcohol use (d = -0.20) and cannabis use (d = -0.20), and lower combined substance use frequency (d = -0.25). Days of treatment were found to positively mediate the direct effect of SBIRT+RMC-PC on days of abstinence. This study provides further evidence of the effectiveness of the "referral to treatment" component of SBIRT when combined with RMC for patients in primary care settings, including those with drug use problems. Moreover, results demonstrate the value of repeated checkups on longer-term treatment and substance use outcomes.


[Development of an Instrument to Assess the Nursing Professional Pride].
The purpose of this study was to develop an instrument to assess nursing professional pride. Fifty-six preliminary items were identified through literature review and focus group interview of nurses working in a hospital. Of these, 45 preliminary instruments were completed over 0.80 of content validity index. To verify the reliability and validity of the preliminary instrument, data were collected from 294 nurses. The data were analyzed using factor analysis and multidimensional scaling analysis. From the factor analysis, 27 significant items were divided into 5 subscales. These subscales were as follows: feeling of vocation, role satisfaction, role of problem solver, self-achievement, and willingness to stay. The nursing professional pride also established criterion-related validity, discriminant validity, and group validity. Cronbach's a of the instrument was .92, and the subscales ranged from .74 to .85. The developed scale for nursing professional pride shows validity and reliability. The significance of this study is the development of an instrument capable of measuring nursing professional pride. To verify the relevance of this instrument, conducting comparative studies is suggested.


A plasma factor participates in the cryoactivation of plasma inactive renin.
Plasma inactive renin (IR) can be cold activated (-4 degrees C). This process is called cryoactivation. The mechanism of cryoactivation is not yet elucidated. To investigate the mechanism of cryoactivation, we initially determine the isoelectric point (pI) of plasma active renin (AR) and IR by means of isoelectric focusing. The electrofocusing was performed in a LKB 8100-1 column containing a sucrose gradient and pH 3.5-10 ampholine under 4 degrees C. We found that the pI of AR was 5.0 and 3.9 whereas the pI of IR was 5.6. By using pH 4-6 ampholine, we separated IR from AR and added all fractions containing only IR to each of the electrofocusing column eluates (pH 4-6 ampholine). We found there was no increase in renin activity. If each fraction of electrofocusing eluate (after pH 4-6 ampholine) was cryoactivated, without adding the IR containing fractions, a small increase in angiotensin I (AI) generation was seen in the fractions of pH 4.9-5.1. However, when eluates from the electrofocusing column using pH 3.5-10 ampholine were added to fractions containing only inactive renin, and cryoactivation was subsequently performed, a peak increase in AI generation was found in the fractions corresponding to pH 4.9-5.1. Therefore, cryoactivation may expose certain enzyme(s) which have the pI of 4.9-5.1 and can activate inactive renin. We further found that these fractions could split the synthetic substrate S-2302. Such an activity may be produced by plasmin or related enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)


From untargeted LC-QTOF analysis to characterisation of opines in abalone adductor muscle: Theory meets practice.
Abalone have a unique ability to use pyruvate, various amino acids and dehydrogenases, to produce opines as means to prevent the accumulation of NADH during anaerobic conditions. In this study, the theoretical masses, formulae and fragment patterns of butylated opines were used to predict which of these compounds could be found in the abalone adductor muscle using untargeted liquid chromatography quadrupole time-of flight-mass spectrometry. These findings were validated using synthesised opine standards. In essence alanopine, lysopine, strombine and tauropine produced in abalone adductor muscle could be characterised using the highest identification confidence levels.


An information model for medical events.
Information gathered during the healthcare process is lost when forced into rigidly structured record-oriented databases. By contrast, content can be difficult to manipulate if stored as unstructured text. Spurred by the requirements of electronic publishing, military procurement and the Internet, new robust standards for structuring documents have been developed and deployed. These standards can provide a foundation for a document-based Electronic Medical Record System. In order to fully exploit this added flexibility, an information model is necessary to define both the direct and contextual content of documents. Once context, as well as fact, are recorded in formal structures, inferential techniques can either selectively extract knowledge and data from documents or aggregate data to create summaries so that all interested and authorized parties have a better chance of meeting their information needs from a single, permanent data source.


Quantitative, precise and multi-wavelength evaluation of the light-to-heat conversion efficiency for nanoparticular photothermal agents with calibrated photoacoustic spectroscopy.
Biomedical photothermal therapy with optical nanoparticles is based on the conversion of optical energy into heat through three steps: optical absorption, thermal conversion of the absorbed energy and heat transfer to the surrounding medium. The light-to-heat conversion efficiency (LHCE) has become one of the main metrics to quantitatively characterize the last two steps and evaluate the merit of nanoparticules for photothermal therapy. The estimation of the LHCE is mostly performed by monitoring the temperature evolution of a solution under laser irradiation. However, this estimation strongly depends on the experimental set-up and the heat balance model used. We demonstrate here, theoretically and experimentally, that the LHCE at multiple wavelengths can be efficiently and directly determined, without the use of models, by calibrated photoacoustic spectroscopy. The method was validated using already characterized colloidal suspensions of silver sulfide nanoparticles and maghemite nanoflowers and an uncertainty of 3 to 7% was estimated for the LHCE determination. Photoacoustic spectroscopy provides a new, precise and robust method of analysis of the photothermal capabilities of aqueous solutions of nanoagents.


Treatment of disseminated intravascular coagulation.
The treatment of DIC is extremely complex, stemming from the fact that it complicates many different disorders and may have a variety of clinical manifestations. In addition, there continues to be a lack of well-controlled studies regarding various methods of management in relatively homogeneous groups of patients. Therefore treatment continues to be controversial and probably will remain so in the near future. However, it is clear that any careful clinical and laboratory observations in groups of patients with the same underlying disorder are extremely helpful in elucidating the natural history of the process, in determining its effect on the patient, and clarifying whether certain therapeutic interventions may be helpful. Therefore the continued accumulation of careful clinical studies will help in determining the proper management of DIC in patients with the same underlying disorder and in given individual situations.


A retrospective study on the prognostic value of preoperative C-reactive protein to albumin ratio in patients with oral cavity squamous cell carcinoma.
Although the C-reactive protein-to-albumin ratio (CAR) can predict poor outcomes in assorted cancers, its prognostic value in oral cavity squamous cell carcinoma (OSCC) remains unclear. We explored the value of preoperative CAR in predicting clinical outcomes in OSCC patients treated with radical surgery. All the recommended cutoff values were defined analyzing receiver operating characteristic curves or overall survival (OS). Dichotomization was performed on the basis of optimal CAR cutoff, and we compared the clinicopathological features between groups. Kaplan-Meier analysis was also performed to compare OS curves between the two groups. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to find the clinical characteristics that were most closely correlated with disease free survival (DFS) and overall survival (OS). A nomogram incorporated CAR and several clinicopathological factors was established to predict prognosis and its accuracy was evaluated using concordance index (c-index). In this retrospective study, a total of 326 patients with newly diagnosis of OSCC and received primary surgery between 2008 and 2017 were enrolled. Through the executed ROC curve analyses, the optimal CAR cutoff derived was 0.195 (area under the curve = 0.718, p < 0.001), with this cutoff exhibiting a discrimination ability superior to that of other inflammation-based prognostic scores after comparing the area under curves. Multivariate analysis demonstrated that CAR (≥0.195/<0.195) was associated with OS (hazard ratio 3.614; 95% CI [1.629-8.018]; p = 0.002) and DFS (hazard ratio 1.917; 95% CI [1.051-3.863]; p = 0.029). Kaplan-Meier analysis and log rank test revealed a significant difference in DFS and OS curves between patients with low CAR (<0.195) and those with high CAR (≥0.195; both p < 0.001). The c-index of the nomogram based on TNM system alone was 0.684 and could be increased to 0.801 if CAR and other clinicopathological factors were included. Preoperative CAR could constitute an independent prognostic indicator for OS and DFS prediction in OSCC patients treated with curative surgery. The established nomogram that incorporated CAR and prognostic factors might increase the accuracy of prognostic prediction for patients with OSCC.


Gold-Triggered Uncaging Chemistry in Living Systems.
Recent advances in bioorthogonal catalysis are increasing the capacity of researchers to manipulate the fate of molecules in complex biological systems. A bioorthogonal uncaging strategy is presented, which is triggered by heterogeneous gold catalysis and facilitates the activation of a structurally diverse range of therapeutics in cancer cell culture. Furthermore, this solid-supported catalytic system enabled locally controlled release of a fluorescent dye into the brain of a zebrafish for the first time, offering a novel way to modulate the activity of bioorthogonal reagents in the most fragile and complex organs.


Intratumor variability in prognostic indicators may be the cause of conflicting estimates of patient survival and response to therapy.
The DNA index, percentage of S-phase cells, proliferation fraction, and glutathione (GSH) content were determined at more than 1100 separate sites in 140 human tumors and 140 normal tissues. The study showed that the variability was so great from site to site within a tumor that there was only a 61% chance of identifying an aneuploid tumor clone (when present) if only a single site sample was analyzed for DNA content. Similar broad variability was observed in the percentage of S-phase cells, proliferation fraction, and glutathione content. Since these tumor characteristics are often used to predict the outcome of therapy and patient survival, the inaccuracy and underestimation of the test results may cause conflicting or erroneous predictions. The probability of finding an aneuploid clone or elevated percentage of S-phase cells proliferation fraction and GSH content increased dramatically as the number of sample sites studied per tumor was increased. Statistical analyses indicated that in order to achieve a 90% probability that the test results for these parameters were representative of the whole tumor: (a) all single site testing should be abandoned; (b) assays should be performed on samples taken from 3-7 different sites within each tumor; or (c) samples from each tumor should be pooled and the analyses run on a thoroughly mixed or homogenized aliquot of the multisite sample.


The best features of diamond nanothread for nanofibre applications.
Carbon fibres have attracted interest from both the scientific and engineering communities due to their outstanding physical properties. Here we report that recently synthesized ultrathin diamond nanothread not only possesses excellent torsional deformation capability, but also excellent interfacial load-transfer efficiency. Compared with (10,10) carbon nanotube bundles, the flattening of nanotubes is not observed in diamond nanothread bundles, which leads to a high-torsional elastic limit that is almost three times higher. Pull-out tests reveal that the diamond nanothread bundle has an interface transfer load of more than twice that of the carbon nanotube bundle, corresponding to an order of magnitude higher in terms of the interfacial shear strength. Such high load-transfer efficiency is attributed to the strong mechanical interlocking effect at the interface. These intriguing features suggest that diamond nanothread could be an excellent candidate for constructing next-generation carbon fibres.


Elevated Cardiovascular Risks among Postmenopausal Women: A Community Based Case Control Study from Nepal.
Cardiovascular disease (CVD) is one of the leading causes of death worldwide which is more prevalent in women after menopause. Hormonal changes associated with menopause are accountable for dyslipidemic pattern that causes CVD and associated complications. Therefore, the present study was commenced to compare the lipid profile in pre- and postmenopausal women. A descriptive cross-sectional study was conducted at Manmohan Memorial Institute of Health Sciences (MMIHS) from February 2016 to July 2016. A total of 260 fasting samples were collected from healthy women, 130 from premenopausal and 130 from postmenopausal women, and analyzed for Total Cholesterol (TC), Triacylglycerol (TAG), High Density Lipoprotein Cholesterol (HDL-C), and Low Density Lipoprotein Cholesterol (LDL-C) as per the guideline provided by the reagent manufacturer (Human, Germany). All the parameters were analyzed by Stat Fax 3300 semi auto analyzer. TC, TAG, HDL-C, and LDL-C were highly significantly increased in postmenopausal women when compared to premenopausal women. LDL/HDL ratio was significantly elevated in postmenopausal women than in premenopausal women. BMI was significantly positively correlated with TC and TAG in both pre- and postmenopausal population and it was positively correlated with HDL-C in premenopausal population while negatively correlated in postmenopausal population. Since more of the atherogenic lipid parameters are increased in postmenopausal women, they appear to be more prone to have CVD and associated complications in near future. Hence, it is mandatory to monitor and manage dyslipidemic pattern in every woman experiencing menopause.


Palms do not undergo secondary stem lengthening: a response to Renninger and Phillips (American Journal of Botany 99: 607-613).
Woody stems that have completed some maturation of metaxylem elements should not be capable of further axial extension ("secondary stem lengthening"). However, this mechanism has been claimed by Renninger and Phillips (American Journal of Botany 99: 607-613) to be a feature of the palm Iriartea deltoidea. In response, we describe structural features of palm stems based on extensive known features of their anatomy and development. In addition to the inability of metaxylem vessels to extend after they are mature, fully differentiated fibers of the vascular bundle sheath, which would exist at the time of proposed stem elongation would not be capable of belated extension. "Vessel spirals" claimed by these authors to be capable of stretching to accommodate secondary stem lengthening does not refer to well-established features of the course of vascular bundles. The approach adopted by Renninger and Phillips simply measures stems of different sizes as an implied developmental series. Consequently, results do not take into account changes in the development of the palm stem as it ages. The existence of secondary stem lengthening in the palm Iriartea deltoidea, something never before observed in any tree, cannot occur because it would indeed disrupt mature metaxylem vessels and would also require the secondary extension of mature lignified fibers.


Chest pain and hypertension in an 18 year old girl.
We describe the case of an 18 year old lady who presented with chest pain, breathlessness and hypertension. The initial diagnosis of renal artery stenosis, while correct, was incomplete. The finding of a reduced right radial pulse suggested the possibility of a large vessel vasculitis. She was also found to have critical coronary artery disease that required stenting and aortic incompetence. Renal artery stenting was also performed. Additional investigations confirmed Takayasu's arteritis. With immunosuppressive therapy and stenting she is now well and normotensive but may require aortic valve replacement in the future.


Delayed esophageal anastomotic complication and ramucirumab therapy: A case report.
Current NCCN guidelines for second-line therapy in recurrent or metastatic esophago-gastric cancers recommend the use of VEGF inhibitors such as ramucirumab. VEGF inhibitors have been shown to be associated with gastrointestinal perforation in clinical trials and late colorectal anastomotic leaks in a few case reports. Here, we present a case of late esophageal anastomotic leak in a patient receiving ramucirumab. Case information was obtained from our institution's electronic medical records. The patient was found to have T4N1M0, poorly differentiated invasive adenocarcinoma and subsequently received neoadjuvant chemoradiation followed by hybrid Ivor-Lewis esophagectomy 6 weeks later. He recovered well with no leak or perioperative complications. The patient had disease progression 9 months postoperatively on CT and PET imaging. Sixteen months after surgery he began paclitaxel and ramucirumab and 16 weeks after ramucirumab initiation, he was found to have an esophago-pulmonary fistula in the region of the anastomosis. Biopsies were negative for recurrence at the anastomosis. He died one week later from progressive pneumonia despite stenting. In conclusion, this is the only known report of delayed esophageal anastomotic complication associated with ramucirumab. VEGF inhibitor therapies such as bevacizumab have been associated with late (greater than 3 months postoperative) colorectal anastomotic complications including fistulas and leaks. Risk factors that have been associated are perioperative radiotherapy and history of early postoperative leak. These findings raise concern whether VEGF inhibitor therapy should be used in post-esophagectomy patients with recurrence if these rare but catastrophic events are likely to be terminal.


Increased serum concentration of IgA2 subclass and IgA2/IgA1 ratio: specific markers of chronic alcoholic abuse?
Enhanced serum IgA concentrations are common in alcoholic liver cirrhosis, but functional differences between IgA subclasses and their relation with interleukin-6 (IL-6) have not been described. Distinct immunoregulatory mechanisms may exist that selectively affect one subclass. This possibility prompted us to investigate the distribution of IgA1 and IgA2 subclasses in the serum of 25 heavy alcohol drinkers (alcohol: 80 to 200 g per day) without clinical disorders, in comparison with 35 patients affected by alcoholic liver cirrhosis, 29 viral hepatitis patients and 33 social drinkers as a control group. Mean (+/- SD) IgA2 concentration (0.56 +/- 0.31 g/l) was significantly increased (p < 0.01) in heavy alcohol drinkers, with an IgA2/IgA1 ratio of 0.33 +/- 0.12, while the mean total IgA concentration was similar to the control group. Mean IgA1 and IgA2 concentrations were significantly increased (p < 0.001) in alcoholic liver cirrhosis patients (6.13 +/- 4.52 g/l and 1.83 +/- 1.93 g/l respectively, with an IgA2/IgA1 ratio of 0.32 +/- 0.19) and viral hepatitis patients (3.66 +/- 2.59 g/l and 0.69 +/- 0.67 g/l respectively, with an IgA2/IgA1 ratio of 0.21 +/- 0.14) High serum IL-6 concentrations (34 +/- 33 ng/l) were correlated with elevated IgA1 and IgA2 concentrations only in patients with alcoholic liver cirrhosis. IgA2 subclass and IgA2/IgA1 ratio could therefore be used as markers of chronic alcohol abuse directly related to the extent and duration of the alcohol abuse and the effectiveness of alcohol withdrawal.


Structural, energetic and dynamical properties of sodiated oligoglycines: relevance of a polarizable force field.
Oligoglycine peptides (from two to ten residues) complexed to the sodium ion were studied by quantum chemical and molecular mechanics calculations to understand their structural and energetic properties. Modeling such systems required the use of a polarizable force field and AMOEBA, as developed by Ren and Ponder [J. Comput. Chem., 2002, 23, 1497], was chosen. Some electrostatic and torsional parameters were re-optimized using a rigorous procedure and validated against both geometric and energetic ab initio data in the gas phase. Molecular dynamics simulations were performed on seven sodiated octa-glycine (G(8)) structures. Structural transitions were generally observed (with the notable exception of the a-helix), leading to new structures that were further proved by ab initio calculations to be of low energies. The main result is that for G(8)-Na(+), there is a compromise between sodium peptide interactions and multiple hydrogen bonding. The accuracy achieved with AMOEBA demonstrates the potential of this force field for the realistic modeling of gaseous peptides.


Prevalence of Eye and Vision Disorders in the Military Health System, Fiscal Year 2018.
Eye and vision disorders are estimated to impact 7.08 million people in the United States, including 1.62 million under the age of 40. This study uses the Vision and Eye Health Surveillance System (VEHSS) case definitions to assess the burden of eye and vision disorders in a universally insured, nationally representative population. This retrospective, cross-sectional study applied the VEHSS case definitions to TRICARE claims data collected from the Military Health System Data Repository and Defense Enrollment Eligibility Reporting System during 2018. Beneficiaries aged 0-64 years during the fiscal year 2018 were identified with inpatient and outpatient codes matching to the VEHSS diagnostic case definitions, which were organized into 17 categories of eye and vision disorders classified by the ICD-10. Beneficiaries were recorded only once per category but allowed to match to multiple categories. Analyses included descriptive statistics of patient demographics and prevalence of eye disorders. We identified 4,548,897 TRICARE Prime/Plus beneficiaries (54.86% men and 45.14% women), of whom 22.93% were diagnosed with at least one disorder in 2018. Of those with a diagnosis, the majority were men (50.13%), adults (74.91%), and of or sponsored by a senior enlisted rank (57.83%), used as socioeconomic proxy. Disorders of refraction and accommodation were most prevalent, followed by infectious and inflammatory diseases. Potentially preventable and treatable conditions, including amblyopia and strabismus, infectious and inflammatory disease, and diabetic complications, affected up to 22% of those with vision disorders. This study represents the first use of VEHSS measures in a universally insured, socioeconomically diverse population. Identification of potentially treatable or preventable conditions indicates significant opportunity to mitigate the burden of eye and vision disorders in the Military Health System.


Application of external lubrication during the roller compaction of adhesive pharmaceutical formulations.
A novel use of external lubrication has been investigated in which magnesium stearate was applied directly to the roll surface during roller compaction. A scalable parameter; travelling roll distance per shot (D(pS)), has been defined which ensures that an equal amount of magnesium stearate is applied to the roll surface per rotation at any roll speed. It was found that a formulation containing 20% w/w of either the API Pravastatin or Ibipinabant required a smaller D(pS) than a placebo formulation in order to prevent roll adherence. The inherent adhesiveness, and hence the required amount of external magnesium stearate to prevent roll adhesion, will depend on the material properties of the formulation. The amount of magnesium stearate transferred from the roll surface to the ribbon was measured using inductively coupled plasma optical emission spectroscopy and was found to be less than 0.01% w/w. This is a significant reduction in magnesium stearate compared to the normal manufacturing procedure of blending 0.25-2.0% w/w within the formulation.The advantage of external lubrication during roller compaction is the significant reduction in magnesium stearate from the formulation which could lead to the production of tablets with superior mechanical properties and faster dissolution times.


Endothelin-1 messenger [corrected] ribonucleic acid expression in pulmonary hypertensive and nonhypertensive chickens.
Four hundred 1-d-old Cobb broilers were distributed in 3 groups: group A comprised broilers maintained under natural hypobaric hypoxia (Bogotá, Colombia); group B comprised broilers under relative normoxia (Villavicencio, Colombia); and group C comprised broilers maintained at 460 m above sea level (Villavicencio, Colombia) from d 1 to 25 of age, and then moved to 2,638 m above sea level (Bogotá, Colombia). Broilers were designated as nonpulmonary hypertensive (NPHB) and pulmonary hypertensive (PHB), to estimate possible differences between them in the lung expression of endothelin 1 (ET-1) mRNA at 24 and 42 d of age. In group A, 12 NPHB and 12 PHB were used for determination of ET-1 mRNA expression at 42 d. In group B, nonPHB were found, and therefore, ET-1 mRNA expression was detected in 48 NPHB, 24 of them in each age group (24 and 42 d). In group C, only NPHB were encountered at 42 and 53 d, and ET-1 mRNA expression was determined at 42 d in 24 birds. The ET-1 mRNA levels of PHB of group A at 42 d were significantly higher than the correspondent ones in NPHB of groups A (P < 0.001) and C (P < 0.05) at the same age. No differences in ET-1 mRNA expression were encountered between NPHB of groups A and B at 42 d (P > 0.05). However, ET-1 mRNA expression was higher in group C than the correspondent one in NPHB of groups A and B at 42 d (P < 0.001). The present data suggest that ET-1 may play a major role in pulmonary hypertension pathophysiology. It is possible that chickens should be exposed to hypobaric hypoxia before d 24, as a requisite to develop pulmonary hypertension. These results might provide clues for future studies in pulmonary vasoconstriction and vascular remodeling.


Chromatographic determination of hydrophobicity of dialkylimidazolium ionic liquids using selected stationary phase.
The determination of hydrophobicity of ionic liquids (ILs) is essential for the reason that some of these salts' classes are of toxic character. The conventional shake flask method of logP estimation fails in case of ILs. This is connected with their ionic character. Therefore other methods need to be developed and optimized. Chromatographic methods seem to be the proper ones. For that reason, several specific stationary phases (octadecyl, octyl, aminopropyl, alkylamide, cholesterolic, immobilized artificial membrane, phenyl) have been used for the determination of logk(w) of alkylimidazolium ILs. Then, logk(w) were used for the correlation with calculated logP for ILs. Depending on applied calculation procedure, high values of determination coefficient were obtained for alkyl-based silica stationary phases or for more specific column packing. This result is very promising as it has already been proven that several, different in nature, stationary phases can be successfully used for estimation of logP of IL cations.


Language and power: ascribing legitimacy to interpretive research.
More than merely describing what constitutes a good or truthful interpretation, all judgments about the legitimacy of knowledge claims can be understood as enacting relations of power. That is, our understanding of what it means to make a reasonable claim to knowledge is already caught up in relations of power that privilege some perspectives and marginalize others. Language, understood as productive rather than reflective of meaning, both enables and constrains the kinds of statements we are entitled to make. Competing discourses do not exist equally in the world but rather differ in terms of what they are held to explain and what effect they have. The authors explore these issues and suggest that evaluating interpretive research involves not only epistemological issues but also questions of value and power.


Interaction effects in conductivity of Si inversion layers at intermediate temperatures.
We compare the temperature dependence of resistivity rho(T) of Si-metal-oxide-semiconductor field-effect transistors with the recent theory by Zala et al. In this comparison, the effective mass m* and g* factor for mobile electrons have been determined from independent measurements. An anomalous increase of rho with temperature, which has been considered as a signature of the "metallic" state, can be described quantitatively by the interaction effects in the ballistic regime. The in-plane magnetoresistance rho(B(axially)) is only qualitatively consistent with the theory; the lack of quantitative agreement indicates that the magnetoresistance is more sensitive to sample-specific effects than rho(T).


Recent advances in genetic research on schizophrenia.
Evidence for genetic factors in schizophrenia is reviewed with regard to family, twin and adoption studies, and recent advances in molecular genetic technology are applied to explore possible gene loci susceptible to schizophrenia. Application of neuropsychological and neuroimaging methodologies are also reviewed with an aim to develop criteria for defining phenotypes for genetic studies.


[Clinical Research Using the Large Health Insurance Claims Database].
The JMDC Claims Database® contains completely anonymized receipt information on the insured members of health insurance associations. The number of registered users is approximately 9.6 million (6% of the population) as of May 2020. In this database, it is possible to track even outpatient treatment, even if the patient changes the medical facility, as long as the insurer of the subscriber's health insurance does not change, so that long-term medical treatment could be targeted as a research theme. However, as the data do not contain medical record information, it is not possible to obtain laboratory values, although it is possible to know whether clinical tests have been performed. For pharmaceutics-related research, the most suitable use of the receipt database like JMDC Claims Database® seems to be the investigation of actual prescriptions. However, the research topics that pharmacists are interested in are probably comparisons of drug effects, drug-drug interactions, or causal analysis of drugs and side effects. However, laboratory data for evaluating drug efficacy is not available in the receipt database, and the accuracy of the disease name in the database becomes problematic when using the disease name as information indicating the occurrence of side effects. In this review, we introduce our studies performed by using JMDC Claims Database® and how to manage the above-described problems. We hope that this study will be helpful to those who are going to engage in research using medical big data.


Differences in interpretation of haemoglobin A1c values among diabetes care professionals.
To assess the expected precision of HbA1c measurements and the magnitude of HbA1c changes eliciting the advice to change treatment among diabetes care professionals. A seven-item questionnaire was sent to participants through a website. The survey focused on physicians and nurses involved in diabetes care. In total, 104 physicians, 177 diabetes specialist nurses, and 248 primary care nurses responded to the survey. A large number of the nurses (44%) and only a small number of the physicians (4%) were not aware of the inherent uncertainty of HbA1c results. Nurses considered adjusting therapy based on very small changes in HbA1c whereas physicians in general adhere to 0.5% (5.5 mmol÷mol) as a clinically meaningful cut-off point. After therapy adjustment, a very small (0.1%) or no increase in HbA1c was considered to be significant enough to conclude that glucose regulation has worsened by 49% of the nurses and only 13% of the physicians. Significant differences exist in the interpretation of changes in HbA1c results between physicians and nurses. Nurses consider therapy changes based on very small changes in HbA1c, whereas physicians preferably agree to the clinically relevant change of 0.5% (5.5 mmol÷mol). Changing therapy based on relatively small changes in HbA1c might lead to undue adjustments in the treatment of patients with diabetes. There is a clear need for more training for all diabetes care professionals about both the clinical significance and accuracy of HbA1c measurements.


Acute dislocation of the patella with osteochondral fracture: a review of eighteen cases.
Eighteen patients with acute dislocation of the patella had associated osteochondral fractures. This fracture complicates approximately 5% of all acute dislocations of the patella occurring in children. Three types of fracture patterns were noted. All patients who were treated by immediate arthrotomy and excision or replacement of the osteochondral fragment and repair of the acute dislocation of the patella made an uneventful recovery with no recurrence of the dislocation. In those patients in whom the osteochondral fragment was removed but with no repair the dislocation recurred.


Caput mortuum: spectroscopic and structural studies of an ancient pigment.
The use of a pigment variously described as caput mortuum, usta or ostrum to provide a deep purple colour in ancient wall-paintings was highly prized, despite the technical difficulties associated with its application. With the Raman spectroscopic characterization of pigments in ancient frescoes and wall-paintings becoming more widespread, it is timely to consider the identification of this material either as a generic haematite alone or in admixture with contemporary blue pigments. Here, Raman and infrared spectroscopic, X-ray diffractometric and scanning electron microscopic structural studies have been undertaken to characterize caput mortuum and to identify a specimen of Roman wall-painting dating from the 3rd century.


Risk factors for mortality from sepsis in an intensive care unit in Ecuador: A prospective study.
To investigate risk factors for mortality from sepsis in an intensive care unit (ICU) in Quito-Ecuador and their association to adherence to Surviving Sepsis Campaign recommendations.Prospective cohort study of patients with severe sepsis/septic shock admitted to the ICU of a public Ecuadorian hospital from March, 2018 to March, 2019. Demographic, clinical, treatment, and outcome data were collected from patients' health records. Patients were divided into 2 groups according to ICU survival or death. Log-binomial regression models were used to identify risk factors for mortality.In total, 154 patients were included. Patients who died in the ICU (n = 42; 27.3%) had higher sequential organ failure assessment score (median 11.5 vs 9; P<.01), more organ dysfunction (median 4 vs 3; P<.0001), and received greater volumes of fluid resuscitation in the first 6 hours (median 800 vs 600 mL; P = .01). Dysfunction of > 2 organs was a risk factor for mortality (relative risks [RR] 3.80, 95% CI 1.33-10.86), while successful early resuscitation (RR 0.32, 95% CI 0.15-0.70), successful empirical antibiotic treatment (RR 0.38, 95%CI 0.18-0.82), and antibiotic de-escalation (RR 0.28, 95%CI 0.13-0.61) were protective factors.Dysfunction of >2 organs was a risk factor for mortality from sepsis while successful early resuscitation and appropriate antibiotic treatment were protective.


[Research into sensitization and allergies to latex: results after 10 years of the use of powder-free latex gloves].
To compare the prevalence of sensitization and allergy to natural rubber latex amongst Erasmus Medical Centre (MC) operating theatre employees before and 10 years after the introduction of powder-free latex gloves. Descriptive study. Employees working permanently in the operating theatre were evaluated in 1998 (n = 163) and in 2009 (n = 178) for sensitization and allergies to natural latex by means of questionnaires, serological analyses and skin testing. The prevalence of sensitization and allergies within these 2 groups was then established and compared. The two groups were comparable in terms of gender, smoking habits, job classification, work-related symptoms and the number of individuals who had atopy. In 2009, the prevalence of sensitization to latex was statistically significantly lower than in 1998 (4.5 vs. 14.1%). Allergy to latex was also established a statistically significantly fewer number of times in 2009 than in 1998 (2.8 vs. 9.8%). This same trend could be observed in the subgroup that participated both years (n = 49). Individuals with an atopic constitution had a statistically significant higher risk of developing hypersensitivity to natural latex; the risk of developing an allergy to latex was also higher, but not significantly. After the study in 1998, the introduction of sterile, powder-free latex gloves very likely led to a decline in the prevalence of sensitization and allergy to natural latex in 2009.


Rural Hospital Closures in Tennessee: Centering Community Residents' Voices to Identify Public Health Ethical Issues and Inform Policy Strategies.
The US is witnessing rapid hospital closures in rural communities, with devastating consequences for community residents beyond decreased access to health care services. Hospital closures have been associated with outmigration of younger generations due to loss of employment opportunities and economic decline, and with creating uncertainty and a sense of powerlessness among residents. While great efforts have been undertaken to document the effects of hospital closures on health care access, particularly during the COVID-19 epidemic, limited attention has been given to the public health ethics associated with dismantling health care for populations in greatest need. Drawing on the narratives of community stakeholders and residents, several themes evolved around processes, structures, and spillover effects of hospital closures on their daily lives, including decision making processes of when and how to close hospitals. Concerns arose regarding lack of transparency and disregard for alternative health care services to meet the needs of rural communities. The researchers analyzed participants' stories using the six core values of the American Public Health Association's code of ethics to determine the extent to which the multilevel crisis emerging from rural hospital closures contradicts the public health ethical responsibility of ensuring access to health care in rural communities. Centering the voices of rural community stakeholders and residents is critical to inform and guide public health strategies and in turn address health care needs of rural communities.


Tyrosine kinase Fyn promotes osteoarthritis by activating the β-catenin pathway.
To investigate the role of tyrosine kinase Fyn in the development of osteoarthritis (OA) and the underlying mechanisms, and to define whether targeting Fyn could prevent OA in mice. Cartilage samples from normal and aged mice were analysed with proteome-wide screening. Fyn expression was examined with immunofluorescence in human and age-dependent or experimental mouse OA cartilage samples. Experimental OA in Fyn-knockout mice was induced by destabilisation of the medial meniscus. Primary cultured mouse chondrocytes were treated with proinflammatory cytokine interleukin-1β. The inhibitor of Src kinase family, AZD0530 (saracatinib), and inhibitor of Fyn, PP1, were used to treat experimental OA in mice. Fyn expression was markedly upregulated in human OA cartilage and in cartilage from aged mice and those with post-traumatic OA. Fyn accumulates in articular chondrocytes and interacts directly with and phosphorylates β-catenin at Tyr142, which stabilises β-catenin and promotes its nuclear translocation. The deletion of Fyn effectively delayed the development of post-traumatic and age-dependent OA in mice. Fyn inhibitors AZD0530 and PP1 significantly attenuated OA progression by blocking the β-catenin pathway and reducing the levels of extracellular matrix catabolic enzymes in the articular cartilage. Fyn accumulates and activates β-catenin signalling in chondrocytes, accelerating the degradation of the articular cartilage and OA development. Targeting Fyn is a novel and potentially therapeutic approach to the treatment of OA.


A double-decomposition based parallel exact algorithm for the feedback length minimization problem.
Product development projects usually contain many interrelated activities with complex information dependences, which induce activity rework, project delay and cost overrun. To reduce negative impacts, scheduling interrelated activities in an appropriate sequence is an important issue for project managers. This study develops a double-decomposition based parallel branch-and-prune algorithm, to determine the optimal activity sequence that minimizes the total feedback length (FLMP). This algorithm decomposes FLMP from two perspectives, which enables the use of all available computing resources to solve subproblems concurrently. In addition, we propose a result-compression strategy and a hash-address strategy to enhance this algorithm. Experimental results indicate that our algorithm can find the optimal sequence for FLMP up to 27 activities within 1 h, and outperforms state of the art exact algorithms.


Ductal carcinoma in situ of the breast in Israeli women treated by breast-conserving surgery followed by radiation therapy.
Lumpectomy followed by radiation therapy (RT) has become an accepted local management strategy for patients with small, mammographically detected ductal carcinoma in situ (DCIS) of the breast. The aim of this analysis is to describe control rates and patterns of relapse in a cohort of Israeli women with mammographically detected DCIS treated at a single medical center. The files of 107 consecutive patients with DCIS were retrieved from the cancer registry of the unit of RT. All women underwent lumpectomy followed by definitive RT, administered in conventional dose fractionation regimens. Oral tamoxifen, 20 mg/ day, was prescribed to all but 2 patients with positive receptors. Within a median follow-up time of 52 months, no local recurrence of any breast tumor was found. There was no correlation between event-free survival and tumor size, focality, grading, hormone receptor status, administration of adjuvant hormonal therapy, timing of RT, and RT boost delivery. The 8-year overall survival, disease-free-survival, and event-free survival were 100, 100, and 87%, respectively. The results reported herein are consistent with short-term and intermediate-term outcomes that are better than the reported benchmarks from prospective randomized trials. Although this could reflect selection factors at a single institution, it is also plausible that a genetically distinct disease is present in this local population.


Imidazole antifungals Miconazole and Econazole induce apoptosis in mouse lymphoma and human T cell leukemia cells: regulation by Bcl-2 and potential role of calcium.
We have recently reported that thapsigargin (TG), a specific endoplasmic reticulum (ER)-associated Ca(2+)-ATPase inhibitor, induces apoptosis in mouse lymphoma cells. In view of recent evidence that the imidazole antifungals econazole (EC) and miconazole (MC) inhibit TG-sensitive Ca(2+)-ATPase activity in normal rat thymocytes, we investigated the effect of these agents on intracellular Ca(2+) homeostasis and cell survival in WEHI7.2 mouse lymphoma cells and human CEMT-cell leukemia cells. In this report, we demonstrate that MC treatment releases Ca(2+) from the TG-sensitive ER pool of WEHI7.2 cells. MC induced apoptosis, based on morphological and biochemical criteria, and on inhibition by the Bcl-2 oncogene. Moreover, intracellular Ca(2+) changes induced by MC treatment were inhibited by overexpression of Bcl-2. In addition to inducing cell death in WEHI7.2 cells, MC induced apoptosis in the glucocorticoid sensitive and resistant human T-cell leukemia lines, CEM-C7 and CEM-C1 respectively, in normal thymocytes and in normal lymphocytes. Based on their apoptosis-inducing activity, imidazole derivatives should be explored as potential immunosuppressive and/or chemotherapeutic agents.


Oscillatory deviations from Matthiessen's rule due to interacting dislocations.
We theoretically examine the validity of Matthiessen's rule caused by strong dislocation-dislocation interaction using a fully quantized dislocation field, where its degree of deviation is quantified at arbitrary electron energy, dislocation-electron and dislocation-dislocation distances and interaction strengths. Contrary to intuition, we show that the electron relaxation rate deviates from the Matthiessen's rule in an oscillatory way as a function of inter-dislocation distance, instead of monotonically. In addition, we show quantitatively that the deviation is larger in a material with lower mass density, higher Poisson ratio and higher elastic moduli. This study could serve as a computational tool to investigate the electronic behavior of a highly-dislocated system at a full quantum field theoretical level.


Blocking endothelin-1-receptor/β-catenin circuit sensitizes to chemotherapy in colorectal cancer.
The limited clinical response to conventional chemotherapeutics observed in colorectal cancer (CRC) may be related to the connections between the hyperactivated β-catenin signaling and other pathways in CRC stem-like cells (CRC-SC). Here, we show the mechanistic link between the endothelin-1 (ET-1)/ET-1 receptor (ET-1R) signaling and β-catenin pathway through the specific interaction with the signal transducer β-arrestin1 (β-arr1), which initiates signaling cascades as part of the signaling complex. Using a panel of patient-derived CRC-SC, we show that these cells secrete ET-1 and express ETAR and β-arr1, and that the activation of ETAR/β-arr1 axis promotes the cross-talk with β-catenin signaling to sustain stemness, epithelial-to-mesenchymal transition (EMT) phenotype and response to chemotherapy. Upon ETAR activation, β-arr1 acts as a transcription co-activator that binds β-catenin, thereby promoting nuclear complex with β-catenin/TFC4 and p300 and histone acetylation, inducing chromatin reorganization on target genes, such as ET-1. The enhanced transcription of ET-1 increases the self-sustained ET-1/β-catenin network. All these findings provide a strong rationale for targeting ET-1R to hamper downstream β-catenin/ET-1 autocrine circuit. Interestingly, treatment with macitentan, a dual ETAR and ETBR antagonist, able to interfere with tumor and microenvironment, disrupts the ET-1R/β-arr1-β-catenin interaction impairing pathways involved in cell survival, EMT, invasion, and enhancing sensitivity to oxaliplatin (OX) and 5-fluorouracil (5-FU). In CRC-SC xenografts, the combination of macitentan and OX or 5-FU enhances the therapeutic effects of cytotoxic drugs. Together, these results provide mechanistic insight into how ET-1R coopts β-catenin signaling and offer a novel therapeutic strategy to manage CRC based on the combination of macitentan and chemotherapy that might benefit patients whose tumors show high ETAR and β-catenin expression.


Effects of vasopressin and bradykinin on anion transport by the rat cortical collecting duct. Evidence for an electroneutral sodium chloride transport pathway.
Our previous studies in cortical collecting ducts isolated from rat kidneys have shown that vasopressin increases both sodium absorption and potassium secretion, while bradykinin inhibits sodium absorption without affecting potassium transport. To determine which anions are affected by these agents, we perfused cortical collecting ducts from rats treated with deoxycorticosterone and measured net chloride flux, net bicarbonate flux (measured as total CO2), transepithelial voltage, and the rate of fluid absorption. Arginine vasopressin (10(-10) M in the peritubular bath) caused a sustained sixfold increase in net chloride absorption and a two- to threefold increase in the magnitude of the lumen negative transepithelial voltage. Before addition of vasopressin, the tubules secreted bicarbonate. Vasopressin abolished the bicarbonate secretion, resulting in net bicarbonate absorption (presumably due to proton secretion) in many tubules. Bradykinin (10(-9) M added to the peritubular bath) caused a reversible 40% inhibition of net chloride absorption, but did not affect the transepithelial voltage or the bicarbonate flux. We concluded: (a) that arginine vasopressin stimulates absorption of chloride and inhibits bicarbonate secretion (or stimulates proton secretion) in the rat cortical collecting duct; and (b) that bradykinin inhibits net chloride absorption in the rat cortical collecting duct without affecting transepithelial voltage or bicarbonate flux. Combining these results with the previous observations on cation fluxes described above, we conclude that bradykinin inhibits electroneutral NaCl absorption (or stimulates electroneutral NaCl secretion) in the rat cortical collecting duct.


Accumulation of sulfoquinovosyl-1-O-dihydroxyacetone in a sulfolipid-deficient mutant of Rhodobacter sphaeroides inactivated in sqdC.
The biosynthesis of the sulfolipid sulfoquinovosyl diacylglycerol in the purple bacterium Rhodobacter sphaeroides requires at least four genes:sqdA, sqdB, sqdC, and sqdD. As part of our strategy aimed at the elucidation of the function of the different sqd gene products, we insertionally inactivated sqdC of R. sphaeroides. The resulting sqdC null mutant showed only a 90% reduction in sulfolipid content. Apparently, the sqdC gene product is required for optimal sulfolipid biosynthesis, but either catalyzes no essential reaction in the pathway or can be functionally replaced to a certain extent by a different protein. The mutant accumulated a 35S-labeled compound that was purified to homogeneity from cell extracts. Matrix-assisted laser desorption mass spectrometry and nuclear magnetic resonance spectroscopy provided conclusive structural evidence to identify the compound as alpha-D-sulfoquinovosyl-1-O-dihydroxyacetone that exists in two interconvertible, keto and hemiacetal forms. Incubation of wild-type protein extracts with the labeled compound did not result in the incorporation into sulfolipid as would be expected for an intermediate of the pathway. Based on our results we propose that the sqdC gene product mediates the substrate specificity of the UDP-sulfoquinovose:diacylglycerol sulfoquinovosyltransferase that is encoded by sqdD and that catalyzes the final reaction of sulfolipid biosynthesis.


Controlled clinical trial of repeated prefrontal tDCS in patients with chronic minimally conscious state.
To assess the effects of repeated transcranial direct current stimulation (tDCS) sessions on the level of consciousness in chronic patients in minimally conscious state (MCS). In this randomized double-blind sham-controlled crossover study, we enrolled 16 patients in chronic MCS. For 5 consecutive days, each patient received active or sham tDCS over the left prefrontal cortex (2 mA during 20 min). Consciousness was assessed with the Coma Recovery Scale-Revised (CRS-R) before the first stimulation (baseline), after each stimulation (day 1-day 5) and 1 week after the end of each session (day 12). A treatment effect (p = 0.013; effect size = 0.43) was observed at the end of the active tDCS session (day 5) as well as 1 week after the end of the active tDCS session (day 12; p = 0.002; effect size = 0.57). A longitudinal increase of the CRS-R total scores was identified for the active tDCS session (p < 0.001), while no change was found for the sham session (p = 0.64). Nine patients were identified as responders (56%). Our results suggest that repeated (5 days) left prefrontal tDCS improves the recovery of consciousness in some chronic patients in MCS, up to 1 week after the end of the stimulations.


Neurotransmitter markers of depression.
The role of antidepressants in bringing about adaptive changes in peripheral and central neurotransmitter receptors is briefly reviewed and extended to show how changes in platelet and lymphocyte adrenoceptor and serotonin receptor activity may correlate with the depressed state and normalise following effective treatment. By contrast, the 3H-imipramine binding sites on the platelet membrane do not change following successful treatment and may therefore reflect a trait-dependent (genetic) change. The neuroendocrine markers, such as the dexamethasone suppression test (DST), have the advantage over the receptor markers in that they require less sophisticated laboratory facilities. It is concluded that a better insight into the aetiology and progress of depression may be gained by combining receptor markers with such neuroendocrine markers as the DST.


[Evaluation of multidisciplinary treatment involving chemotherapy with cis-diamminedichloroplatinum, bleomycin (peplomycin) and 5-fluorouracil for advanced esophageal carcinoma].
Twelve patients with unresectable squamous cell carcinoma of the esophagus were treated with a combination chemotherapy regimen consisting of cis-diamminedichloroplatinum (CDDP), bleomycin (BLM) or peplomycin (PEP), and 5-fluorouracil (5-FU). Ten of them received radiation therapy additionally. CDDP was administered once every 4 weeks at a dose of 50 mg/m2. Methylprednisolone of 250 mg was given intravenously 4 times at the same day with infusion of CDDP. BLM or PEP was administered intravenously at a dose of 20 mg/m2 every 2 weeks and 5-FU was administered at a dose of 330 mg/m2 on days 1-5, 15-19, and afterwards every 4 weeks. All patients received at least two courses of chemotherapy. All of them were evaluable. Complete and partial responses were obtained in one and eight cases, respectively. Responsive rate was 75.0%. The median duration of response was 17.0 weeks. The median duration of survival was 44.0 weeks in all patients, 46.1 weeks in responders and 17.9 weeks in non-responders. Nausea, vomiting, leucopenia, fever, nephrotoxicity and radiation esophagitis were observed as side effects but most of them were mild and well tolerated. In conclusion, this regimen was considered to be very useful as the chemotherapy for primary esophageal carcinoma.


Effects of semantically related and unrelated contexts on recognition memory of different-aged adults.
Two experiments were conducted to examine adult age differences in the use of context information. In Experiment 1, the encoding of contextually influenced semantic features was examined, and the encodings of target words by both young and old adults were observed to be influenced by semantic information provided by the context. Older adults did make more semantic confusion errors, however, suggesting less distinctive encoding. Verbal ability also influenced performance, with the difference between ability groups being similar to that between age groups. In Experiment 2, target words were presented in semantically unrelated contexts, and older adults were found not to encode contextual information in this situation. It is hypothesized that the older adults' context effects in Experiment 1 were due to automatic activation of nonspecific word meaning features due to the relation between target and context. When no such familiar context existed, the older adults were less likely to use context information.


ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells.
Liver cancer stem cells (CSCs) have been identified and shown to have self-renewal and differentiation properties; however, the biology of these hepatic CSCs remains largely unknown. Here, we analyzed transcriptome gene expression profiles of liver CSCs and non-CSCs from hepatocellular carcinoma (HCC) cells lines and found that the transcription factor (TF) ZIC2 is highly expressed in liver CSCs. ZIC2 was required for the self-renewal maintenance of liver CSCs, as ZIC2 depletion reduced sphere formation and xenograft tumor growth in mice. We determined that ZIC2 acts upstream of the TF OCT4 and that ZIC2 recruits the nuclear remodeling factor (NURF) complex to the OCT4 promoter, thereby initiating OCT4 activation. In HCC patients, expression levels of the NURF complex were consistent with clinical severity and prognosis. Moreover, ZIC2 and OCT4 levels positively correlated to the clinicopathological stages of HCC patients. Altogether, our results indicate that levels of ZIC2, OCT4, and the NURF complex can be detected and used for diagnosis and prognosis prediction of HCC patients. Moreover, these factors may be potential therapeutic targets for eradicating liver CSCs.


Synthesis, crystal structure, optical and thermal properties of lanthanide hydrogen-polyphosphates Ln[H(PO3)4] (Ln = Tb, Dy, Ho).
Lanthanide hydrogen-polyphosphates Ln[H(PO3)4] (Ln = Tb, Dy, Ho) were synthesised as colourless (Ln = Tb, Dy) and light pink (Ln = Ho) crystalline powders by reaction of Tb4O7/Dy2O3/Ho2O3 with H3PO3 at 380 °C. All compounds crystallise isotypically (P2(1)/c (no. 14), Z = 4, a(Tb) = 1368.24(4) pm, b(Tb) = 710.42(2) pm, c(Tb) = 965.79(3) pm, β(Tb) = 101.200(1)°, 3112 data, 160 parameters, wR2 = 0.062, a(Ho) = 1363.34(5) pm, b(Ho) = 709.24(3) pm, c(Ho) = 959.07(4) pm, β(Ho) = 101.055(1)°, 1607 data, 158 parameters, wR2 = 0.058). The crystal structure comprises two different infinite helical chains of corner-sharing phosphate tetrahedra. In-between these chains the lanthanide ions are located, coordinated by seven oxygen atoms belonging to four different polyphosphate chains. Vibrational, UV/Vis and fluorescence spectra of Ln[H(PO3)4] (Ln = Tb, Dy, Ho) as well as Dy[H(PO3)4]:Ln (Ln = Ce, Eu) and the magnetic and thermal behaviour of Tb[H(PO3)4] are reported.


Accuracy of formant measurement for synthesized vowels using the reassigned spectrogram and comparison with linear prediction.
This brief report describes a small study which was undertaken with nine synthetic vowel tokens, in an effort to demonstrate the validity of the reassigned spectrogram as a formant measurement tool. The reassigned spectrogram's performance is also compared with that of a typical pitch-asynchronous linear predictive analysis and is found to be superior. In this study, reassigned spectrograms were further processed to highlight the formants and then were used to measure these synthetic vowel formants generally to within 0.5% of their known true values, far surpassing the accuracy of a typical linear predictive analysis procedure which was inaccurate by as much as 17%. The overall accuracy of reassigned spectrographic formant measurement is thus demonstrated in these cases.


Arrest of mycobacterial phagosome maturation is caused by a block in vesicle fusion between stages controlled by rab5 and rab7.
Mycobacterium tuberculosis and the closely related organism Mycobacterium bovis can survive and replicate inside macrophages. Intracellular survival is at least in part attributed to the failure of mycobacterial phagosomes to undergo fusion with lysosomes. The transformation of phagosomes into phagolysosomes involves gradual acquisition of markers from the endosomal compartment. Members of the rab family of small GTPases which confer fusion competence in the endocytic pathway are exchanged sequentially onto the phagosomal membranes in the course of their maturation. To identify the step at which the fusion capability of phagosomes containing mycobacteria is compromised, we purified green fluorescent protein-labeled M. bovis BCG phagosomal compartments (MPC) and compared GTP-binding protein profiles of these vesicles with latex bead phagosomal compartments (LBC). We report that the MPC do not acquire rab7, specific for late endosomes, even 7 days postinfection, whereas this GTP-binding protein is present on the LBC within hours after phagocytosis. By contrast, rab5 is retained and enriched with time on the MPC, suggesting fusion competence with an early endosomal compartment. Prior infection of macrophages with M. bovis BCG also affected the dynamics of rab5 and rab7 acquisition by subsequently formed LBC. Selective exclusion of rab7, coupled with the retention of rab5 on the mycobacterial phagosome, may allow organisms from the M. tuberculosis complex to avert the usual physiological destination of phagocytosed material.


The use of suction-assisted surgical extraction of moderate and large lipomas: long-term follow-up.
Solitary lipomas and familial multiple lipomatosis are the most common benign tumors and are very well encapsulated. They are very slow growing and have the potential for recurrence if incompletely excised and a very remote chance for malignant changes. These can be freed from surrounding tissue without difficulty, but because of the fibrous nature of the capsule, its violation is more likely with suction technique and may result in an inadequate resection, possibly leading to recurrence. Furthermore, liposuction alone will not allow histopathological study of the swellings. Therefore, we report here the treatment of moderate (>4-10 cm) and large (>10 cm) lipomas with liposuction-assisted surgical extraction of the capsule via the same wound (1 cm in length). This capsule extraction is aimed at avoiding recurrence and evaluating the histopathological nature of these swellings. 16 patients (nine men and seven women) presented with solitary lipomas (in 11 patients) and multiple lipomas (in five patients) have been successfully treated. Methods involved 1-cm incision for both liposuction and surgical removal of the capsule. Another 1-cm counter-incision may be needed in case of large size lipomas. High patient satisfaction was achieved because of the good cosmetic results due to the small postoperative residual scar and the smooth postoperative course. There has been no recorded recurrence in six years postoperative followup.


Safely treating hypokalaemia in high dependency cardiac surgical patients.
In Australia, there were national issues on the use of potassium ampoules (resulting in patient deaths), which led to the removal of the ampoules from clinical areas. A decision was made by the Medication Safety Committee at a metropolitan Melbourne hospital to remove potassium ampoules from ward areas as part of the establishment of a hospital-wide potassium guideline. As a result, the nurses in the cardiothoracic ward Practice Review Committee identified the need to review the proposed practice of treating hypokalaemia with 30 mmol of potassium chloride (KCL) in 1000 mL over an extended period in postoperative cardiothoracic patients. The challenge was to develop a practice to safely administer intravenous KCL in fluid restricted patients in addition to the hospital guidelines to prevent hypokalaemic-induced cardiac dysrhythmias. A literature search revealed there were no clear or uniform approaches to guide our practice in addressing this clinical problem. The Practice Review Committee developed a KCL administration guideline based on a review of the available literature. The Practice Review Committee developed a ward-based guideline that addressed infusion concentration, duration of administration, responsiveness of nurses to severity of hypokalaemia and the evaluation of treatment by measuring serum potassium after replacement. This ward-based guideline was based on benchmarking from similar institutions and relevant literature. The review process provided an opportunity for the staff to critique their practice to improve patient care and allowed regular evaluation of the implemented practice guideline. The ward-based guideline required a revision as patients' renal function was not being taken into consideration prior to potassium infusions being administered. The implementation of the ward-based guideline into practice has been well received by the staff as it has allowed consistent practice and timely treatment of hypokalaemia.


Two Medicinal Plants (Alkanna trichophila and Convolvulus galaticus) from Turkey: Chemical Characterization and Biological Perspectives.
The aim of the present study was to quantify selected phenolic compounds, determine antioxidant activity and enzyme inhibitory effects of the aerial parts of Alkanna trichophylla Hub.-Mor. (A. trichophylla) and Convolvulus galaticus Rost.ex Choisy (C. galaticus) extracts prepared by homogenizer-assisted extraction (HAE), maceration (MAC) and infusion techniques. This is the first time such study has been designed to validate the phytochemical composition and bioactivity of these plants. Multivariate analysis was conducted on collected data. Rutin and caffeoylquinic acid derivatives were the most significant compounds in A. trichophylla and C. galaticus, respectively. The highest antioxidant activity of A. trichophylla was mostly exhibited by HAE/methanolic extracts as determined by DPPH, ABTS, FRAP (51.39, 112.70 and 145.73 mg TE/g, respectively) and phosphomolybdenum (2.05 mmol TE/g) assays. However, significant antioxidant activities varied within the extracts of C. galaticus. HAE/methanolic extract of A. trichophylla significantly depressed AChE (2.70 mg GALAE/g), BChE (5.53 mg GALAE/g) and tyrosinase (26.34 mg KAE/g) activities and that of C. galaticus inhibited AChE (2.04 mg GALAE/g), tyrosinase (31.25 mg KAE/g) and α-amylase (0.53 mmol ACAE/g) activities significantly. We concluded that HAE was the most efficient extraction technique as high yield of compounds and promising bioactivities were recorded from extracts prepared. Multivariate analysis showed that types of solvents influenced recovery of compounds and biological activities. This research study can be used as one methodological starting point for further investigation on these plants as all results are clearly promising and open the door to further research challenges such as cytotoxicity evaluation, molecular docking analysis, and more screening of pharmacological actions.


Therapeutic trial with glycine in myoclonus.
We investigated the therapeutic effects of glycine in seven patients with various forms of myoclonus. The initial phase was an open label trial. If benefit was seen in any patient, a double-blind substitution of placebo was carried out to determine if the benefit was due, in fact, to glycine. The dosage of glycine was initiated at 600 mg/day and was increased gradually until a maximum dosage of 6,000 mg/day was reached. This dosage was maintained for at least 6 weeks before lack of efficacy was declared. No improvement was seen in four patients. One patient reported improvement, but he discontinued the drug because of adverse effects encountered with the use of a concomitant medication and before he could be tested in a double-blind crossover phase. Two other patients also noticed improvement, but these improvements were not validated in the crossover phase. There were no adverse effects associated with glycine. Plasma glycine levels peaked at 30 min and returned to normal 1.5-h after 1 g of glycine.p.o. Cerebrospinal fluid (CSF) glycine levels did not change during treatment, suggesting inadequate penetration into the central nervous system of glycine at the dosage used.


Management of lactational breast abscesses.
The purpose of the present prospective study was to compare incision and drainage against needle aspiration for the treatment of breast abscesses in lactating women. During the 3-year study period, patients with breast abscesses were randomized 1:1 to undergo either incision and drainage (23 patients) or needle aspiration (22 patients). Ultrasound guidance was not used for any of these patients. Age, parity, localization of abscess, whether or not nipples were cracked, duration of symptoms and lactation, abscess diameter, pus culture results, breast infection history during any previous period of lactation, healing time, recurrence, cosmetic outcome in the case of incision and drainage, and volume of pus removed and number of aspirations needed in the case of aspiration were recorded. The treatment value of each of these techniques was investigated. Student's t-test, Fisher's exact test, a Chi-square test and the Mann-Whitney U-test were used for statistical analysis. In the incision and drainage group all patients were treated successfully, but 1 patient (4%) had a recurrence 2 months after complete healing and 16 patients (70%) in this group were not pleased with the cosmetic outcome. In the needle aspiration group, overall 3 patients were treated with a single aspiration and 10 patients (45%) with multiple aspirations, but 9 patients (41%) did not heal following needle aspiration and subsequently required incision and drainage in addition. No recurrences were observed in the needle aspiration group during the follow-up period. The risk factors for failure of needle aspiration for breast abscesses were abscesses larger than 5 cm in diameter, unusually large volume of aspirated pus, and delay in treatment. In conclusion, breast abscesses smaller than 5 cm in diameter on physical examination can be treated with repeated aspirations with good cosmetic results. Incision and drainage should be reserved for use in patients with larger abscesses.


Mycoplasma Infection as a cause of Persistent Fever after Intravenous Immunoglobulin Treatment of Patients with Kawasaki Disease: Frequency and Clinical Impact.
Mycoplasma is a common cause of respiratory infections and may require differential diagnosis from Kawasaki disease (KD). In this study, we investigated the frequency and clinical manifestations of mycoplasma infection in patients with KD. Medical records of 375 in-patients admitted for treatment during the acute stage of KD, were collected, and reviewed retrospectively. Of these patients, 152 (40.5%) were also tested for recent mycoplasma infection. Patients with positive results (anti-mycoplasma IgM Ab >1:640 or cold agglutinin >1:64) were designated as the case group (n = 37, 24.3%) whereas those with negative results were designated as the control group (n = 115, 75.7%). Clinical findings of the two groups were compared. Patients in the case group were older than those in the control group (mean age, 48.2 ± 32.1 months, vs. 31.7 ± 21.7 months; P = 0.001). There were significant differences between the case and control groups in the changes in the extremities (78.3% vs. 57.4%, respectively; P = 0.031), and in fever duration (6.5 ± 2.5 days vs. 5.4 ± 1.5 days; P = 0.047). Of the 37 patients with positive mycoplasma testing, 7 (18.9%) had persistent fever even after the symptoms and signs of systemic inflammation (acute phase of KD) had been resolved. These patients were positive for mycoplasma infection during further evaluation of persistent fever, and all of them responded to macrolide antibiotics. We found that mycoplasma infection is somewhat related to KD. When fever persists after resolution of the acute stage of KD, mycoplasma infection may be considered as a possible cause of fever in preschool-aged children.


[What would happen if day care centers closed?].
To determine the possible association between the decrease in emergency episodes and the strike in day care centers in Vitoria (Spain) in the autumn of 2004, which affected 86 % of children attending these centers. We performed a retrospective observational study. In Vitoria, there were 27404 children under the age of 14 in 2004; of these, 5890 were under the age of 3 years. The day care centers on strike affected 25.4 % of the latter. We compared emergency episodes and hospital admissions during the strike (September to November, 2004) with those occurring in the previous 5 years. To contrast the hypothesis, a comparison of proportions was used with statistical significance set at p < 0.005. A significant decrease (rate x 1000 inhabitants) was observed in the number of emergency episodes in children under 3 years old in two of the three months of the strike (October and November, p < 0.01). No significant differences were observed in emergency rates in children aged more than 3 years old, or in hospital admissions in all ages. These data suggest that children attending day care centers have a higher risk of catching banal diseases (which do not require hospital admission and are probably infectocontagious illnesses) than children not attending these centers, thus increasing demand for pediatric emergency services. Since the solution does not lie in closing day care centers, hygienic and sanitary measures should be maximized in these centers.


Gendered dis/ability: perspectives from the treatment of psychiatric casualties in Russia's early twentieth-century wars.
The historiography on disability and gender in the West suggests an association between 'masculine' ability and 'feminine' disability. In contrast, Russia's early twentieth-century literature on the treatment of mentally-ill soldiers reveals a broader range of choices in ascriptions of gender and dis/ability. While conceptions of 'masculine' ability and 'feminine' disability existed in Russia, these two permutations of gender and dis/ability were neither strictly opposed in professional medical literature, nor were they the only available options. Physicians and patients most intimately associated with psychiatric casualties in Russia's wars also considered certain individuals to be masculine and disabled, as well as feminine and able. This article discusses and interprets these issues and concludes by exploring some of the possible political and cultural reasons why understandings of gender and disability proved more flexible in Russia than in the West.


Crystallization and preliminary X-ray analysis of wild-type and K272A mutant glutamate 1-semialdehyde aminotransferase from Synechococcus.
Crystals of the pyridoxal-5'-phosphate dependent enzyme glutamate-1-semialdehyde aminotransferase (EC 220.127.116.11) from Synechococcus have been grown from polyethylene glycol solutions. The wild-type enzyme crystallizes in space group P2(1)2(1)2(1), with cell dimensions a = 68.4 A, b = 108.0 A, c = 122.6 A. The inactive mutant in which the cofactor-binding lysine 272 residue is replaced by alanine (K272A) gives monoclinic crystals of space group P2(1) with cell dimensions a = 67.1 A, b = 108.6 A, c = 124.5 A and beta = 115.7 degrees. These crystal forms diffract to 2.4 A and 2.7 A resolution, respectively.


Understanding Why Children Commit Scale Errors: Scale Error and Its Relation to Action Planning and Inhibitory Control, and the Concept of Size.
Scale error is a phenomenon where young children attempt to perform inappropriate actions on miniature object without considering the actual size of the object. The present study examined two hypotheses on what factors contribute to the occurrence of scale errors, focusing on the following possible factors: action planning and inhibitory control, and concept of size. Thus, we hypothesize that scale errors derived from either immaturity of their action planning and inhibitory control abilities or understanding of size concepts. The results revealed that the concept of size was significantly negatively associated with the occurrence of scale errors. However, action planning and inhibitory control were not significantly associated with the occurrence of scale errors. These results suggest that scale errors may arise from a misunderstanding of size concepts.


Declined Live Birth Rate from in vitro Fertilization Fresh Cycles Performed During Chinese New Year Holiday Season.
This study aims to investigate the impact of the Chinese New Year (CNY) holiday season on the outcomes of In Vitro Fertilization (IVF) fresh embryo transfer cycles. This retrospective study analyzed 4688 patients who received their first IVF fresh cycle attempt between January 2017 and October 2021. Of these, 4449 women underwent IVF during non-holiday seasons, while 239 women were treated during the CNY holiday season. The study included women who underwent IVF treatment during the specified time frame. The primary outcome was the live birth rate (LBR). The study found that the LBR of IVF performed during the CNY holiday season was 32.22%, which is significantly lower than that of the non-holiday season (43.38%, p<0.001). Multivariate logistic regression analysis showed that the CNY holiday season (OR=0.62, 95% CI 0.47-0.82, p=0.001) was an independent factor associated with the live birth rate. Propensity score matching (PSM) data analysis showed that the LBR in the CNY holiday season group was 31.78% compared to 42.64% in the non-holiday season group (p=0.005). Inverse probability of treatment weighting (IPTW) data also indicated that the CNY holiday season had a lower LBR than the non-holiday season (OR=0.64, 95% CI 0.47-0.87, p=0.005). IVF performed during the CNY holiday season results in a lower live birth rate, potentially indicating that certain lifestyle adjustments during this period, such as unhealthy dietary, tobacco and alcohol usage, sleep disruption, and emotional stress experienced could have some influence on the outcomes.


Total synthesis of the cystatin alpha gene and its expression in E. coli.
A gene encoding cystatin alpha has been chemically synthesized, cloned and expressed in E. coli. The gene of 318 base pairs was assembled by enzymatic ligation of 19 oligonucleotides and cloned into a pBR322-derived expression plasmid down stream of the tac promoter. The expression product of the synthetic gene has been purified by Sephadex G-50 column chromatography and shown to have the same properties as those of the authentic protein isolated from rat epidermis.


Hypermethylated WNT10A and its clinical significance in colorectal cancer.
Colorectal cancer (CRC) is a heterogeneous disease in which unique subtypes are characterized by distinct genetic and epigenetic alterations. DNA methylation, a well-documented epigenetic modification, is a promising biomarker for the diagnosis and prognosis of cancers, including CRC. WNT10A is a member of the Wnt family. It belongs to the Wnt signaling pathway and is involved in CRC. However, studies regarding the methylation and expression of WNT10A in CRC are limited. In the current study, we analyzed the methylation status of WNT10A in 146 patients with CRC and normal controls. These samples were classified into two groups. The first group was an initial discovery set (i.e., fresh tissue samples from 40 patients with CRC and adjacent normal control samples). The second group was an independent validation set (i.e., formalin-fixed and paraffin-embeded [FFPE] samples from 106 patients with CRC and cutting edge tissues). The results showed a higher level of WNT10A hypermethylation of in CRC samples than in controls (Fresh tissue cohort: P = 2.8E-5; FFPE cohort: P = 3.6E-4).This finding was verified by WNT10A methylation data from The Cancer Genome Atlas portal (TCGA) (P = 1.9E-83). Subgroup analysis of clinical characteristics showed a higher WNT10A methylation level in elder patients (aged > 60 y) (P = 0.037) and, patients with distant metastasis (P = 0.033), rectal cancer (P = 0.03), and mucinous adenocarcinoma (P = 0.02). Furthermore, TCGA RNAseq data demonstrated lower WNT10A expression in patients with CRC than in controls (P = 4.0E-3) and showed a negative correlation between expression and methylation (r = -0.37, P = 5.7E-13). Moreover, the efficiency of WNT10A methylation for CRC diagnosis was analyzed in both cohorts of the present study and the TCGA cohorts, which indicated the potential use of WNT10A methylation as a tool for diagnosis of CRC.


Risk factors predicting intra-abdominal desmoids in familial adenomatous polyposis: a single centre experience.
Desmoids are myofibroblastic proliferations occurring in 15% of patients with familial adenomatous polyposis (FAP), 70% being intra-abdominal desmoids (IAD). Since the morbidity and mortality due to desmoids is almost entirely attributable to IAD, we aimed to identify specifically risk factors predicting IAD development in FAP. We undertook a retrospective review of our institutional database. Multivariate analysis was performed, and hazard ratios (HR) calculated for variables including female gender, 3' APC mutation, surgical intervention for FAP (colectomy with ileo-rectal anastomosis or restorative proctocolectomy), age at surgery and family history (FH) of desmoids. Of the 558 patients analysed, 49 (9%) developed IAD; 22 (4%) diagnosed intra-operatively and 27 (5%) developing over a median post-operative period of 34 (7-120) months. 75% of IAD had developed before age 40. A 3' APC mutation (HR 5.2, 95% CI 2.1-13.3, P = 0.001), positive FH (HR 2.5, 95% CI 1.4-4.6, P = 0.003) and female gender (HR 1.9, 95% CI 1.0-3.5, P = 0.04) were found to be predictive of IAD development. No significant difference in IAD risk was detected between the type of surgical intervention (P = 0.37) or age at surgery (P = 0.29). Our analysis confirms 3' APC mutation to be the most significant risk factor for IAD development. The independent association between positive FH and IAD risk suggests the existence of modifier genes, independent of the APC genotype-phenotype correlation. Few of these risk factors can be meaningfully modified. Delaying prophylactic surgery may be appropriate in female patients with a 3' APC mutation and attenuated polyposis.


[Changes in the expression of rat hepatic lipid metabolism related genes in response to burn wound sepsis as assessed by DNA arrays].
To examine the expression profile of lipid metabolism-related genes in liver of scalded rats with wound sepsis, and to analyze its significance. Sixty male Wistar rats with 30% TBSA full-thickness scald wound on the back were enrolled in the study and randomly divided into wound sepsis group (n = 30) and control group (n = 30, with scald). Pseudomonas aeruginosa was inoculated to the wounds in sepsis group. Corresponding indices were determined to verify the diagnosis of wound sepsis. The rats were sacrificed and fresh liver tissues were obtained at 96 post-scald hours (PSH). Total RNA of liver was isolated with Trizol and the different expression of lipid metabolism related genes in response to burn wound sepsis was assessed by DNA microarray. By comparing expression profile of the two groups, totally 47 genes were observed to be differentially expressed in rat hepatic tissues, among them 9 genes were related to lipid metabolism. Among them, those which were upregulated were genes in relation with transportation and activation of fatty acid, and those downregulated were genes related in providing energy for fatty acid oxidation in mitochondria. The occurrence of wound sepsis in scalded rats can induce changes in the expression of hepatic lipid metabolism related genes in hepatic tissues, and aggravate


Factors Influencing the Regional Dynamics of Butternut Canker.
Butternut (Juglans cinerea) is an important component of native biodiversity in eastern North America. Of urgent concern is the survival of butternut, whose populations are declining rapidly, in large part due to an exotic pathogen, Ophiognomonia clavigignenti-juglandacearum, that causes butternut canker. The disease presently occurs throughout the range of butternut in North America, causing branch and stem cankers, dieback, and tree mortality. Despite the existential threat posed by O. clavigignenti-juglandacearum to butternut, a detailed understanding of the factors that drive cross-scale disease patterns is lacking. Therefore, we investigated the association of a range of factors, including tree attributes, topography, and weather, with butternut canker spatial dynamics at different scales using data collected in the province of Quebec, Canada. Trunk canker damage and dieback showed distinct geographic patterns. Bark phenotype was not significantly associated with trunk canker damage. Results suggest that open or dominant trees may show less dieback than intermediate or suppressed trees. Probability of the presence of trunk canker and percent dieback were proportional to the tree diameter at breast height. Temperature was positively associated with disease severity at a 1-km2 scale. Our results provide strong evidence that multiple factors, notably weather, influence butternut canker epidemiology.


Designing high-power, octave spanning entangled photon sources for quantum spectroscopy.
Entangled photon spectroscopy is a nascent field that has important implications for measurement and imaging across chemical, biology, and materials fields. Entangled photon spectroscopy potentially offers improved spatial and temporal-frequency resolutions, increased cross sections for multiphoton and nonlinear measurements, and new abilities in inducing or measuring quantum correlations. A critical step in enabling entangled photon spectroscopies is the creation of high-flux entangled sources that can use conventional detectors as well as provide redundancy for the losses in realistic samples. Here, we report a periodically poled, chirped, lithium tantalate platform that generates entangled photon pairs with ∼10-7 efficiency. For a near watt level diode laser, this results in a near μW-level flux. The single photon per mode limit that is necessary to maintain non-classical photon behavior is still satisfied by distributing this power over up to an octave-spanning bandwidth. The spectral-temporal photon correlations are observed via a Michelson-type interferometer that measures the broadband Hong-Ou-Mandel two-photon interference. A coherence time of 245 fs for a 10 nm bandwidth in the collinear case and a coherence time of 62 fs for a 125 nm bandwidth in the non-collinear case are measured using a CW pump laser and, essentially, collecting the full photon cone. We outline in detail the numerical methods used for designing and tailoring the entangled photons source, such as changing center wavelength or bandwidth, with the ultimate aim of increasing the availability of high-flux UV-Vis entangled photon sources in the optical spectroscopy community.


Informing cancer patient based on his type of personality: the arrogant (narcissistic) patient.
The task of informing the cancer patient is considered an arduous one as it typically involves breaking bad news to the patient. It appears that the adoption of an empathic approach is vital within a therapeutic relationship. This applies to every character or personality type, perhaps more so to the arrogant patient with a feeling of superiority. The question "Is it possible to determine who should be told what, when and how" basically implies the adoption of an empathic approach and the tailoring of information to each cancer patient. The use of character traits contributes to managing the physically ill patient in the best possible way. Therefore, follows the question: in what way does a character or personality type affect cancer patient informing? The aim of this article was to describe the arrogant (narcissistic) character or type of personality in an analytic way so that any therapist can make a diagnosis and tailor the information strategy to the patient's needs. As method of research was used the qualitative method research through groups with doctors and nurses, while research within groups lasted for 5 years. The degree of informing the arrogant personality in the range "minimal - small - medium - large - very large" is: The degree of denial varies between "large" and "very large" while the degree of informing varies between "medium" and "small". Informing the family: The patient objects to a common approach with the family as he is concerned about inflicting a blow to his image.


An empirical model for wind-generated ocean noise.
An empirical model for wind-generated underwater noise is presented that was developed using an extensive dataset of acoustic field recordings and a global wind model. These data encompass more than one hundred years of recording-time and capture high wind events, and were collected both on shallow continental shelves and in open ocean deep-water settings. The model aims to explicitly separate noise generated by wind-related sources from noise produced by anthropogenic sources. Two key wind-related sound-generating mechanisms considered are: surface wave and turbulence interactions, and bubble and bubble cloud oscillations. The model for wind-generated noise shows small frequency dependence (5 dB/decade) at low frequencies (10-100 Hz), and larger frequency dependence (∼15 dB/decade) at higher frequencies (400 Hz-20 kHz). The relationship between noise level and wind speed is linear for low wind speeds (<3.3 m/s) and increases to a higher power law (two or three) at higher wind speeds, suggesting a transition between surface wave/turbulence and bubble source mechanisms. At the highest wind speeds (>15 m/s), noise levels begin to decrease at high frequencies (>10 kHz), likely due to interaction between bubbles and screening of noise radiation in the presence of high-density bubble clouds.


Perfluorinated alkyl substances in snow as an atmospheric tracer for tracking the interactions between westerly winds and the Indian Monsoon over western China.
Snow is an efficient scavenger for the deposition of contaminants. Atmospheric transport and snow deposition jointly control the distribution of pollutants in remote mountain/polar regions. But can the contaminants contained within snow be used to reflect the interactions of air circulation patterns? The physicochemical properties of perfluoroalkyl substances (PFASs) are unique because of their high water solubilities. Taking advantage of this, 15 surface-snow and 3 snow-pit samples were collected across a vast area of western China (spanning 20° of latitude and 25° of longitude), to investigate the concentrations, composition profiles (fingerprints), and deposition fluxes of PFASs. Both a high concentration (3974 pg/L) and deposition flux (4.0 μg/m2/yr) for a total of 16 PFASs were found in the snow at Yulong, the most southern sample site, possibly because of its close proximity to source regions of pollutants in South Asia and high rate of snow deposition. Perfluorobutanoic acid was the most commonly found chemical in snow, but in general the PFAS composition in the snow of western China showed large spatial differences, with long-chain (C > 10) PFASs being relatively dominant in the north and west of the region and short-chain (C < 6) PFASs in the south and east. On the basis of the different compositions of PFASs in the snow of western China and the previously reported features of pollutant sources in Europe and India, we found that PFASs in snow can be used as an atmospheric tracer for tracking the interactions between westerly winds and the Indian Monsoon. The belt along 33°N is a key location where both the Indian Monsoon and westerly winds can arrive/interact; however, the contribution of the monsoon was found to be above 70%, while that of the westerly winds can be lower than 30%. The western part of the 33°N belt was found to be more vulnerable to the Indian Monsoon, and could be grouped into the monsoon domain, while the influence of the westerly winds increased from west to east along the belt. This finding is opposite to previous results, which reported that the western part of the 33°N belt was mainly under the influence of the westerly winds, and for the first time quantifies the relative contribution of westerly winds and the Indian Monsoon to the atmospheric transport of chemicals.


Proximal renal tubular acidosis mediated by mutations in NBCe1-A: unraveling the transporter's structure-functional properties.
NBCe1 belongs to the SLC4 family of base transporting membrane proteins that plays a significant role in renal, extrarenal, and systemic acid-base homeostasis. Recent progress has been made in characterizing the structure-function properties of NBCe1 (encoded by the SLC4A4 gene), and those factors that regulate its function. In the kidney, the NBCe1-A variant that is expressed on the basolateral membrane of proximal tubule is the key transporter responsible for overall transepithelial bicarbonate absorption in this nephron segment. NBCe1 mutations impair transepithelial bicarbonate absorption causing the syndrome of proximal renal tubular acidosis (pRTA). Studies of naturally occurring NBCe1 mutant proteins in heterologous expression systems have been very helpful in elucidation the structure-functional properties of the transporter. NBCe1 mutations are now known to cause pRTA by various mechanisms including the alteration of the transporter function (substrate ion interaction, electrogenicity), abnormal processing to the plasma membrane, and a perturbation in its structural properties. The elucidation of how NBCe1 mutations cause pRTA in addition to the recent studies which have provided further insight into the topology of the transporter have played an important role in uncovering its critically important structural-function properties.