The Effect of Open Access on Scholarly and Societal Metrics of Impact in the ASHA Journals.
This study examined the effect of open access (OA) status on scholarly and societal metrics of impact (citation counts and altmetric scores, respectively) across manuscripts published in the American Speech-Language-Hearing Association (ASHA) Journals. Three thousand four hundred nineteen manuscripts published in four active ASHA Journals were grouped across three access statuses based on their availability to the public: Gold OA, Green OA, and Closed Access. Two linear mixed-effects models tested the effects of OA status on citation counts and altmetric scores of the manuscripts. Both Green OA and Gold OA significantly predicted a 2.70 and 5.21 respective increase in citation counts compared with Closed Access manuscripts (p < .001). Gold OA was estimated to predict a 25.7-point significant increase in altmetric scores (p < .001), but Green OA was only marginally significant (p = .68) in predicting a 1.44 increase in altmetric scores relative to Closed Access manuscripts. Communication sciences and disorders (CSD) research that is fully open receives more online attention and, overall, more scientific attention than research that is paywalled or available through Green OA methods. Additional research is needed to understand secondary variables affecting these and other scholarly and societal metrics of impact across studies in CSD. Ongoing support and incentives to reduce the inequities of OA publishing are critical for continued scientific advancement. Open Science Form: https://doi.org/10.23641/asha.21766919.


Gene and protein expression changes in human trabecular meshwork cells treated with transforming growth factor-beta.
To determine the genomic and proteomic expression changes in human trabecular meshwork cells when they are treated with transforming growth factor (TGF)-beta. Human trabecular meshwork cells from five donors were cultured for 3 days with 1 ng/mL of either TGF-beta1 or -beta2. Changes in gene expression determined with gene microarrays and alterations in protein expression detected by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) were studied in these cells after the incubation. With both TGF-betas, there was a substantial upregulation of genes that were related to secreted proteins or extracellular matrix. This result was consistent with pathologic changes observed in disease and with experiments on perfused trabecular meshwork. Several of the gene changes suggest that other signaling pathways, such as ErbB and Wnt, were altered. Changes in enzyme expression in the prostaglandin pathway indicated that the prostaglandins may have a different cellular profile in the presence of glaucoma. Two genes, osteoblast-specific factor 2 and corneal-derived transcript 6, which are highly expressed in the cells under normal conditions, were substantially upregulated with the TGF-betas. Proteomic analysis indicated that there was increased proteolysis of vimentin with both treatments. Tropomyosin 1alpha was increased in both gene and protein expression, suggesting alterations of the cytoskeleton by the disease. The TGF-beta1 treatment caused more robust changes than those induced by TGF-beta2. Three genes-aldose reductase, thioredoxin reductase 1, and glucose-6-phosphate 1-dehydrogenase-were identified that were downregulated in expression. These genes had decreases in protein expression with TGF-beta1 treatment but had little change in either gene or protein expression with TGF-beta2. Human trabecular meshwork cells can be subjected to increased levels of TGF-beta for several years as a result of glaucoma. The results indicate that changes in extracellular matrix as well as alterations in cytoskeletal proteins occur in these cells as a result of increased TGF-beta. These results are consistent with changes observed in the trabecular meshwork in glaucoma and suggest that at least some of the histologic alterations observed in the meshwork in glaucoma may be the result of increased TGF-betas.


Topical EMLA Cream as a Pretreatment for Facial Lacerations.
Topical anesthetics, such as eutectic mixture of local anesthetics (EMLA) cream, can be applied to reduce pain before minor procedure. This trial evaluated EMLA as pretreatment for facial lacerations and compared pain, discomfort and overall satisfaction. This trial included consecutive emergency department patients ≥16 years of age who presented with simple facial lacerations. At triage, lacerations were allotted to either the routine processing group or EMLA pretreatment group according to date of admission. Initially, the emergency department doctors inspected each laceration, which were dressed with saline-soaked gauze. In the pretreatment group, EMLA cream was applied during wound inspection. The plastic surgeon then completed primary closure following the local injection of an anesthetic. After the procedure, all patients were given a questionnaire assessing pain using the 10-point visual analog scale (VAS) ("no pain" to "worst pain"). All questionnaires were collected by the emergency department nurse before discharge. Fifty patients were included in the routine processing group, and fifty patients were included in the EMLA pretreatment group. Median age was 39.9 years, 66% were male, and the average laceration was 2.67 cm in length. The EMLA pretreatment group reported lower pain scores in comparison with the routine processing group (2.4 vs. 4.5 on VAS, P<0.05), and lower discomfort scores during the procedure (2.0 vs. 3.3, P=0.60). Overall satisfaction was significantly higher in the EMLA pretreatment group (7.8 vs. 6.1, P<0.05). Pretreating facial lacerations with EMLA topical cream aids patients by reducing pain and further enhancing overall satisfaction during laceration treatment.


Mechanisms underlying the QT interval-prolonging effects of sevoflurane and its interactions with other QT-prolonging drugs.
Sevoflurane prolongs ventricular repolarization in patients, but the mechanisms are not fully characterized. The effects of sevoflurane on many cloned human cardiac ion channels have not been studied, and the interactions between sevoflurane and other drugs that prolong cardiac repolarization have not been detailed. The effects of sevoflurane on action potentials and L-type Ca channels in guinea pig myocytes were examined. Sevoflurane's effects on cloned human cardiac K channels and the cloned human cardiac Na channel were studied. The consequences of combining sevoflurane and the class III antiarrhythmic drugs sotalol or dofetilide on action potential duration were also examined. Sevoflurane produced an increase in action potential duration at concentrations of 0.3-1 mm. Contrary to most drugs that delay ventricular repolarization, sevoflurane was without effect on the human ether-a-go-go-related gene cardiac potassium channel but instead produced a reduction in KvLQT1/minK K channel currents and inhibited the Kv4.3 K channel by speeding its apparent rate of inactivation. Sevoflurane had little effect on Na and Ca channel currents at concentrations of 1 mm or less. When the authors coadministered sevoflurane with sotalol or dofetilide, synergistic effects on repolarization were observed, resulting in large increases in action potential duration (up to 66%). Prolonged ventricular repolarization observed with administration of sevoflurane results from inhibition of KvLQT1/minK and Kv4.3 cardiac K channels. Combining sevoflurane with class III antiarrhythmic drugs results in supra-additive effects on action potential duration. The results indicate that sevoflurane, when administered with this class of drug, could result in excessive delays in ventricular repolarization. The results suggest the need for further clinical studies.


808 nm Light-triggered and hyaluronic acid-targeted dual-photosensitizers nanoplatform by fully utilizing Nd(3+)-sensitized upconversion emission with enhanced anti-tumor efficacy.
The current near-infrared (NIR) light-induced photodynamic therapy (PDT) can enhance the tissue penetration depth to trigger photosensitizers (PSs) far from the surface. NIR-mediated PDT is still challenged by overheating effect on normal tissues, limited tumor selectivity and low reactive oxygen species (ROS) yields. Here we construct a dual-agent photosensitizing nanoplatform by combining UV-blue upconversion emitting NaYF4:Yb/Tm@NaYF4:Yb@NaNdF4:Yb@NaYF4 (labeled as UCNPs) multi-shell nanocrystals with titanium dioxide (TiO2, UV-light-excited PS) and hypocrellin A (HA, blue-light-excited PS), which can induce cancer cell apoptosis by 808 nm light-triggered and hyaluronic acid (Hyal)-targeted PDT. In this construction strategy, the crystallized TiO2 shells on the surface of UCNPs can play dual roles as UV-light excited PS and conjugation site for Hyal, and then Hyal is served as targeting-ligand as well as the carrier of HA simultaneously. The step-by-step reactive mode of loading PSs and modifying targeting-ligands is a controllable and ordered design based on the use of one intermediate product as the reaction site for the next component. The Nd(3+)-sensitized UCNPs with quenching reduction layer can efficiently convert 808 nm NIR light to UV-blue emission for simultaneous activation of two PSs with enhanced intracellular ROS generation. Through the in vitro and in vivo experiment results, the dual-photosensitizers nanoplatform presents enhanced anti-tumor efficacy by effective targeting cellular uptake and taking full advantage of upconversion emission, which may make a major step toward next generation of NIR-mediated PDT.


[Angioplasty of the subclavian artery. The technic, early and late results].
Percutaneous transluminal angioplasty (PTA) was performed in 22 patients (13 women and nine men; mean age 57 years [44-74] ) with symptomatic obstruction of the subclavian artery which was due to arteriosclerotic stenosis in 14, occlusion in six patients, radiogenic multiple stenoses in one (after radiotherapy for breast cancer), and stenoses of the left and right subclavian artery in one patient with Takayasu's arteritis. Primary success occurred in 21 (91%). The only complication was a stenosis of the brachial artery after combined brachiofemoral recanalization of a subclavian artery occlusion, but it did not require treatment. No emboli were noted. A good long-term result was achieved in 19 of the 21 primarily successful PTAs, in two instances after repeat PTA. PTA has thus been shown to be a simple, well tolerated interventional treatment of symptomatic subclavian obstruction with a high success rate and low risk of complications. It is to be preferred as a primary procedure to surgical intervention.


Nicotinamide Riboside Improves Cardiac Function and Prolongs Survival After Disruption of the Cardiomyocyte Clock.
The REV-ERB nuclear receptors are key components of the circadian clock. Loss of REV-ERBs in the mouse heart causes dilated cardiomyopathy and premature lethality. This is associated with a marked reduction in NAD+ production, but whether this plays a role in the pathophysiology of this heart failure model is not known. Here, we show that supplementation with the NAD+ precursor NR as a dietary supplement improves heart function and extends the lifespan of female mice lacking cardiac REV-ERBs. Thus, boosting NAD+ levels can improve cardiac function in a setting of heart failure caused by disruption of circadian clock factors, providing new insights into the links between the circadian clock, energy metabolism, and cardiac function.


Assessing relative COVID-19 mortality during the second wave: a prospective Swiss population-based study.
During the first COVID-19 wave in Switzerland, relative mortality was at least eight times higher compared with the uninfected general population. We aimed to assess sex-specific and age-specific relative mortality associated with a SARS-CoV-2 diagnosis during the second wave. Prospective population-based study. Individuals testing positive for SARS-CoV-2 after the start of the second wave on 1 October 2020 were followed up until death or administrative censoring on 31 December 2020. 5 179 740 inhabitants of Switzerland in fall 2018 aged 35-95 years (without COVID-19) and 257 288 persons tested positive for SARS-CoV-2 by PCR or antigen testing during the second wave. The planned outcome measure was time to death from any cause, measured from the date of a SARS-CoV-2 diagnosis or 1 October in the general population. Information on confirmed SARS-CoV-2 diagnoses and deaths was matched by calendar time with the all-cause mortality of the general Swiss population of 2018. Proportional hazards models were used to estimate sex-specific and age-specific mortality rates and probabilities of death within 60 days. The risk of death for individuals tested positive for SARS-CoV-2 in the second wave in Switzerland increased at least sixfold compared with the general population. HRs, reflecting the risk attributable to a SARS-CoV-2 infection, were higher for men (1.40, 95% CI 1.29 to 1.52) and increased for each additional year of age (1.01, 95% CI 1.01 to 1.02). COVID-19 mortality was reduced by at least 20% compared with the first wave in spring 2020. General mortality patterns, increased for men and older persons, were similar in spring and in fall. Absolute and relative COVID-19 mortality was smaller in fall. The protocol for this study was registered on 3 December 2020 at https://osf.io/gbd6r.


Optimizing the productivity and placement of NPs and PAs in outpatient primary care sites.
Organizational leaders must continually assess the productivity, turnover, and vacancies of physician assistants (PAs) and NPs. Optimizing the feasibility, effect, strategic placement, and monitoring increases patient access, improves wait times and affordability, and increases revenue. This quality improvement project sought to develop a systematic, data-driven approach to optimize productivity and placement of NPs and PAs in outpatient primary care sites. Results from this project are reported using the Revised Standards for Quality Improvement Reporting Excellence (SQUIRE) framework. Postformation of a quality improvement team, a gap analysis, and action plans were developed and implemented. Priority areas requiring action included the development of an integrated position justification algorithm and tracking form addressing NP and PA placement, establishing consistent patient contact hours, setting workload expectations, and consistently communicating these via an organization-specific situation, background, assessment, and recommendation communication tool. Healthcare leaders should leverage the talents of NPs and PAs meeting organizational benchmarks and goals as well as the needs of patients. NP and PA leaders should focus on benchmarking performance and analyzing barriers to optimization. These efforts are most beneficial when multidisciplinary in nature.


Developmental changes in the tubular capacity for phosphate reabsorption in the rat.
The need for young, immature animals to maintain positive phosphate balance for growth is well known. However, whether this process involves changes in the intrinsic capacity of the kidney to reabsorb phosphate is not clear. In the present study, the maximum capacity of phosphate reabsorption [Max RPi/glomerular filtration rate (GFR)] was measured in four groups of rats at different stages of development, from weanling to adulthood (3-4, 5-6, 10-14, and 52 wk of age). Clearance experiments were performed in acutely thyroparathyroidectomized (TPTX) rats in the presence and absence of fixed levels of parathyroid hormone (synthetic PTH-(1-34), 1 U.kg-1.min-1). Max RPi/GFR was determined with progressive infusions of phosphate (0-6 mumol Pi/min) that raised the filtered load of phosphate. Max RPi/GFR in TPTX 3- to 4- and 5- to 6-wk-old rats (5.55 +/- 0.36 and 4.28 +/- 0.18 mumol/ml, respectively) was significantly greater than in the corresponding 52-wk-old rats (3.51 +/- 0.13 mumol/ml, P less than 0.05). PTH decreased the Max RPi/GFR in all age groups. However, the developmental pattern was maintained, with the highest levels present in the youngest rats (2.79 +/- 0.25 mumol/ml, P less than 0.05) compared with the other age groups (1.92 +/- 0.23, 1.35 +/- 0.11, and 1.15 +/- 0.13 mumol/ml for 5- to 6-, 10- to 14-, and 52-wk-old rats, respectively). These results demonstrate that the tubular capacity for phosphate reabsorption per milliliter GFR is enhanced in immature rats and progressively decreases with age. This PTH-independent adaptation in young rats may contribute to the renal retention of phosphate during growth.


Evaluation of delayed treatment of focal cerebral ischemia with three selective kappa-opioid agonists in cats.
The purpose of this study was to determine the therapeutic efficacy of three kappa-opioid agonists used for delayed treatment of experimental focal cerebral ischemia. Forty halothane-anesthetized cats underwent permanent occlusion of the right intracranial internal carotid, middle cerebral, and anterior cerebral arteries via a transorbital, microsurgical approach. Six hours after occlusion, animals received a blinded bolus injection, and a subcutaneous osmotic pump was implanted to provide continuous release for 7 days. The injection and pump contained either saline or one of three kappa-agonists: dynorphin (1-13), U-50,488, or DuP E3800. Survival, neurological function, tissue damage, and brain weight were assessed. As a group, kappa-agonist-treated animals had higher survival (P < .02), less tissue damage (P < .02), and lower brain weight (P < .05) than saline controls. U-50,488 more effectively improved survival (P < .03) than dynorphin (P < .07) or E3800 (P < .07). Each of the three kappa compounds improved tissue damage (dynorphin, P < .02; U-50,488, P < .05; E3800, P < .05). Greater improvement in neurological function was seen after treatment with dynorphin (P < .05) than with U-50,488 (P < .6) or E3800 (P < .7). The only significant reduction in brain weight was seen after dynorphin treatment (P < .01). Compounds that act at the kappa subclass of opiate receptors are effective in increasing survival, improving neurological function, and decreasing tissue damage and edema in a cat model of focal cerebral ischemia. The current study provides support for the benefits of treatment of acute cerebrovascular ischemia with kappa-opioid agonists. The agents may prove to be of superior clinical utility because of efficacy even when administered 6 hours after the onset of stroke.


An inframe perforin gene deletion in familial hemophagocytic lymphohistiocytosis is associated with perforin expression.
Familial hemophagocytic lymphohistiocytosis is an autosomal recessive disease of early childhood manifested by hypercytokinemia and organ infiltration of macrophages and activated lymphocytes, and it is characterized by a fulminant clinical course. The molecular mechanism underlying this disease appears to be a deregulation of apoptosis of activated T cells and macrophages. Approximately 20-40% of patients with familial hemophagocytic lymphohistiocytosis reported worldwide had a perforin gene mutation. We report herein a novel perforin variant in the homozygous state in an Omani boy who was diagnosed 44 days after birth. Sequence analysis of the perforin gene coding region revealed a 12-base pair deletion (codon 284-287) resulting in the deletion of four amino acids in the membrane attack complex domain of the protein. This deletion maintains the reading frame of the perforin mRNA. Both parents were heterozygotes for this molecular defect. Flow-cytometric analysis revealed intracellular perforin expression at the lower end of the normal range in the cytotoxic T cells (CD3+/CD8+) and (CD3+/CD56+) and in around 50% of the natural killer cells (CD3-/CD56+). This is an additional example of a perforin variant which is associated with a significant level of cellular perforin expression and thus confirms that drastic reduction in its expression is not a constant feature in familial hemophagocytic lymphohistiocytosis type 2.


Spine and axial skeleton injuries in the National Football League.
The majority of previous literature focusing on spinal injuries in American football players is centered around catastrophic injuries; however, this may underestimate the true number of these injuries in this athletic cohort. The goals of this study were to (1) report the incidence of spinal and axial skeleton injuries, both minor and severe, in the National Football League (NFL) over an 11-year period; (2) determine the incidence of spinal injury by injury type, anatomic location, player position, mechanism of injury, and type of exposure (practice vs game); and (3) determine the average number of practices and days missed because of injury for each injury type. Descriptive epidemiological study. All documented injuries to the cervical, thoracic, and lumbar spine; pelvis; ribs; and spinal cord were retrospectively analyzed using the NFL's injury surveillance database over a period of 11 seasons from 2000 through 2010. The data were analyzed by the number of injuries per athlete-exposure, the anatomic location and type of injury, player position, mechanism of injury, and number of days missed per injury. A total of 2208 injuries occurred to the spine or axial skeleton over an 11-season interval in the NFL, with a mean loss of 25.7 days per injury. This represented 7% of the total injuries during this time period. Of these 2208 injuries, 987 (44.7%) occurred in the cervical spine. Time missed from play was greatest for thoracic disc herniations (189 days/injury). Other injuries that had a mean time missed greater than 30 days included (in descending order) cervical fracture (120 days/injury), cervical disc degeneration/herniation (85 days/injury), spinal cord injury (77 days/injury), lumbar disc degeneration/herniation (52 days/injury), thoracic fracture (34 days/injury), and thoracic nerve injury (30 days/injury). Offensive linemen were the most likely to suffer a spinal injury, followed by defensive backs, defensive linemen, and linebackers. Blocking and tackling were the 2 most frequent injury mechanisms reported. Spinal and axial skeleton injuries occur frequently in the NFL and can result in significant time missed from practices and games. Tackling and blocking result in the greatest number of injuries, and players performing these activities are the most likely to sustain a spinal injury. The results of this study may be used as an impetus to formulate strategies to prevent spinal injuries in American football players.


In Situ Formation of Co9S8 Nanoclusters in Sulfur-Doped Carbon Foam as a Sustainable and High-Rate Sodium-Ion Anode.
Transition-metal sulfides hold great promise as anode materials for sodium-ion batteries due to the high theoretical capacity and excellent redox reversibility based on multielectron conversion reactions. In this work, an elaborate composite, cobalt sulfide nanoclusters embedded in honeycomb-like sulfur-doped carbon foam (Co9S8@S-CF), is prepared via a facile sulfur-assisting calcination strategy, which tactfully induces the co-occurrence of in situ pore-forming, sulfidation, sulfur doping, and carbonization. Notably, sulfur-doped carbon foam (S-CF) possesses abundant voids, which are subject to construction of three-dimensional ionic/electronic pathways, leading to high sodium-ion accessibility and ultrafast sodium-ion/electron transportation toward Co9S8 nanoclusters. When worked as an anode in sodium-ion batteries, it delivers a remarkable capacity of 373 mA h g-1 over 1000 cycles at 0.25 C, achieving superior capacity retention of 80%. Furthermore, this anode could achieve unprecedented rate capability with a reversible capacity of 180 mA h g-1 at 50 C (20 A g-1), which significantly precedes those reported previously.


Single photon ionization time-of-flight mass spectrometry with a pulsed electron beam pumped excimer VUV lamp for on-line gas analysis: setup and first results on cigarette smoke and human breath.
Single-photon ionization (SPI) using vacuum ultraviolet (VUV) light produced by an electron beam pumped rare gas excimer source has been coupled to a compact and mobile time-of-flight mass spectrometer (TOFMS). The novel device enables real-time on-line monitoring of organic trace substances in complex gaseous matrixes down to the ppb range. The pulsed VUV radiation of the light source is employed for SPI in the ion source of the TOFMS. Ion extraction is also carried out in a pulsed mode with a short time delay with respect to ionization. The experimental setup of the interface VUV light source/time-of-flight mass spectrometer is described, and the novel SPI-TOFMS system is characterized by means of standard calibration gases. Limits of detection down to 50 ppb for aliphatic and aromatic hydrocarbons were achieved. First on-line applications comprised real-time measurements of aromatic and aliphatic trace compounds in mainstream cigarette smoke, which represents a highly dynamic fluctuating gaseous matrix. Time resolution was sufficient to monitor the smoking process on a puff-by-puff resolved basis. Furthermore, human breath analysis has been carried out to detect differences in the breath of a smoker and a nonsmoker, respectively. Several well-known biomarkers for smoke could be identified in the smoker's breath. The possibility for even shorter measurement times while maintaining the achieved sensitivity makes this new device a promising tool for on-line analysis of organic trace compounds in process gases or biological systems.


Use of pharmacogenetic data to guide individualized opioid prescribing after surgery.
Despite the current strategies aimed at avoiding opioid overprescription by implementing institutional guidelines, the use of opioids after surgical procedures remains highly variable. It is well known that opioids are activated by the cytochrome p450 CYP2D6 enzyme to exert pharmacologic effect. Individual variation in CYP2D6 activity affects drug metabolism, and genotyping can be performed to predict an individual's ability to metabolize CYP2D6 substrates. We postulate that the pharmacogenomic identification of patients with different opioid metabolism capacity may allow for the individualization of postsurgical opioid prescription. This study was generated by the unison of data from 2 prior initiatives taking place at our Institution. In the first study, patients undergoing 1 of 25 elective surgical procedures were prospectively identified as part of a quality initiative and surveyed by phone 21 to 35 days after hospital discharge to complete a 29-question survey regarding opioid utilization and pain experience. Additional chart abstraction was conducted to obtain prescribing data and pain scores during the hospitalization. The second study was the Mayo Clinic Right Drug, Right Dose, Right Time study protocol, in which 5 pharmacogenes, including CYP2D6, were genotyped for 1,000 Mayo Clinic Biobank participants. The goal of this study was to implement preemptive pharmacogenomics in an academic health care setting and to generate data for further pharmacogenomic research. Patients were classified by their predicted CYP2D6 activity based on their CYP2D6 genotype. Of the 2,486 patients with prospective opioid utilization data, 21 had pharmacogenetic data available and were included in the analysis. These patients were classified according to their activity as opioid metabolizers, with 10 patients (48%) classified as intermediate, 4 patients (19%) as intermediate to normal, and 7 patients (33%) as normal or extensive. Compared with the intermediate to normal and intermediate phenotypes, normal or extensive patients had the highest percentages of preoperative opioid naivety and recorded pain scores throughout the surgical experience. The percentage of unused opioids for intermediate, intermediate to normal, and normal or extensive categories was 79%, 63%, and 46%, respectively. Moreover, of the 14 patients declaring the highest level of satisfaction for their pain control after discharge, 60% belonged to intermediate, 100% to intermediate to normal, and 57% to the normal or extensive group. This study outlines a possible correlation between genetically controlled metabolism and opioid requirements after surgery. In this setting, an increased CYP2D6 enzymatic activity was associated to a greater opioid consumption, lesser amount of unused opioids, and a lower satisfaction level from opioid prescription.


Ultra-portable field transfer radiometer for vicarious calibration of earth imaging sensors.
A small portable transfer radiometer has been developed as part of an effort to ensure the quality of upwelling radiance from test sites used for vicarious calibration in the solar reflective. The test sites are used to predict top-of-atmosphere reflectance relying on ground-based measurements of the atmosphere and surface. The portable transfer radiometer is designed for one-person operation for on-site field calibration of instrumentation used to determine ground-leaving radiance. The current work describes the detector- and source-based radiometric calibration of the transfer radiometer highlighting the expected accuracy and SI-traceability. The results indicate differences between the detector-based and source-based results greater than the combined uncertainties of the approaches. Results from recent field deployments of the transfer radiometer using a solar radiation based calibration agree with the source-based laboratory calibration within the combined uncertainties of the methods. The detector-based results show a significant difference to the solar-based calibration. The source-based calibration is used as the basis for a radiance-based calibration of the Landsat-8 Operational Land Imager that agrees with the OLI calibration to within the uncertainties of the methods.


The irregular xylem9 mutant is deficient in xylan xylosyltransferase activity.
Xylan is the second most abundant polysaccharide in dicot wood, and thus elucidation of the xylan biosynthetic pathway is required to understand the mechanisms controlling wood formation. Genetic and chemical studies in Arabidopsis have implicated three genes, FRAGILE FIBER8 (FRA8), IRREGULAR XYLEM8 (IRX8) and IRREGULAR XYLEM9 (IRX9), in the biosynthesis of glucuronoxylan (GX), but the biochemical functions of the encoded proteins are not known. In this study, we determined the effect of the fra8, irx8 and irx9 mutations on the activities of xylan xylosyltransferase (XylT) and glucuronyltransferase (GlcAT). We show that microsomes isolated from the stems of wild-type Arabidopsis exhibit XylT and GlcAT activities in the presence of exogenous 1,4-linked beta-d-xylooligomers. Xylooligomers ranging in size from two to six can be used as acceptors by XylT to form xylooligosaccharides with up to 12 xylosyl residues. We provide evidence that the irx9 mutation results in a substantial reduction in XylT activity but has no discernible effect on GlcAT activity. In contrast, neither XylT nor GlcAT activity is affected by fra8 and irx8 mutations. Our results provide biochemical evidence that the irx9 mutation results in a deficiency in xylan XylT activity, thus leading to a defect in the elongation of the xylan backbone.


Stress fractures of the lower limbs in runners.
Stress fractures are a common sports injury and running can cause fractures in most bones from the metatarsals to the pubic rami. Pain after an increase in or modification to a running programme is the initial symptom; there will be point tenderness over bone. Rest from running for six to 10 weeks is necessary but alternative exercise must be prescribed for those 'addicted' to running.


Knockdown of aberrantly upregulated aryl hydrocarbon receptor reduces tumor growth and metastasis of MDA-MB-231 human breast cancer cell line.
The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that belongs to the basic-helix-loop-helix (bHLH)-Per-ARNT-Sim (PAS) superfamily of transcription factors, mediates toxic response induced by environmental chemicals such as polycyclic aromatic hydrocarbons (PAH). AhR is expressed at high levels in several human breast carcinoma cell lines in direct correlation with the degree of their malignancy. Recent studies suggest a possible role for AhR in cancer independent of PAH. Therefore, we established stable AhR knockdown cells of the human breast cancer cell line MDA-MB-231 and analyzed their tumorigenic properties in in vitro and in vivo model systems. In addition we analyzed their response to radiation and chemotherapeutic treatment. AhR knockdown attenuated these cells tumorigenic properties in vitro including proliferation, anchorage independent growth, migration and apoptosis and reduced orthotopic xenograft tumor growth and lung metastasis in vivo. Notably, we observed that AhR knockdown enhanced radiation-induced apoptosis as well as significantly decreased cell clonogenic survival. Furthermore, AhR knockdown in MDA-MB-231 cells sensitized them to paclitaxel treatment, evident by a decrease in the required cytotoxic dose. Subsequent analysis revealed AhR knockdown significantly reduced phosphorylation of AKT, which impacts cell proliferation and survival. Apoptosis-focused gene expression analyses revealed an altered expression of genes regulating apoptosis in MDA-MB-231 cells. Collectively, our data identify AhR as a potential novel therapeutic target in the treatment of metastatic breast cancer.


Early 24-hour blood pressure response to Roux-en-Y gastric bypass in obese patients.
Recently, it has been proposed, that the blood pressure (BP) lowering effect of gastric bypass surgery not only is explained by the obtained weight loss, but that the anatomical rearrangement of the gut after 'malabsorptive' surgical techniques, such as the laparoscopic Roux-en-Y gastric bypass (LRYGB), may affect BP through a change in a putative 'entero-renal' axis. If so one could anticipate a reduction in BP even before a noticeable weight loss was obtained. The purpose of the present study was to investigate the very early BP response to LRYGB surgery. Ten severely obese hypertensive (mean BMI 40.8 kg/m2) and 10 severely obese normotensive (mean BMI 41.7 kg/m2) patients underwent 24-h ambulatory blood pressure measurements (24 h ABPMs) before LRYGB and again day 1 and day 10 after LRYGB. No change in 24 h BP was observed day 1 after LRYGB. Day 10 after surgery both hypertensive and normotensive patients demonstrated a significant 12.6 mmHg and 9.5 reduction in systolic BP (SBP), respectively. Mean arterial pressure (MAP) decreased by 8.3 and 5.4 mmHg. At day 10 postoperatively, a weight loss of 7.9 kg in the hypertensive patients and 7.0 kg in the normotensive patients was observed. The reduction in BP after LRYGB takes place before any substantial weight loss has occurred. The reason for this remains speculative, but obese hypertensive patients may clearly benefit from the operation even if the goal of achieving 'normoweight' is not obtained.


Controversies in spine research: Organ culture versus in vivo models for studies of the intervertebral disc.
Intervertebral disc degeneration is a common cause of low back pain, the leading cause of disability worldwide. Appropriate preclinical models for intervertebral disc research are essential to achieving a better understanding of underlying pathophysiology and for the development, evaluation, and translation of more effective treatments. To this end, in vivo animal and ex vivo organ culture models are both widely used by spine researchers; however, the relative strengths and weaknesses of these two approaches are a source of ongoing controversy. In this article, members from the Spine and Preclinical Models Sections of the Orthopedic Research Society, including experts in both basic and translational spine research, present contrasting arguments in support of in vivo animal models versus ex vivo organ culture models for studies of the disc, supported by a comprehensive review of the relevant literature. The objective is to provide a deeper understanding of the respective advantages and limitations of these approaches, and advance the field toward a consensus with respect to appropriate model selection and implementation. We conclude that complementary use of several model types and leveraging the unique advantages of each is likely to result in the highest impact research in most instances.


IMPIPS: the immune protection-inducing protein structure concept in the search for steric-electron and topochemical principles for complete fully-protective chemically synthesised vaccine development.
Determining immune protection-inducing protein structures (IMPIPS) involves defining the stereo-electron and topochemical characteristics which are essential in MHC-p-TCR complex formation. Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures. They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR). Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response. Immunological assays in Aotus monkeys involving IMPIPS mixtures led to promising results; taken together with the aforementioned physicochemical principles, non-interfering, long-lasting, protection-inducing, multi-epitope, multistage, minimal subunit-based chemically-synthesised peptides can be designed against diseases scourging humankind.


β-FeOOH: a new anode for potassium-ion batteries.
Potassium-ion batteries (PIBs) hold great potential in large-scale energy storage systems. Here, β-FeOOH is employed as an anode for PIBs, exhibiting high capacity and good cycling stability. The study of potassium storage mechanism discloses that β-FeOOH turns into an amorphous structure in the first discharge process, and remains stable in the amorphous state in the subsequent cycles.


Unexpected morphological diversity in ancient dogs compared to modern relatives.
Dogs are among the most variable species today, but little is known about the morphological variability in the early phases of their history. The Neolithic transition to farming may have resulted in an early morphological diversification as a result of changes in the anthropic environment or intentional selection on specific morphologies. Here, we describe the variability and modularity in mandible form by comparing 525 dog mandibles from European archaeological sites ranging from 8100 to 3000 cal. BC to a reference sample of modern dogs, wolves, and dingoes. We use three-dimensional geometric morphometrics to quantify the form of complete and fragmented mandibles. We demonstrate that an important morphological variability already existed before the Bronze Age in Europe, yet the largest, smallest, most brachycephalic or dolichocephalic extant dogs have no equivalent in the archaeological sample, resulting in a lower variation compared to modern relatives. The covariation between the anterior and posterior parts of the mandible is lower in archaeological dogs, suggesting a low degree of intentional human selection in early periods. The mandible of modern and ancient dogs differs in functionally important areas, possibly reflecting differences in diet, competition, or the implication of ancient dogs in hunting or defence.


The unrecognized occupational relevance of the interaction between engineered nanomaterials and the gastro-intestinal tract: a consensus paper from a multidisciplinary working group.
There is a fundamental gap of knowledge on the health effects caused by the interaction of engineered nanomaterials (ENM) with the gastro-intestinal tract (GIT). This is partly due to the incomplete knowledge of the complex physical and chemical transformations that ENM undergo in the GIT, and partly to the widespread belief that GIT health effects of ENM are much less relevant than pulmonary effects. However, recent experimental findings, considering the role of new players in gut physiology (e.g. the microbiota), shed light on several outcomes of the interaction ENM/GIT. Along with this new information, there is growing direct and indirect evidence that not only ingested ENM, but also inhaled ENM may impact on the GIT. This fact, which may have relevant implications in occupational setting, has never been taken into consideration. This review paper summarizes the opinions and findings of a multidisciplinary team of experts, focusing on two main aspects of the issue: 1) ENM interactions within the GIT and their possible consequences, and 2) relevance of gastro-intestinal effects of inhaled ENMs. Under point 1, we analyzed how luminal gut-constituents, including mucus, may influence the adherence of ENM to cell surfaces in a size-dependent manner, and how intestinal permeability may be affected by different physico-chemical characteristics of ENM. Cytotoxic, oxidative, genotoxic and inflammatory effects on different GIT cells, as well as effects on microbiota, are also discussed. Concerning point 2, recent studies highlight the relevance of gastro-intestinal handling of inhaled ENM, showing significant excretion with feces of inhaled ENM and supporting the hypothesis that GIT should be considered an important target of extrapulmonary effects of inhaled ENM. In spite of recent insights on the relevance of the GIT as a target for toxic effects of nanoparticles, there is still a major gap in knowledge regarding the impact of the direct versus indirect oral exposure. This fact probably applies also to larger particles and dictates careful consideration in workers, who carry the highest risk of exposure to particulate matter.


Mapping the literature of case management nursing.
Nursing case management provides a continuum of health care services for defined groups of patients. Its literature is multidisciplinary, emphasizing clinical specialties, case management methodology, and the health care system. This study is part of a project to map the literature of nursing, sponsored by the Nursing and Allied Health Resources Section of the Medical Library Association. The study identifies core journals cited in case management literature and indexing services that access those journals. Three source journals were identified based on established criteria, and cited references from each article published from 1997 to 1999 were analyzed. Nearly two-thirds of the cited references were from journals; others were from books, monographs, reports, government documents, and the Internet. Cited journal references were ranked in descending order, and Bradford's Law of Scattering was applied. The many journals constituting the top two zones reflect the diversity of this field. Zone 1 included journals from nursing administration, case management, general medicine, medical specialties, and social work. Two databases, PubMed/MEDLINE and OCLC ArticleFirst, provided the best indexing coverage. Collections that support case management require a relatively small group of core journals. Students and health care professionals will need to search across disciplines to identify appropriate literature.


Functional and morphological studies of mitochondria exposed to undecagold clusters: biologic surfaces labeling with gold clusters.
This study reports morphological and functional alterations observed in respiring isolated mitochondria when they are exposed to nonpenetrating, positive electrostatically charged synthetic undecagold clusters. Modification of the undecagold clusters positive charges change or prevent the functional effects and the binding to the outside surface of the mitochondria. The mitochondrial functional alterations are dependent on the oxidative phosphorylation capacity of the isolated organelles. The results of these experiments indicate that artificial undecagold may be useful to explore the molecular mechanisms of biological energy transducers which require electric charges separation, ionic fluxes, and electric surface properties.


When courts review medical appropriateness.
The authors examined how the courts have responded to public and private insurers' use of medical appropriateness criteria to establish coverage and payment policies. A structured review of all federal and state court health insurance cases decided between 1960 and June 1994 that involved a dispute involving medical appropriateness was performed. A total of 3,215 published court decisions were analyzed, of which 203 met the criteria of relevance and 124 explicitly mentioned medical appropriateness criteria. The main outcome variable was whether the court ordered the insurer to provide coverage. In 185 cases, a definitive decision was rendered, and the insurer was required to pay in 57% of the decisions. Whether the insurer relied on an assessment or not, whether the assessment process was formal or informal, and who conducted the assessment did not appear to influence courts' decisions, nor did the specificity of the coverage exclusion. Significant predictors of courts ordering coverage were court jurisdiction, contract language assigning discretion to the insurer, severity of patient's condition, and whether the treatment appeared to work for the particular patient. For practice guidelines to be accepted by the courts, it is more important to focus on how insurance contracts are written than on how medical assessments are performed.


Effect of Methanolic Extract of Dandelion Roots on Cancer Cell Lines and AMP-Activated Protein Kinase Pathway.
Ethnomedicinal knowledge of plant-derived bioactives could help us in discovering new therapeutic compounds of great potential. Certainly, dandelion has been used in traditional ethno-medicinal systems (i.e., Chinese, Arabian, Indian, and Native American) to treat different types of cancer. Though, dandelion is highly vigorous, but the potential mode of action is still unclear. In the current study, the antiproliferative activity of methanolic extracts of dandelion root (MEDr) on cell viability of HepG2, MCF7, HCT116, and normal Hs27 was investigated. It was observed that MEDr (500 μg/mL) drastically decreased the growth of HepG2 cell line, while the effect on MCF7 and HCT116 cell lines was less pronounced and no effect has been observed in Hs27 cell lines. The MEDr also enhanced the phosphorylation level of AMPK of HepG2 cells, which considered crucial in cancer treatment and other metabolic diseases. The AMPK activation by MEDr noticed in the current study has never been reported previously. The results regarding the number of apoptotic cells (HepG2 cells) were in line with the cell viability test. The current observations clearly demonstrated the potency of MEDr against liver cancer with validation that dandelion could control AMPK and thus cancer in the treated cell lines.


Metabolite Profiling in Withania somnifera Roots Hydroalcoholic Extract Using LC/MS, GC/MS and NMR Spectroscopy.
Ashwagandha (Withania somnifera) is a very well-known herbal medicine and it was well studied for its active metabolites throughout the World. Although, nearly 40 withanolides were isolated from W. somnifera root extract, still there is remaining unidentified metabolites due to very low abundance and geographical variation. Advanced separation technology with online identification by mass and nuclear magnetic resonance (NMR) are nowadays used to find out the new compounds in the crude herbal extract. This article described the metabolite profiling of ashwagandha root hydroalcoholic extract using ultra-performance liquid chromatography coupled with a positive ion electrospray ionization tandem mass spectrometry through gas chromatography mass spectrometry (GC/MS) and NMR spectroscopy. A total of 43 possible withanolides was identified and proposed their structures based on the mass of molecular and fragment ions. GC/MS and NMR analysis indicated the presence of several known withanolides including withaferin A, withanolide D, withanoside IV or VI, withanolide sulfoxide, etc. To the best of our knowledge, dihydrowithanolide D at m/z 473 (tR 7.86 min) and ixocarpalactone A at m/z 505 (tR 8.43 min) were first time identified in the ashwagandha root hydroalcoholic extract. The current study that described the identification of withanolides with summarized literature review might be helpful for designing the experiment to identify of the new chemical constituents in Withania species.


Purification and properties of neutral maltase from human granulocytes.
A procedure for the purification of neutral maltase from human polymorphonuclear leukocytes is described, involving solubilization with Triton X-100, proteolytic attack and three chromatographic steps: DEAE ion exchange, AcA 22 gel filtration and a second DEAE chromatography. The enzyme was obtained with a final specific activity of 30 units/mg of protein, comparable with that of other neutral maltases previously purified. The Mr of the enzyme was 550,000 as determined by gel filtration. SDS/polyacrylamide-gel electrophoresis, under non-denaturing conditions, led to a major band of 500,000 and a minor one of 260,000, both active, suggesting a polymeric or aggregated form of the protein. The catalytic properties of the human granulocytic neutral maltase were investigated. The pH optimum was around 6. The enzyme exhibited a broad range of substrate specificity, hydrolysing di- and oligosaccharides with alpha (1----2), alpha (1----3) and alpha (1----4) glucosidic linkages. The highest activities were observed for alpha (1----4) glucose oligomers of three to five residues. It was also found to hydrolyse polysaccharides such as starch and glycogen. The results of the inhibition studies are interpreted in terms of the existence of a large site including several subsites. The enzyme properties are broadly similar to those observed for other purified neutral alpha-glucosidases, in particular that of human kidney origin.


Isolation of cross-reactive human monoclonal antibodies that prevent binding of human noroviruses to histo-blood group antigens.
In order to identify the repertoire of antibodies generated on natural infection of norovirus (NoV) in humans, and to characterize the human monoclonal antibodies against NoV, three phage-displayed antibody libraries originating from healthy person(s) were screened using purified virus-like particles (VLPs) of strain Narita 104 (r104, genogroup II, genotype 4) or strain Chiba 407 (rCV, genogroup I, genotype 4) as antigens. On screening with r104, 62 clones were isolated. Among these antibodies, two clones, 12A11 and 12B10, showed intra-genogroup cross-reactivity to genotypes 1, 3-7, 12, and 14, and genotypes 1, 4, 6, and 7 of genogroup II, respectively. In addition, antibodies belonging to the same group were isolated from two different libraries. On screening with rCV, five clones were isolated, two of which were cross-reactive. One, CV-2F5, reacted to genotypes 1-4, and 8 of genogroup I, and the other, CV-1A5, showed inter-genogroup cross-reactivity to all the VLPs employed in this study. The blocking activities of the monoclonal antibodies against the interaction of homotypic VLPs (VLPs used in the panning procedure) with histo-blood group antigens were also assessed as an alternative to neutralization assay. Although the blocking activity of 12A11 was partially limited 12B10 prevented the binding of r104 to histo-blood group antigens that had been reported to bind r104. The blocking activity of CV-2F5 against the attachment of rCV to suitable histo-blood group antigens was weak, but the blocking activity of CV-1A5 was well recognized. Thus, 12B10 and CV-1A5 were suggested to be cross-reactive monoclonal antibodies with neutralizing activity.


Comparison of transesophageal and transthoracic echocardiography under moderate sedation for guiding transcatheter aortic valve replacement.
The optimal periprocedural imaging strategy during transcathether aortic valve replacement (TAVR) performed under moderate sedation is debated. Transthoracic echocardiography (TTE) provides suboptimal views due to poorer resolution and patient positioning, whereas use of transesophageal echocardiography (TEE) under moderate sedation is not widely utilized. The aim of our study was to compare the value of TTE in comparison with TEE guidance under moderate sedation during TAVR. The study population included 144 consecutive patients (mean age 83 ± 11 years, 78 (54%) females) who had TAVR under moderate sedation using either a TTE (n = 96) or TEE (n = 48). We compared procedural outcomes using propensity score matching. There were no significant inter-group differences in age, sex, ejection fraction, aortic valve area, pressure gradients, creatinine or type of valve used. The procedural time was significantly shorter in the TEE group (P < 0.001) and associated with a lower need for periprocedural aortograms (7.7 ± 1.9 vs 8.2 ± 1.9, P = 0.022) and a lower occurrence of acute kidney injury (1 vs 11, P = 0.047). The 1:1 propensity score matching also showed a lower procedural time (P = 0.032), number of aortograms (P = 0.014) and a trend toward lower acute kidney injury in the TEE group (P = 0.077). TAVR guidance using TEE is associated with a lower fluoroscopic time, a lower need for additional aortograms and trend in lower occurrence of post-TAVR acute kidney injury.


Genome-Wide Association Study Reveals Marker Trait Associations (MTA) for Waterlogging-Triggered Adventitious Roots and Aerenchyma Formation in Barley.
Waterlogging is an environmental stress, which severely affects barley growth and development. Limited availability of oxygen in the root zone negatively affects the metabolism of the whole plant. Adventitious roots (AR) and root cortical aerenchyma (RCA) formation are the most important adaptive traits that contribute to a plant's ability to survive in waterlogged soil conditions. This study used a genome-wide association (GWAS) approach using 18,132 single nucleotide polymorphisms (SNPs) in a panel of 697 barley genotypes to reveal marker trait associations (MTA) conferring the above adaptive traits. Experiments were conducted over two consecutive years in tanks filled with soil and then validated in field experiments. GWAS analysis was conducted using general linear models (GLM), mixed linear models (MLM), and fixed and random model circulating probability unification models (FarmCPU model), with the FarmCPU showing to be the best suited model. Six and five significant (approximately -log10 (p) ≥ 5.5) MTA were identified for AR and RCA formation under waterlogged conditions, respectively. The highest -log10 (p) MTA for adventitious root and aerenchyma formation were approximately 9 and 8 on chromosome 2H and 4H, respectively. The combination of different MTA showed to be more effective in forming RCA and producing more AR under waterlogging stress. Genes from major facilitator superfamily (MFS) transporter and leucine-rich repeat (LRR) families for AR formation, and ethylene responsive factor (ERF) family genes and potassium transporter family genes for RCA formation were the potential candidate genes involved under waterlogging conditions. Several genotypes, which performed consistently well under different conditions, can be used in breeding programs to develop waterlogging-tolerant varieties.


A Qualitative Study of the Communication Process for Medical Acupuncture in Family Medicine.
As evidence establishes the efficacy of medical acupuncture, more family physicians and family medicine residents may receive medical acupuncture training and need to know how to effectively communicate about the treatment option with patients. By identifying how physicians talk about acupuncture treatment with their patients, we aimed to develop a model for physician training that could enhance their ability to integrate and practice medical acupuncture in conventional clinical settings. To capture the communication process that family physicians engage in when integrating acupuncture treatment into a clinical environment, we sought both physicians' and patients' perspectives. We conducted interviews with 17 family physicians and 15 patients in a US family medicine clinic that has integrated medical acupuncture into its practice. Audio recordings were transcribed and analyzed by two members of the study team in ATLAS.ti, using the constant comparative method. Integrating acupuncture into family medicine entailed a three-phase communication process: (1) introduce acupuncture, (2) explain the medical process, and (3) evaluate treatment outcomes. The emerging three-phase process of communicating acupuncture described here provides an initial model for teaching communication in the context of medical acupuncture. Given the exploratory nature of this initial study and the rarity of acupuncture treatment integrated into family medical settings, this is a first step in building knowledge in this realm of practice. Future research is needed to better understand the experience of patients who do not report notable results of acupuncture and to extend this study into other family medicine settings.


Antioxidant supplementation and risk of incident melanomas: results of a large prospective cohort study.
To examine whether antioxidant supplement use is associated with melanoma risk in light of recently published data from the Supplementation in Vitamins and Mineral Antioxidants (SUVIMAX) study, which reported a 4-fold higher melanoma risk in women randomized to receive a supplement with nutritionally appropriate doses of antioxidants. Population-based prospective study (Vitamins and Lifestyle [VITAL] cohort). Western Washington State. A total of 69 671 men and women who self-reported (1) intake of multivitamins and supplemental antioxidants, including selenium and beta carotene, during the past 10 years and (2) melanoma risk factors on a baseline questionnaire. Main Outcome Measure Incident melanoma identified through linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Cox proportional hazards regression models were used to estimate multivariable relative risks (RRs) and 95% confidence intervals (CIs) for multivitamin, supplemental selenium, and supplemental beta carotene use. After adjusting for melanoma risk factors, we did not detect a significant association between multivitamin use and melanoma risk in women (RR, 1.14; 95% CI, 0.78-1.66) or in men (RR, 1.09; 95% CI, 0.83-1.43). Moreover, we did not observe increased melanoma risk with the use of supplemental beta carotene (RR, 0.87; 95% CI, 0.48-1.56) or selenium (RR, 0.98; 95% CI, 0.69-1.41) at doses comparable with those of the SUVIMAX study. Conclusion Antioxidants taken in nutritional doses do not seem to increase melanoma risk.


Prolactin-immune interactions in carcinogen-induced rat mammary tumors.
Because many mammary tumors are prolactin (PRL) dependent, tumor-bearing animals are immunocompromised, and PRL directly affects the immune system, we examined the endocrine and immune systems of rats initiated with nitrosomethylurea (NMU) to cause mammary tumors. We tested: a) PRL cells in the pituitary; b) pituitary PRL as detected by radioimmunoassay (RIA), Nb2 bioassay, and induction of interleukin-2 receptors on splenocytes; c) induction of IL-2R on lymphocytes in response to a standard PRL; d) CD phenotype of the splenocytes and tumor infiltrating lymphocytes. We found that 80% of all NMU-treated animals developed mammary tumors 10 to 13 weeks post-injection. PRL cell number, size, and granule content were unaffected. When tested by RIA or by the Nb2 bioassay, there appeared to be approximately 50% less PRL secreted (2 weeks post-injection) by cells of the NMU-treated than the vehicle-treated animals. However, when tested by IL-2R assay, PRL cells of NMU-treated animals secreted 50% more activity. Splenocytes from the treated animals, 2-6 weeks post-injection, expressed fewer IL-2R in response to standard PRL. NMU treatment (12 wks post-injection) increased the numbers of T-cytotoxic cells by 49%, had no effect on T-helpers, and increased the number of IL-2R positive splenocytes by 81%. Our interpretation is that NMU treatment interferes with the feedback of lymphokines on the pituitary with a decrease in the form of PRL detected by the RIA and Nb2 assays and an increase in the form which activates splenocytes, and thus changes the composition and function of the immune system.


Liver disease in pregnancy.
Pregnancy is a time of great maternal physiological and metabolic changes. This affects the biochemical and haematological parameters used in the assessment of liver disease, and it is important to appreciate the different reference ranges in pregnancy to facilitate recognition of liver disorders in pregnancy. Due to the increased physiological and metabolic stress of pregnancy, liver disorders that have previously been subclinical may become symptomatic-for example, primary biliary cirrhosis. Gallstone disease is a common problem in women of childbearing age, and pregnancy promotes their formation. The viral hepatidides constitute a huge disease burden worldwide and the pregnant state confers particular concerns for the mother and her baby. In particular, hepatitis E has a predilection for the pregnant population and confers a particularly poor prognosis. In addition certain pregnancy specific disorders-for example, haemolysis, elevated liver enzymes, low platelets syndrome, acute fatty liver of pregnancy, and obstetric cholestasis-affect primarily the liver. It is important to know how to diagnose and manage these conditions and distinguish them from non-pregnancy specific conditions as this will change the timing and management of affected women and their babies, some of whom can be seriously ill. We propose an approach to the investigation and management of the pregnant patient with abnormal liver function tests.


Changes in Specific Substance Involvement Scores among SBIRT recipients in an HIV primary care setting.
Substance use is common among people living with HIV (PLHIV) and is associated with worse outcomes along the HIV care continuum. One potentially effective clinic-based approach to addressing unhealthy substance use is screening, brief intervention, and referral to treatment (SBIRT). We conducted a two-arm randomized trial to examine the effects of a self-administered, computerized SBIRT intervention compared to a clinician-administered SBIRT intervention in an HIV primary clinic. Patients were surveyed before receiving the intervention and again at 1, 3, and 6 months. We administered the WHO Alcohol, Smoking and Substance Involvement Screening Test to determine Specific Substance Involvement Scores (SSIS) and to assign participants to categories of lower, moderate, or high risk to health and other problems for each substance. We collapsed moderate or severe risk responses into a single moderate-high risk category. Based on low rates of participation in the computerized arm, we conducted an "as treated" analysis to examine 6-month changes in mean SSIS among SBIRT intervention participants. For the overall sample (n = 208), baseline mean SSIS were in the moderate risk category for alcohol, tobacco, cannabis, cocaine, amphetamine, sedatives and opioids. Of those enrolled, 134 (64.4%) received the intervention, and 109 (52.4%) completed the 6-month follow up. There was a statistically significant decline in mean SSIS for all substances except tobacco and cannabis among participants who were at moderate-high risk at baseline. We also observed a statistically significant increase in mean SSIS for all substances except amphetamines and sedatives among participants who were at lower risk at baseline. Substance use among patients in this urban, safety-net, HIV primary care clinic was near universal, and moderate risk substance use was common. Among participants who received the SBIRT intervention, mean SSISs decreased among those at moderate-high risk at baseline, but increased among those at lower risk at baseline over the 6-month study period. Additional research should examine the clinical significance of SSIS changes for PLHIV, which SBIRT components drive changes in substance use scores, and what other interventions might support those patients at lower risk to maintain health and engagement along the HIV care continuum. Trial registration ClinicalTrials.gov study NCT01300806.


OCTAL: Optimal Completion of gene trees in polynomial time.
For a combination of reasons (including data generation protocols, approaches to taxon and gene sampling, and gene birth and loss), estimated gene trees are often incomplete, meaning that they do not contain all of the species of interest. As incomplete gene trees can impact downstream analyses, accurate completion of gene trees is desirable. We introduce the Optimal Tree Completion problem, a general optimization problem that involves completing an unrooted binary tree (i.e., adding missing leaves) so as to minimize its distance from a reference tree on a superset of the leaves. We present OCTAL, an algorithm that finds an optimal solution to this problem when the distance between trees is defined using the Robinson-Foulds (RF) distance, and we prove that OCTAL runs in [Formula: see text] time, where n is the total number of species. We report on a simulation study in which gene trees can differ from the species tree due to incomplete lineage sorting, and estimated gene trees are completed using OCTAL with a reference tree based on a species tree estimated from the multi-locus dataset. OCTAL produces completed gene trees that are closer to the true gene trees than an existing heuristic approach in ASTRAL-II, but the accuracy of a completed gene tree computed by OCTAL depends on how topologically similar the reference tree (typically an estimated species tree) is to the true gene tree. OCTAL is a useful technique for adding missing taxa to incomplete gene trees and provides good accuracy under a wide range of model conditions. However, results show that OCTAL's accuracy can be reduced when incomplete lineage sorting is high, as the reference tree can be far from the true gene tree. Hence, this study suggests that OCTAL would benefit from using other types of reference trees instead of species trees when there are large topological distances between true gene trees and species trees.


Pheophytin a and chlorophyll a identified from environmentally friendly cultivation of green pepper enhance interleukin-2 and interferon-γ in Peyer's patches ex vivo.
The oral consumption of capsicum has been reported to increase interleukin (IL)-2 and interferon (IFN)-γ production in Peyer's patches (PP); however, the active components responsible for these effects have not been completely identified. The beneficial biological effects of green peppers cultivated under environmentally friendly farming conditions (ECP), without the use of chemical pesticides, have rarely been compared with those of green peppers cultivated under conventional farming conditions (CCP). Oral administration of ECP extract significantly induced the production of IL-2 and IFN-γ in concanavalin A-treated cells from PP ex vivo; their levels were much higher than those in the CCP extract-treated group. A comparative analysis of the HPLC profiles indicated a 1.7-fold increase of a peak, named EF-1, at 415 nm in the ECP extract. The major component of EF-1 was identified as pheophytin a, which is a chlorophyll a molecule lacking a central Mg(2+) ion, as determined from NMR data. Intake of pheophytin a and chlorophyll a significantly increased IL-2 and IFN-γ production, and the percentage of IL-2- and IFN-γ-producing CD4+ T-cells in PP. Taken together, our data suggest that ECPs produce a higher content of pheophytin a than CCPs, and pheophytin a and chlorophyll a are immune-modulating components in green vegetables.


[Hyperbaric oxygen therapy in sudden deafness].
Based on two independent studies, an attempt is made in this paper to demonstrate the effect of hyperbaric oxygen therapy used as a supportive measure to accompany standard treatment in recent acute loss of hearing and in acute loss of hearing where preoperative treatment has proved unsatisfactory. Whereas hyperbaric oxygen therapy is superior to the standard treatment alone as far as the cochlear perception dysacousis and tinnitus in recent acute loss of hearing are concerned, these results could not be reproduced in existing, preoperatively treated acute loss of hearing. As such, hyperbaric oxygen therapy under the strict supervision of a specialist physician has proved an effective supportive measure in the treatment of recent acute loss of hearing.


[Cancer of the esophagus (I): its epidemiological, clinical and diagnostic assessment according to histological type].
From 1975 to 1991, sixty-eight patients were treated with surgery for esophageal cancer at the Clínica Universitaria de Navarra. This study involves an analysis of epidemiologic and predisposing risk factors in relation with the histologic type of tumor: epidermoid carcinoma vs. adenocarcinoma. The difference in mean age of males (60.5 yrs.) as compared with that of females (48.7 yrs.) was statistically significant (p < 0.05). Likewise, the mean age of patients with epidermoid carcinoma (57.8 yrs.) was significant lower (p < 0.01) as compared with that of those with adenocarcinoma (66.3 yrs.). Smoking and alcoholism were common in the group of patients with epidermoid carcinoma, while Barrett's esophagus and hiatal hernia were frequently seen in patients with adenocarcinoma. Dysphagia was the most frequent symptom both at the start of disease (75%) and with the diagnosis established (96.7%). There was no significant difference in the symptomatology of patients with one type of tumor or the other. The efficacy of ancillary diagnostic procedures such as barium swallow, esophagoscopy, computerized tomography and biopsy were likewise assessed. The most frequent site of tumor was at the middle third, with majority of patients being at clinical stage 1-2 of disease at the time of diagnosis.


Psychometric study of the Portuguese version of the Family Distress Index (FDI).
The current study examined the psychometric properties of the Portuguese version of the Family Distress Index (FDI). The FDI is an 8-item self-report measure that assesses family maladaptation, providing an index of family outcomes within the resiliency model of family stress, adjustment, and adaptation. Participants were 459 adults, who completed measures of family distress (FDI) and family functioning (Systemic Clinical Outcome Routine Evaluation; SCORE-15). Exploratory and confirmatory factor analyses supported a unidimensional factorial structure. Results also indicated that the FDI has good internal consistency and temporal stability. The positive and significant correlation between FDI and SCORE-15' scores demonstrated its convergent validity. Through receiver operating characteristic (ROC) analysis, we determined a cut-off score of 12 for identifying probable family distress. In sum, the Portuguese version of the FDI is a valid and reliable instrument, which can foster the development of future empirical studies focused on family adaptation in diverse contexts of adversity, namely in health care settings. (PsycINFO Database Record


Impact of spectral phase mismatch on femtosecond coherent beam combining systems.
We experimentally investigate the impact of spectral phase mismatch on the coherent beam combining of two femtosecond fiber chirped-pulse amplifiers. By measuring the differential spectral phase, both linear and nonlinear contributions are identified. An accumulated nonlinear phase as high as 6 rad has been measured, for which a combination efficiency of 91% can be obtained by symmetrizing the pump and injection powers. This also allows us to quantitatively separate the spatial and temporal contributions of the nonperfect combining efficiency.


Unlocking interpretation in near infrared multivariate calibrations by orthogonal partial least squares.
Near infrared spectroscopy (NIR) was developed primarily for applications such as the quantitative determination of nutrients in the agricultural and food industries. Examples include the determination of water, protein, and fat within complex samples such as grain and milk. Because of its useful properties, NIR analysis has spread to other areas such as chemistry and pharmaceutical production. NIR spectra consist of infrared overtones and combinations thereof, making interpretation of the results complicated. It can be very difficult to assign peaks to known constituents in the sample. Thus, multivariate analysis (MVA) has been crucial in translating spectral data into information, mainly for predictive purposes. Orthogonal partial least squares (OPLS), a new MVA method, has prediction and modeling properties similar to those of other MVA techniques, e.g., partial least squares (PLS), a method with a long history of use for the analysis of NIR data. OPLS provides an intrinsic algorithmic improvement for the interpretation of NIR data. In this report, four sets of NIR data were analyzed to demonstrate the improved interpretation provided by OPLS. The first two sets included simulated data to demonstrate the overall principles; the third set comprised a statistically replicated design of experiments (DoE), to demonstrate how instrumental difference could be accurately visualized and correctly attributed to Wood's anomaly phenomena; the fourth set was chosen to challenge the MVA by using data relating to powder mixing, a crucial step in the pharmaceutical industry prior to tabletting. Improved interpretation by OPLS was demonstrated for all four examples, as compared to alternative MVA approaches. It is expected that OPLS will be used mostly in applications where improved interpretation is crucial; one such area is process analytical technology (PAT). PAT involves fewer independent samples, i.e., batches, than would be associated with agricultural applications; in addition, the Food and Drug Administration (FDA) demands "process understanding" in PAT. Both these issues make OPLS the ideal tool for a multitude of NIR calibrations. In conclusion, OPLS leads to better interpretation of spectrometry data (e.g., NIR) and improved understanding facilitates cross-scientific communication. Such improved knowledge will decrease risk, with respect to both accuracy and precision, when using NIR for PAT applications.


Evaluating depression with multimodal wristband-type wearable device: screening and assessing patient severity utilizing machine-learning.
We aimed to develop a machine learning algorithm to screen for depression and assess severity based on data from wearable devices. We used a wearable device that calculates steps, energy expenditure, body movement, sleep time, heart rate, skin temperature, and ultraviolet light exposure. Depressed patients and healthy volunteers wore the device continuously for the study period. The modalities were compared hourly between patients and healthy volunteers. XGBoost was used to build machine learning models and 10-fold cross-validation was applied for the validation. Forty-five depressed patients and 41 healthy controls participated, creating a combined 5,250 days' worth of data. Heart rate, steps, and sleep were significantly different between patients and healthy volunteers in some comparisons. Similar differences were also observed longitudinally when patients' symptoms improved. Based on seven days' data, the model identified symptomatic patients with 0.76 accuracy and predicted Hamilton Depression Rating Scale-17 scores with a 0.61 correlation coefficient. Skin temperature, sleep time-related features, and the correlation of those modalities were the most significant features in machine learning. The small number of subjects who participated in this study may have weakened the statistical significance of the study. There are differences in the demographic data among groups although we performed a correction for multiple comparisons. Validation in independent datasets was not performed, although 10-fold cross validation with the internal data was conducted. The results indicated that utilizing wearable devices and machine learning may be useful in identifying depression as well as assessing severity.


Supporting child psychiatric services using current managed care approaches: you can't get there from here.
For-profit behavioral health care companies have transformed the way mental health services are provided for children. Using marketplace approaches, companies have "carved out" mental health services for many patients receiving care from pediatricians. This report details specific approaches used by these firms to maximize profits, minimize the role of child and adolescent psychiatrists, and limit clinical services. Understanding for-profit carveouts will help primary care pediatricians appreciate the likely consequences of such reimbursement incentives for the care of children and their families.


Three-Dimensional Planning and Surgical Technique for Modified Le Fort I and Le Fort III Osteotomy in Non-Syndromic Patients.
Total midface deficiency, to include the orbits, nose, zygomas, and maxilla, can occur in both syndromic and non-syndromic individuals. The treatment with combination of Le Fort III and I osteotomy could be used and it is few reported in the literature. The aim of the study is to present how technology can make the procedure for the correction of hypoplasia of the middle third more predictable and safer. The 2 clinical cases were managed under submental intubation and using VSP that generated 3D printing of oclusal splints and cutting guides. Modified oblique Le Fort III osteotomy (MOLFIIIO) and Le Fort I osteotomy were used due to patients present large sagittal discrepancy between maxilla and mandible (18 and 17 mm). The patients presented good outcomes without complications. In this study, the authors demonstrate that non-syndromic patient could be managed safety with MOLFIII and Le Fort I osteotomies for the correction of midfacial deformities using virtual surgical planning (VSP) associated with 3D printing technique and piezoelectric surgery.


Rejuvenation increases leaf biomass and flavonoid accumulation in Ginkgo biloba.
Rejuvenation refers to the transition from an adult state to a juvenile state. Trunk truncation at the base of the tree can result in tree rejuvenation. However, little is known about the association of rejuvenation with leaf biomass and flavonoid accumulation. The results of this study showed that, compared with control leaves, leaves of renewed Ginkgo biloba shoots were larger, thicker, and more lobed and had higher fresh/dry weights and chlorophyll contents. The leaf biomass per hectare of rejuvenated trees was twofold higher than that of the untruncated controls. Moreover, we observed a marked increase in the accumulation of flavonol glycosides via metabolomic analysis and detected upregulated expression of genes involved in flavonoid biosynthesis, including CHS, FLS, F3'H, DFR, and LAR. Overexpression of GbCHS in ginkgo calli confirmed that GbCHS plays an important role in flavonoid biosynthesis. Interestingly, the contents of gibberellins significantly increased in the rejuvenated leaves. Moreover, exogenous gibberellin treatment significantly increased GbCHS expression and flavonoid contents. Our findings show that truncation can stimulate tree rejuvenation by altering hormone levels, representing an effective and feasible approach for enhancing the biomass and flavonoid content of G. biloba leaves.


[Cecum gangrene as a complication of amyloidosis in myeloma].
It is a report of a rare case of amyloidosis in myeloma with a predominant localization in the caecum wall with the narrowing of blood vessels and a caecum gangrene and peritonitis as complications. Rarity of the case resulted in an erroneous clinical diagnosis and unjustified appendectomy.


Cranial growth in Homo erectus: how credible are the Ngandong juveniles?
Confusion exists regarding the developmental ages of numerous Asian and southeast Asian Homo erectus fossils because of Weidenreich's contention that Pithecanthropus fused its sutures prematurely relative to H. sapiens. I reevaluate the cranial developmental ages of the Ngandong "juveniles" (2, 5, 8, 9) based on a series of indicators of youth (superstructure development, suture development/fusion, and cranial thickness) and cranial contours. The Ngandong juveniles are compared with H. sapiens adults (n = 281) and subadults (n = 81) and with Ngandong and other H. erectus adults (n = 20) and subadults (n = 4). Cranial contours are assessed using bivariate plots of arc vs. chord measurements. All indicators suggest that Ngandong 5 and 9 are adults, whereas Ngandong 8 is an older juvenile or young adult and Ngandong 2 is a juvenile with a developmental age range of greater than 6 and less than 11 years. In addition, adult cranial contours and the pattern of contour development are similar between Ngandong adults and other H. erectus adults. There is nothing in the cranial contour data to suggest that Ngandong is, despite a relatively large brain, transitional in vault shape between H. erectus and H. sapiens.


Challenges of Drug-Facilitated Sexual Assault.
This article provides the reader with an understanding of the numerous challenges of drug-facilitated sexual assaults (DFSA). The challenges are categorized as follows: the drugs, reporting the crime, evidence collection, and laboratory analysis of specimens. The challenges associated with the drugs used to commit DFSA emphasizes the pharmacological effects of strong central nervous system depressants and how the pharmacokinetics and pharmacodynamics of these drugs create difficulties in an investigation. For example, while sexual assaults are generally considered to be a significantly underreported crime, the drug effects further complicate victims' reporting to law enforcement. Any delay in reporting decreases the ability of a laboratory to detect the presence of drugs or metabolites in useful evidentiary specimens such as blood and urine. Finally, differences in instrumentation and mission from one laboratory to the next will impact the ability to provide consistent identification of DFSA drugs or metabolites in these cases. Although the true prevalence of DFSAs will never be fully known, acknowledgment of the many challenges that come with these cases provides insight as to how to improve chances of successfully investigating DFSA allegations.


Medication use in the breastfeeding mother.
Historically, the risks associated with drugs in breast milk were not a major clinical concern. The small percentage of infants who were breastfed and the low use of drugs in postpartum women stimulated little interest in studying medication use in the breastfeeding mother. However, explosive growth in the number of new pharmacologic agents, concerns over environmental contaminants, and a significant increase in breastfeeding, dramatically altered the interest in this clinical issue. Providers of health care to women and children often are asked to advise breastfeeding women on the choice and risks of a particular medication. However, medical professionals too often simply discourage breastfeeding when this situation arises. This short review examines factors that determine whether a drug that enters breast milk poses a risk to the breastfeeding infant. A series of questions and practical decisions are presented that should enable nurses and other health care providers to more effectively address the issue of medication use in a breastfeeding woman.


Treatment of polymyalgia rheumatica and giant cell arteritis. II. Relation between steroid dose and steroid associated side effects.
In a prospective study of 74 patients and a retrospective study of 35 patients with polymyalgia rheumatica/giant cell arteritis steroid related side effects occurred in at least one third of patients, and in two thirds if weight gain was included. Side effects were significantly related to an initial prednisolone dose of more than 30 mg and to the cumulative prednisolone dose. Patients taking a mean daily dose of 5 mg prednisolone or less were significantly less likely to develop side effects.


Breastfeeding and the child cognitive outcomes: a propensity score matching approach.
To estimate the effect of breastfeeding initiation and duration on child development outcomes. 3,271 children and their mothers participating in the Child Development Supplement of the Panel Study of Income Dynamics provide data for these analyses. Main outcomes include Woodcock Johnson Psycho-Educational Battery-Revised (WJ-R) test score (letter word, passage comprehension, applied problem, and broad reading), and Wechsler Intelligence Scale for Children-Revised (WISC-R) test score at the 2002 survey. Controlled variables include family, maternal, and child characteristics, many of which can be traced back to the year the child was born. The analytic technique is propensity score matching with multiple imputations. After using propensity scores to adjust for confounding factors, breastfeeding initiation showed statistically significant effects but the practical scale remains small. Breastfeeding duration showed a non-linear effect on those outcomes and most of the effects are not significant. The effects of breastfeeding on child's cognitive outcomes are modest in practical terms. The non-linear effects suggest that selection into breastfeeding may account for the increased score of children who are breastfed.


Prostate volume and implant configuration during 48 hours of temporary prostate brachytherapy: limited effect of oedema.
In pulsed-dose rate prostate brachytherapy the dose is delivered during 48 hours after implantation, making the treatment sensitive to oedematic effects possibly affecting dose delivery. The aim was to study changes in prostate volume during treatment by analysing catheter configurations on three subsequent scans. Prostate expansion was determined for 19 patients from the change in spatial distribution of the implanted catheters, using three CT-scans: a planning CT (CT1) and two CTs after 24 and 48 hours (CT2, CT3). An additional 4 patients only received one repeat CT (after 24 hours). The mean radial distance (MRD) of all dwell positions to the geometric centre of all dwell positions used was calculated to evaluate volume changes. From three implanted markers changes in inter-marker distances were assessed. The relative shifts of all dwell positions were determined using catheter- and marker-based registrations. Wilcoxon signed-rank tests were performed to compare the results from the different time points. The MRDs measured on the two repeat CTs were significantly different from CT1. The mean prostate volume change derived from the difference in MRD was +4.3% (range -9.3% to +15.6%) for CT1-CT2 (p < .05) and +4.4% (range -7.5% to +16.3%) for CT1-CT3 (p < .05). These values represented a mean increase of 1.2 cm(3) in the first 24 hours and 1.5 cm(3) in the subsequent 24 hours. There was no clear sign of prostate expansion from the change in inter-marker distance (CT1-CT2: 0.2 ± 1.8 mm; CT1-CT3: 0.6 ± 2.2 mm). Catheter configuration remained stable; shifts in catheter positions were largest in the C-C direction: 0 ± 1.8 mm for CT1-CT2 and 0 ± 1.4 mm for CT2-CT3. The volume changes derived from catheter displacements were small and therefore considered clinically insignificant. Implant configuration remains stable during 2 days of treatment, confirming the safety of this technique.


Biocontrol of Salmonella Typhimurium in Raw Salmon Fillets and Scallop Adductors by Using Bacteriophage SLMP1.
The aim of this study was to evaluate the effectiveness of bacteriophage (phage) SLMP1 to reduce Salmonella Typhimurium on contaminated raw salmon fillets and scallop adductors as a function of Salmonella inoculum level, phage dose, storage temperature, and storage time. Samples were inoculated with 102 and 104 CFU/g Salmonella and then treated with different concentrations of phage SLMP1, followed by incubation at 4, 15, and 25°C, respectively. The results showed that 108 PFU/g was the optimal concentration of phage for the control of Salmonella, which was applied in the following storage experiments over a 7-day period at 4°C, a 4-day period at 15°C, and a 2-day period at 25°C. For the salmon fillets samples, 102 CFU/g Salmonella could be reduced below the detection limit at all three temperatures, whereas 104 CFU/g Salmonella was first decreased and then increased at 15 and 25°C. For the scallop adductors samples, 102 CFU/g Salmonella could be reduced below the detection limit first and then increased after a certain period at 15 and 25°C. The variation trends of 104 CFU/g Salmonella in scallop adductors were similar to those in salmon fillets. The results also showed that the Salmonella counts of both inoculum levels on samples could be reduced below the detection limit or maintained at a low level by phage SLMP1 during storage at 4°C. Phage SLMP1 remained stable on raw salmon fillets and scallop adductors. This study indicated that phage SLMP1 has potential effectiveness as a biocontrol agent of Salmonella in seafood.


Ensemble spontaneous activity alterations detected by CISA approach.
In this paper, we propose a method for detecting alterations in the Ensemble Spontaneous Activity (ESA), a random signal representing the composite spontaneous contribution of the auditory nerve recorded on the round window. The proposed method is based on shape analysis of the ESA amplitude histogram. For this task, we use a recent approach, the Corrected Integral Shape Averaging (CISA). Using this approach, a shape clustering algorithm is proposed to classify healthy and pathological ESA signals generated by a recent ESA model. This model allows a precise simulation of neural mechanisms occurring in the auditory nerve. The obtained results demonstrate that this shape analysis is very sensitive for detecting a small number of fibers with correlated firing, supposed to occur during a particular type of tinnitus. In comparison, the classical spectral index fails in this detection.


Ant Colonies Do Not Trade-Off Reproduction against Maintenance.
The question on how individuals allocate resources into maintenance and reproduction is one of the central questions in life history theory. Yet, resource allocation into maintenance on the organismic level can only be measured indirectly. This is different in a social insect colony, a "superorganism" where workers represent the soma and the queen the germ line of the colony. Here, we investigate whether trade-offs exist between maintenance and reproduction on two levels of biological organization, queens and colonies, by following single-queen colonies of the ant Cardiocondyla obscurior throughout the entire lifespan of the queen. Our results show that maintenance and reproduction are positively correlated on the colony level, and we confirm results of an earlier study that found no trade-off on the individual (queen) level. We attribute this unexpected outcome to the existence of a positive feedback loop where investment into maintenance (workers) increases the rate of resource acquisition under laboratory conditions. Even though food was provided ad libitum, variation in productivity among the colonies suggests that resources can only be utilized and invested into additional maintenance and reproduction by the colony if enough workers are available. The resulting relationship between per-capita and colony productivity in our study fits well with other studies conducted in the field, where decreasing per-capita productivity and the leveling off of colony productivity have been linked to density dependent effects due to competition among colonies. This suggests that the absence of trade-offs in our laboratory study might also be prevalent under natural conditions, leading to a positive association of maintenance, (= growth) and reproduction. In this respect, insect colonies resemble indeterminate growing organisms.


Oncogene expression in human leukemia.
The transforming genes of retroviruses (v-onc) are derived from normal cellular genes referred to as proto-oncogenes. These cellular genes have the capacity for conversion to oncogenes (c-onc) that are capable of inducing or maintaining the transformed state when they are overly expressed or altered by mutation or rearrangement. To study the possible involvement of these genes in human leukemia, we have analyzed their expression in a variety of fresh samples. We found that a number of oncogenes are expressed in different leukemic types and that although the transcript size did not vary for each gene, the copy number did. The myc gene (2.4 kb transcript) and the rasHa gene (1.5 kb transcript) were universally expressed. But in contrast to rasHa, the myc signal intensity varied. Myb (4.5 kb transcript) was expressed in all samples except B cell diseases. We detected low levels of abl expression (multiple mRNA species) in all leukemic types analyzed. Sis gene (4.2 kb transcript) expression was restricted to one patient sample with chronic myelogenous leukemia in blast transformation.


Odds Ratio or Prevalence Ratio? An Overview of Reported Statistical Methods and Appropriateness of Interpretations in Cross-sectional Studies with Dichotomous Outcomes in Veterinary Medicine.
One of the most commonly observational study designs employed in veterinary is the cross-sectional study with binary outcomes. To measure an association with exposure, the use of prevalence ratios (PR) or odds ratios (OR) are possible. In human epidemiology, much has been discussed about the use of the OR exclusively for case-control studies and some authors reported that there is no good justification for fitting logistic regression when the prevalence of the disease is high, in which OR overestimate the PR. Nonetheless, interpretation of OR is difficult since confusing between risk and odds can lead to incorrect quantitative interpretation of data such as "the risk is X times greater," commonly reported in studies that use OR. The aims of this study were (1) to review articles with cross-sectional designs to assess the statistical method used and the appropriateness of the interpretation of the estimated measure of association and (2) to illustrate the use of alternative statistical methods that estimate PR directly. An overview of statistical methods and its interpretation using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted and included a diverse set of peer-reviewed journals among the veterinary science field using PubMed as the search engine. From each article, the statistical method used and the appropriateness of the interpretation of the estimated measure of association were registered. Additionally, four alternative models for logistic regression that estimate directly PR were tested using our own dataset from a cross-sectional study on bovine viral diarrhea virus. The initial search strategy found 62 articles, in which 6 articles were excluded and therefore 56 studies were used for the overall analysis. The review showed that independent of the level of prevalence reported, 96% of articles employed logistic regression, thus estimating the OR. Results of the multivariate models indicated that logistic regression was the method that most overestimated the PR. The findings of this study indicate that although there are methods that directly estimate PR, many studies in veterinary science do not use these methods and misinterpret the OR estimated by the logistic regression.


[Determination of energy window width and position for the triple energy window (TEW) scatter compensation method].
Since primary photons can provide information concerning the position of radioisotope (RI) accumulation and the energy of the photons, it would seem reasonable to vary the position and width of the energy window depending on the type of RI and the energy resolution of the detector to collect as many of the primary photons as possible. We propose a method for determining energy window width and position for scintigraphic imaging to collect as many of the primary photons as possible, and studied the influence on the Triple Energy Window (TEW) scatter compensation method of setting such energy window levels for 99mTc (single photopeak) and 201Tl (multiple photopeaks) using detector with different energy resolution through simulation. The Monte Carlo simulations were verified by comparing the regional energy spectrum at the phantom obtained from the simulation against experimental measurements. The energy window with our proposed method for 99mTc is 20% and 47.3% for 201Tl using gamma camera, and 9.8% for 99mTc using a semiconductor detector with a theorized energy resolution of 7.0 keV.


Cardiovascular disease risk factors and dental caries in adolescents: effect of a preventive program in Northern Sweden (the Norsjö project).
Since 1985 a 10 year prevention programme aiming to reduce cardiovascular diseases (CVD) has been running in the county of Västerbotten in Northern Sweden. The project started in Norsjö. The present investigation is a study on dietary intake, medical CVD risk factors and dental caries in five cross-sectional groups of 15-year-olds during 5 years (1987-1991) of the "Norsjö project". Most of the measured medical and dietary variables followed a similar trend, i.e. a positive trend during the first 3 years (1987-1989) and in the last 2 years (1990-1991) the averages returned towards baseline values. Dental caries prevalence followed a similar trend. Parental educational level did not have a major influence on diet or medical CVD risk factors, but higher caries scores were noted in adolescents with parents with "low" education compared with adolescents where the parents had higher educational levels. The results from the study also point to the fact that dental caries prevalence together with body mass index may indicate adolescents with CVD risk factors at unfavourable levels. Dietary counselling by dental personnel to adolescents with high caries and moderate obesity can be of advantage in reducing caries risk, as well as risk for development of CVD at higher ages.