Exploring Breast Cancer Systemic Drug Therapy Patterns in Real-World Data.
To explore medications and their administration patterns in real-world patients with breast cancer. A retrospective study was performed using TriNetX, a federated network of deidentified, Health Insurance Portability and Accountability Act-compliant data from 21 health care organizations across North America. Patients diagnosed with breast cancer between January 1, 2013, and May 31, 2022, were included. We investigated a rule-based and unsupervised learning algorithm to extract medications and their administration patterns. To group similar administration patterns, we used three features in k-means clustering: total number of administrations, median number of days between administrations, and standard deviation of the days between administrations. We explored the first three lines of therapy for patients classified into six groups on the basis of their stage at diagnosis (early as stages I-III v late as stage IV) and the sensitivity of the tumor's receptors to targeted therapies: hormone receptor-positive/human epidermal growth factor 2-negative (HR+/ERBB2-), ERBB2-positive (ERBB2+/HR±), or triple-negative (TN; HR-/ERBB2-). To add credence to the derived regimens, we compared them to the National Comprehensive Cancer Network (NCCN): Breast Cancer (version 2.2023) recommendations. In early-stage HR+/ERBB2- and TN groups, the most common regimens were (1) cyclophosphamide and docetaxel, administered once every 3 weeks for three to six cycles and (2) cyclophosphamide and doxorubicin, administered once every 2 weeks for four cycles, followed by paclitaxel administered once every week for 12 cycles. In the early-stage ERBB2+/HR± group, most patients were administered carboplatin and docetaxel with or without pertuzumab and with trastuzumab (for six or more cycles). Medications most commonly administered in our data set (7,798 patients) agreed with recommendations from the NCCN in terms of medications (regimens), number of administrations (cycles), and days between administrations (cycle length). Although there is a general agreement with the NCCN Guidelines, real-world medication data exhibit variability in the medications and their administration patterns.


Stiff diamond/buckypaper carbon hybrids.
Given the specific properties of each carbon allotrope such as high electrical/thermal conductivity of multiwall carbon nanotubes (MWCNT) and extreme hardness and high inertness of nanocrystalline diamond (NCD), the integration of both carbon phases is highly desirable. Therefore, in the present work, buckypapers were produced from MWCNT suspensions and were used as free-standing substrates to be coated with NCD by microwave plasma chemical vapor deposition (MPCVD). The integration of both allotropes was successfully achieved, the CNTs being preserved after diamond growth as confirmed by μ-Raman spectroscopy and scanning electron microscopy (SEM). Additionally, a good linkage was observed, the CNTs remaining embedded within the NCD matrix, thus reinforcing the interface of the resulting hybrid structure. This was corroborated by bending tests in a modified nanohardness tester. The increase of the Young's modulus from 0.3 to 300 GPa after NCD growth enables the use of this material in a wide range of applications including microelectromechanical systems (MEMS). Additionally, a highly anisotropic electrical resistivity behavior was confirmed: low in-plane values were found for the CNT layer (1.39 × 10(-2) Ω.cm), while high transverse ones were measured for both the NCD coated and uncoated CNT buckypapers (8.13 × 10(5) and 6.18 × 10(2) Ω.cm, respectively).


Intensive induction chemotherapy and delayed irradiation in the management of parameningeal rhabdomyosarcoma.
To evaluate local control, event-free survival, and overall survival for patients with parameningeal (PM) rhabdomyosarcoma (RMS) treated with intensive chemotherapy and delayed irradiation. Thirteen consecutive patients with PM RMS were treated with an institutional protocol from 1992 to 1998 at the University of Washington/Children's Hospital and Regional Medical Center and Deaconess Medical Center. Patients received intensive chemotherapy consisting of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide prior to radiotherapy. Irradiation was delayed, in contrast to current Intergroup Rhabdomyosarcoma Study Group (IRSG) recommendations. Median follow-up was 39 months. Eleven patients had high-risk features, including five with intracranial extension. All patients responded to the intensive chemotherapy, with 38% exhibiting a complete response and the remaining 62% a partial response. Radiation was administered a median of 21 weeks from initiation of chemotherapy. The Kaplan-Meier estimate of 5-year local control was 92%, with event-free survival and overall survival rates of 83%. With intensive induction chemotherapy, delayed irradiation for PM RMS does not compromise local control. Event-free survival and overall survival rates compare favorably with recently IRSG trials employing early irradiation. Delaying irradiation allows for intensification of chemotherapy and could permit response-based radiation volume and/or dose modifications, which could decrease treatment-related morbidity.


Expression of ER, PR, C-erbB-2 and Ki-67 in Endometrial Carcinoma and their Relationships with the Clinicopathological Features.
To analyze the expression of estrogen receptors (ER), progesterone receptors (PR), C-erbB-2 and Ki-67 in endometrial carcinoma (EC) and their relationships with the clinicopathological features. Sixty-seven EC samples, 53 normal endometrial samples and 53 atypical hyperplasia endometrial samples were all selected in Shaanxi Provincial People's Hospital from Jun., 2012 to Jun., 2014. The expression of ER, PR, C-erbB-2 and Ki-67 in EC tissue, normal endometrial tissue and atypical hyperplasia endometrial tissue was respectively detected using immunohistochemical SP method. The relationships between the expression of ER, PR, C-erbB-2 and Ki-67 and the patients' clinicopathological features as well as their correlations in EC tissue were also analyzed. The positive expression rates of ER and PR in EC tissue were 44.8% and 41.8%, respectively, dramatically lower than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). The positive expression rates of C-erbB-2 and Ki-67 in EC tissue were 80.6% and 64.2%, respectively, significantly higher than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). In EC tissue, the expression of ER and PR was closely associated with the differentiated degrees and depth of myometrial invasion (P<0.05), while that of C-erbB-2 and Ki-67 with the clinical staging, differentiated degrees, depth of myometrial invasion and presence or absence of lymph node metastasis (P<0.05). Spearman correlation analysis further displayed that the expression of ER was positively correlated with PR (r=0.393, P=0.001), but negatively with C-erbB-2 and Ki-67 (r=-0.469, P=0.000; r=-0.329, P=0.007); The expression of PR was negatively correlated with C-erbB-2 and Ki-67 (r=-0.273, P=0.025; r=-0.251, P=0.041), but that of C-erbB-2 positively with Ki-67 (r=0.342, P=0.005). Abnormal expression of ER, PR, C-erbB2 and Ki-67 might play an important role in endometrial malignant transformation and cell differentiation, so their joint detection is likely to be a comprehensive combination of immune factors, which is of great importance for EC prognosis.


Integrating trait and social-cognitive views of personality: neuroticism, implicit stress priming, and neuroticism-outcome relationships.
The trait perspective of personality emphasizes the broad role of traits in outcome prediction, whereas the social-cognitive perspective emphasizes the importance of if-then intrapsychic associations. Three studies (N = 188) were conducted to reconcile these alternative views of personality in the context of stress-related behaviors. Implicit priming tasks were used to quantify the extent to which stress primes activated thoughts of aggression (Studies 1 and 2) or eating (Study 3), and trait levels of neuroticism were also assessed. Neuroticism did not consistently predict stress-related implicit associations, consistent with the independence of these predictors. Of more importance, such implicit associations predicted problematic outcomes (e.g., physical aggression), but only to the extent that relevant individuals were also high in neuroticism. The results highlight an interface of trait and social-cognitive views of personality and do so in the context of understanding stress-reactivity processes, a topic of importance to multiple literatures.


Application of guided imagery to facilitate the transition of new graduate registered nurses.
Traditionally, the new graduate registered nurse (RN) transition has included a didactic and skills-based orientation accompanied by a period of preceptored practice. However, these methods do not ensure that new RNs are in a state of reduced anxiety to fully interact with their new environment. Transition to practice may cause anxiety, and the new graduate RN may perceive moderate to severe stress. One method of stress reduction is the use of guided imagery, which has shown strong potential with a variety of populations undergoing stressful events. Today, new graduate RNs expect institutions to facilitate orientation to their new employment settings and assist in the transition to their role as a professional nurse. This article proposes a model that incorporates guided imagery for refining the new graduate RN transition process. The model can be adapted for use in the context of orienting other adult learners to unfamiliar practice situations.


Community level evaluation of adenoid hypertrophy on the basis of symptom scoring and its X-ray correlation.
One of the major causes of pediatric morbidity today at the community level is infection involving the ear, nose, and throat. Maximum of these patients respond well initially on general regular medications, but then recurrent complaints are not very uncommon. One of the major causes for such recurrence is hypertrophy of adenoids, the evaluation of which requires a battery of sophisticated investigative tools and expertise which are lacking at the community level. The aim of the study is to evaluate various symptoms related to adenoid hypertrophy and its correlation to the size of the adenoid seen in the lateral view nasopharyngeal X-ray. The aim of the study was to assess various symptoms related to adenoid hypertrophy and its correlation with the size of adenoid radiologically. A total of fifty cases of pediatric age with strong clinical suspicion of adenoid hypertrophy were included in the study. Through ENT examination was done. X-ray lateral view nasopharynx was obtained. Adenoid hypertrophy was graded according to symptoms score and lateral cephalometric/radiographs. Snoring was the most frequent symptom which had a linear relation with the size of the adenoid. There was good agreement between symptom and the X-ray findings.


Failure of anti-TSH receptor antibodies (TRAb) to predict the outcome of the course of Graves' disease following withdrawal of antithyroid drug.
Nineteen patients with Graves' disease were regarded as euthyroid at the end of therapy. Follow-up studies were performed for further 3 years. TSH binding inhibitor immunoglobins (TBII) were measured by radioreceptor assay. Thyroid stimulating antibodies (TSAb) were measured by a sensitive cAMP accumulation using FRTL-5 cells. Most of the patients showed negative TBII at the end of therapy, while TSAb-positive patients were approximately 50%. The relapse rates during post therapeutic period were 33.3% in TSAb-positive group and 40% in TSAb-negative group, which were not significantly different between the two groups. It was thought that determination of TSAb activity at the end of therapy, in addition to TBII, appears to play a permissive role in predicting the outcome of the course of Graves' disease following discontinuation of antithyroid drug therapy.


Screening for drugs of abuse in oral fluid--correlation of analysis results with serum in forensic cases.
The testing of saliva or oral fluid at the roadside could be a powerful tool to detect drivers under the influence of drugs and has several advantages over urine screening. In 177 cases of individuals suspected of driving under the influence of drugs, oral fluid was collected at the roadside and analyzed in parallel to serum samples. The study was performed to investigate the variability of oral fluid analysis results in relation to blood/serum. In 45% of the cases single-drug use was found, and in 50% poly-drug use was found. Cannabis was most prevalent (78%), and 70% of these individuals were also positive for tetrahydrocannabinol in serum. Overall, 97% of oral fluid samples positive for any substance were also positive in serum. Comparing data of oral fluid and serum for amphetamine, MDMA, morphine, benzoylecgonine, and tetrahydrocannabinol, the sensitivities were 100%, 97%, 87%, 87%, and 92%, respectively. Overall specificity and accuracy were in the range of 91-98%. Discrepancies between a negative oral fluid sample and a positive serum sample could be explained by analytical insensitivity in the lower volume of oral fluid analyzed (estimated for 0.1 mL confirmation vs. 1 mL of serum) or a shorter detection window in oral fluid. The low prevalence of discrepancies with positive oral fluid and negative serum results (2-9% of the cases) may be explained by persistent oral contamination especially for orally consumed drugs, like MDMA and cannabis. It is concluded that the detection of a psychoactive substance in oral fluid taken at the roadside is highly predictive for the detection of the corresponding drug or its metabolite in serum. Oral fluid testing is therefore suitable for the efficient confirmation of drug use of drivers suspected of being under the influence of drugs.


Branched-chain amino acid, meat intake and risk of type 2 diabetes in the Women's Health Initiative.
Knowledge regarding association of dietary branched-chain amino acid (BCAA) and type 2 diabetes (T2D), and the contribution of BCAA from meat to the risk of T2D are scarce. We evaluated associations between dietary BCAA intake, meat intake, interaction between BCAA and meat intake and risk of T2D. Data analyses were performed for 74 155 participants aged 50-79 years at baseline from the Women's Health Initiative for up to 15 years of follow-up. We excluded from analysis participants with treated T2D, and factors potentially associated with T2D or missing covariate data. The BCAA and total meat intake was estimated from FFQ. Using Cox proportional hazards models, we assessed the relationship between BCAA intake, meat intake, and T2D, adjusting for confounders. A 20 % increment in total BCAA intake (g/d and %energy) was associated with a 7 % higher risk for T2D (hazard ratio (HR) 1·07; 95 % CI 1·05, 1·09). For total meat intake, a 20 % increment was associated with a 4 % higher risk of T2D (HR 1·04; 95 % CI 1·03, 1·05). The associations between BCAA intake and T2D were attenuated but remained significant after adjustment for total meat intake. These relations did not materially differ with or without adjustment for BMI. Our results suggest that dietary BCAA and meat intake are positively associated with T2D among postmenopausal women. The association of BCAA and diabetes risk was attenuated but remained positive after adjustment for meat intake suggesting that BCAA intake in part but not in full is contributing to the association of meat with T2D risk.


Randomized controlled trial on the effect of Al-Quran recitation vs counseling on smoking intensity among Muslim men who are trying to quit smoking.
Nicotine cravings and withdrawal symptoms are associated with higher rates of relapse. It has been shown that combining behavioral therapy and pharmacotherapy leads to a higher long-term abstinence rate in those who quit smoking. Al-Quran recitation has been proven to reduce anxiety among athletes before tournaments and pulse and heart rates among patients awaiting cardiac operations. As most of the patients who wish to stop smoking experience high-anxiety states, we postulate that Al-Quran recitation will also able to reduce craving among smokers attempting to quit smoking. Fifty smokers from an outpatient clinic were randomly assigned to control and intervention groups. They were taught different ways of coping with smoking urges, i.e., counseling using the 12'M' method (control group) versus Al-Quran recitation (intervention group). They met for four consecutive weeks of counselling and to fill out a withdrawal scale. Carbon monoxide (CO) levels were tested at baseline and at week 4. At week 12, the number of cigarettes smoked was measured again. The decrease in the number of cigarettes considered to be clinically significant for the calculation of sample size was based on expert opinion. The reduction in the number of cigarettes smoked was 7 cigarettes in the counselling group and 9 cigarettes in Al-Quran recitation group over 12 weeks duration. There was a statistically significant difference in the number of cigarettes smoked between the groups. There was also a statistically significant difference in the change in cravings between the groups at week 4 (p-value = 0.005). However, the difference in the changes in CO levels between the two groups was not statistically significant. Al-Quran recitation produced a statistically significant reduction in the number of cigarettes smoked at week 12 and a significant change in cravings at week 4 among smokers attempting to quit. Difference in smoking abstinence rates was not measured in this study.


Purification and DNA-binding activity of the PacA subunit of the bacteriophage P1 pacase enzyme.
The bacteriophage P1 packaging site (pac) cleavage enzyme (pacase) consists of two phage encoded proteins, PacA and PacB. Both proteins are necessary for the recognition and cleavage of pac and for subsequent packaging of cleaved DNA into phage particles. We have purified PacA to homogeneity from a bacterial strain that overproduces the protein. Purified PacA complements an Escherichia coli extract containing the PacB protein for DNA cleavage at the pac site and recognizes and binds to methylated pac DNA independently of PacB in gel retardation experiments. The latter property of PacA is absolutely dependent on the presence of a wildtype E. coli extract, suggesting that E. coli host proteins play a role in the pac cleavage reaction.


Strategies for developing novel therapeutics for sensorineural hearing loss.
Sensorineural hearing loss (SNHL) is a common disability in the world; however, at present, options for the pharmacological treatment of SNHL are very limited. Previous studies involving human temporal bone analyses have revealed that the degeneration of the cochlea is a common mechanism of SNHL. A major problem for the development of novel pharmacotherapy for SNHL has been the limited regeneration capacity in mammalian cochlear cells. However, recent progress in basic studies has led to several effective strategies for the induction of regeneration in the mammalian cochlea, in accordance with the stage of degeneration. In addition, recent advances in the identification of human deafness genes and their characterization in mouse models have elucidated cellular and/or molecular mechanisms of SNHL, which will contribute to clarify molecular targets of pharmacotherapy for treatment of SNHL.


Respiratory failure secondary to human metapneumovirus requiring extracorporeal membrane oxygenation in a 32-month-old child.
Human metapneumovirus (HMPV) is a common virus that can cause respiratory problems ranging from mild upper respiratory tract disease to respiratory failure requiring mechanical support. Here, we report a case of a 32-month-old male with a previous history of asthma, who developed respiratory failure two weeks after onset of cough and rhinorrhea and required extracorporeal membrane oxygenation (ECMO) for 9 days after failing high-frequency oscillatory ventilation (HFOV). To our knowledge, this is the oldest reported pediatric patient with respiratory failure secondary to human metapneumovirus that did not respond to mechanical ventilation. This case highlights three critical points: the potentially fatal causative role of HMPV in respiratory failure in an older pediatric age group of immunocompetent hosts, the importance of early recognition of impending respiratory failure, and the timely utilization of ECMO.


qBinning: Data Quality-Based Algorithm for Automized Ion Chromatogram Extraction from High-Resolution Mass Spectrometry.
Due to the complexity and volume of data generated through non-target screening (NTS) using chromatographic couplings with high-resolution mass spectrometry, automized processing routines are necessary. The processing routines usually consist of many individual steps that are user-parameter-dependent and, thus, require labor-intensive optimization. Additionally, the effect of variations in raw data quality on the processing results is unclear and not fully understood. Within this work, we present qBinning, a novel algorithm for constructing extracted ion chromatograms (EICs) based on statistical principles and, thus, without the need to set user parameters. Furthermore, we give the user feedback on the specific qualities of the generated EICs using a scoring system (DQSbin). The DQSbin measures reliability as it correlates with the probability of correct classification of masses into EICs and the degree of overlap between different EIC construction algorithms. This work is a big step forward in understanding the behavior of NTS data and increasing the overall transparency in the results of NTS.


The Role of Oncofertility Clinics in Facilitating Access to Reproductive Specialists.
To determine the impact of the establishment of a dedicated oncofertility clinic on the frequency of patient referrals for fertility preservation (FP) consultation and the time from patient referral to consultation. A retrospective chart review of all women aged 21 to 44 years with an active cancer diagnosis who were referred for FP consultation from 2011 to 2015. A total of 6895 female patients eligible for FP were seen at the Massachusetts General Hospital (MGH) Cancer Center. Of those eligible, a total of 209 patients were referred for FP consultation with 150 included in the final analysis. Since the establishment of the oncofertility clinic, the mean time to nonemergent consultation with a reproductive endocrinologist decreased by 27%, from 10.4 to 7.6 days (P = .03). Furthermore, the proportion of reproductive-aged females seen at the MGH Cancer Center referred for FP consultation increased from 1.7% to 3.0% (P < .01). A dedicated oncofertility clinic increases physician referrals for FP and decreases the mean time to consultation, improving access to FP consultation for reproductive-aged women with cancer.


Battery-free temperature logger for deep-sea hydrothermal fluids based on heat pipe heat exchangers and thermoelectric generators.
Long-term in situ measurements of the temperature of hydrothermal fluids have great significance in the research of seafloor hydrothermal activities. Herein, we developed a self-powered battery-free temperature logger for measuring and recording the temperature of hydrothermal fluids. A gravity heat pipe made of titanium alloy was employed as the heat-conducting element of the temperature logger to capture heat from a hydrothermal vent and transfer it to the thermoelectric unit. The thermoelectric generator used herein converted the temperature difference into electrical energy to power the circuit of the temperature logger. Numerical analyses and experiments were performed to investigate the performance of the heat pipe and temperature logger. Results show that the temperature logger can realize self-powered starting at a temperature of >76 °C during a tank test. This paper presents a discussion on a new instrument for temperature measurements of deep-sea hydrothermal fluids.


Phase retrieval from speckle images.
In ground-based astronomy, the inverse problem of phase retrieval from speckle images is a means to calibrate static aberrations for correction by active optics. It can also be used to sense turbulent wavefronts. However, the number of local minima drastically increases with the turbulence strength, mainly because of phase wrapping ambiguities. Multifocal phase diversity has been considered to overcome some ambiguities of the phase retrieval problem. We propose an effective algorithm for phase retrieval from a single focused image. Our algorithm makes use of a global optimization strategy and an automatically tuned smoothness prior to overcome local minima and phase degeneracies. We push the limit of D/r(0)=4 achieved by Irwan and Lane [J. Opt. Soc. Am. A.15, 2302 (1998)] up to D/r(0)=11, which is a major improvement owing to the drastic increase in the problem complexity. We estimate the performances of our approach from consistent simulations for different turbulence strengths and noise levels (down to 1500 photons per image). We also investigate the benefit of temporal correlation.


[Serratia marcescens vaccine in the treatment of malignant pleural effusion].
To evaluate the efficacy and toxicity of Serratia marcescens (S311) vaccine in the treatment of malignant pleural effusion. Thirty-four patients with malignant pleural effusion were given S311 as intrapleural injection with a dose of 10(9) U (0.32 mg) on D 1, 8 and 15, and observed for four weeks. The overall response rate (CR + PR) was 97.1% (CR in 12 patients and PR in 21 patients). The systemic toxicity was mild, including fever (82.4%), pleuritic pain (50.7%), nansea (26.5%), dyspnea (17.5%) and chills (5.9%). Serratia marcescens vaccine is effective for malignant pleural effusion, with tolerable toxic effects. Further study is warranted.


Marijuana: Views on Its Medical Use Recorded at the Slovak Social Network.
We describe opinions on medical use of Cannabis sativa L under conditions of Slovakia (n = 717). Personal experience with marijuana was detected in 77.42% (n = 553) in age categories younger than 20 years (n = 96) and in 77.06% (n = 457) of adults. Almost 86% of respondents (n = 618) agreed with legal use of marijuana for medical purposes. Furthermore, respondents' views on legal usage of marijuana for medical purposes could be affected by availability of information (r = .12) and personal experience (r = .23). Negative impact of substance abuse in younger age-groups was recognized as threat (r = .47), but knowledge about harmful effect of marijuana use did not affect personal opinion for decriminalization (r = .38).


Effect of Crotalus basiliscus snake venom on the redox reaction of myoglobin.
In this work, we have studied the effect of Crotalus basiliscus snake venom on the redox reaction of myoglobin (Mb), and by means of electrochemical techniques, we have shown that this reaction is undoubtedly affected following the interaction with the venom. Surface plasmon resonance, electrophoresis, UV-Vis, and circular dichroism showed that the interaction involves the attachment of some constituent of the venom to the protein, although not affecting its first and secondary structures. Mass spectra support this suggestion by showing the appearance of signals assigned to the Mb dimer and to a new species resulting from the interaction between Mb and the venom proteins. In addition, the mass spectra suggest the aromatic amino acids of myoglobin, mainly tryptophan and phenylalanine, are more exposed to the solvent medium upon the exposure to the venom solution. The results altogether indicate that the harmful effects of the venom of Crotalus basiliscus snake are likely connected to the blocking of the redox site of Mb.


Pulmonary and sinusal changes in 45 patients with primary immunodeficiencies: computed tomography evaluation.
The aims of the study were 1) to identify and quantify pulmonary changes in subjects affected by agammaglobulinemia (AG), and common variable immunodeficiency (CVID) and 2) to assess the incidence, type, and degree of chronic sinusitis and their relation to pulmonary changes. Forty-five patients affected by AG (18) and CVID (27) underwent computed tomography of lungs and paranasal sinuses. Of 45 patients, 26 (57.7%) had pulmonary changes, more frequent among CVID than AG patients (P = 0.37). Bronchiectases were detected in 7 of 12 AG and in 9 of 14 CVID; the difference is not statistically significant (P = 0.53). Computed tomographic findings of chronic sinusitis were detected in 41 of 45 patients. There was no statistically significant difference between AG and CVID patients. Bronchial and sinusal abnormalities did not correlate in 11 patients followed longitudinally. On computed tomography, the type and severity of lung lesions do not correlate either with the type of immunodeficiency or with the severity of the sinusal involvement.


Brain damage during cardiopulmonary bypass.
The development of systems that allow cardiopulmonary bypass have been responsible for the growth of our specialty. In recent years continuing reduction in the mortality associated with cardiac operations has reinforced our confidence in the reliability and safety of perfusion equipment. Cardiac surgeons are aware that the mortality for most cardiac surgical procedures has decreased dramatically and overall morbidity has been reduced significantly. However, it is still clear that cardiopulmonary bypass techniques are not perfect. Indeed, it is fair to say that the period of bypass still contributes to significant morbidity in most patients. In particular, cerebral injury, the focus of this review, is a significant problem for patients and their caregivers and for funding of health-care systems. Incidence rates for stroke are around 2% to 3%, with increased risk in elderly patients and other high-risk groups. This relatively low incidence of what is universally recognized as a serious complication may be contrasted with the much higher reported incidence of cognitive defects assessed by neuropsychologic testing. The incidence of cognitive defects is as high as 60% at 8 days postoperative with reduction to 25% to 30% incidence at 8 weeks and 12 months. There are a variety of ways, at least potentially, in which the brain may be injured during an operation with cardiopulmonary bypass, including reduced cerebral blood flow, microembolism and macroembolism, and a systemic inflammatory response. These mechanisms interrelate and produce synergistic, cumulative effects on brain function during and after the operation. Reducing the incidence and effects of this altered brain function will rely on both preventive and therapeutic strategies. These, in turn, must be based on an understanding of the pathophysiology of these mechanisms of cerebral injury and directed toward ways to optimize cerebral perfusion, minimize embolic vascular occlusion, and develop pharmacologic approaches to modify the systemic inflammatory response.


Overview of the structure and function of the dopamine transporter and its protein interactions.
The dopamine transporter (DAT) plays an integral role in dopamine neurotransmission through the clearance of dopamine from the extracellular space. Dysregulation of DAT is central to the pathophysiology of numerous neuropsychiatric disorders and as such is an attractive therapeutic target. DAT belongs to the solute carrier family 6 (SLC6) class of Na+/Cl- dependent transporters that move various cargo into neurons against their concentration gradient. This review focuses on DAT (SCL6A3 protein) while extending the narrative to the closely related transporters for serotonin and norepinephrine where needed for comparison or functional relevance. Cloning and site-directed mutagenesis experiments provided early structural knowledge of DAT but our contemporary understanding was achieved through a combination of crystallization of the related bacterial transporter LeuT, homology modeling, and subsequently the crystallization of drosophila DAT. These seminal findings enabled a better understanding of the conformational states involved in the transport of substrate, subsequently aiding state-specific drug design. Post-translational modifications to DAT such as phosphorylation, palmitoylation, ubiquitination also influence the plasma membrane localization and kinetics. Substrates and drugs can interact with multiple sites within DAT including the primary S1 and S2 sites involved in dopamine binding and novel allosteric sites. Major research has centered around the question what determines the substrate and inhibitor selectivity of DAT in comparison to serotonin and norepinephrine transporters. DAT has been implicated in many neurological disorders and may play a role in the pathology of HIV and Parkinson's disease via direct physical interaction with HIV-1 Tat and α-synuclein proteins respectively.


Deep Venous Thrombosis and Pulmonary Embolism: Current Therapy.
Pulmonary embolism and deep venous thrombosis are the two most important manifestations of venous thromboembolism (VTE), which is the third most common life-threatening cardiovascular disease in the United States. Anticoagulation is the mainstay of VTE treatment. Most patients with deep venous thrombosis or low-risk pulmonary embolism can be treated in the outpatient setting with low-molecular-weight heparin and a vitamin K antagonist (warfarin) or direct-acting oral anticoagulants. Inpatient treatment of VTE begins with parenteral agents, preferably low-molecular-weight heparin. Unfractionated heparin is used if a patient is hemodynamically unstable or has severe renal insufficiency, high bleeding risk, hemodynamic instability, or morbid obesity. Direct-acting oral anticoagulants are an alternative; however, concerns include cost and use of reversing agents (currently available only for dabigatran, although others are in development). If warfarin, dabigatran, or edoxaban is used, low-molecular-weight or unfractionated heparin must be administered concomitantly for at least five days and, in the case of warfarin, until the international normalized ratio becomes therapeutic for 24 hours. Hemodynamically unstable patients with a low bleeding risk may benefit from thrombolytic therapy. An inferior vena cava filter is not indicated for patients treated with anticoagulation. Current guidelines recommend anticoagulation for a minimum of three months. Special situations, such as active cancer and pregnancy, require long-term use of low-molecular-weight or unfractionated heparin. Anticoagulation beyond three months should be individualized based on a risk/benefit analysis. Symptomatic distal deep venous thrombosis should be treated with anticoagulation, but asymptomatic patients may be monitored with serial imaging for two weeks and treated only if there is extension.


Rhythm vs. Rate Control in Patients with Postoperative Atrial Fibrillation after Cardiac Surgery: A Systematic Review and Meta-Analysis.
Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery; it is associated with morbidity and mortality. We undertook this review to compare the effects of rhythm vs. rate control in this population. We searched MEDLINE, Embase and CENTRAL to March 2023. We included randomized trials and observational studies comparing rhythm to rate control in cardiac surgery patients with POAF. We used a random-effects model to meta-analyze data and rated the quality of evidence using GRADE. From 8,110 citations, we identified 8 randomized trials (990 patients). Drug regimens used for rhythm control included amiodarone in four trials, other class III anti-arrhythmics in one trial, class I anti-arrhythmics in four trials and either a class I or III anti-arrhythmic in one trial. Rhythm control compared to rate control did not result in a significant difference in length of stay (mean difference -0.8 days; 95% CI -3.0 to +1.4, I2 = 97%), AF recurrence within 1 week (130 events; risk ratio [RR] 1.1; 95%CI 0.6-1.9, I2 = 54%), AF recurrence up to 1 month (37 events; RR 0.9; 95%CI 0.5-1.8, I2 = 0%), AF recurrence up to 3 months (10 events; RR 1.0; 95%CI 0.3-3.4, I2 = 0%) or mortality (25 events; RR 1.6; 95%CI 0.7-3.5, I2 = 0%). Effect measures from seven observational studies (1428 patients) did not differ appreciably from those in randomized trials. Although atrial fibrillation is common after cardiac surgery, limited low-quality data guide its management. Limited available evidence suggests no clear advantage to either rhythm or rate control. A large-scale randomized trial is needed to inform this important clinical question.


Magnesium sulfate administration in subarachnoid hemorrhage.
Magnesium offers theoretic vascular and neuroprotective benefits for patients with subarachnoid hemorrhage. An electronic literature search was conducted to identify original research studies describing intravenous magnesium treatment in patients with SAH published in English between January 1990 and October 2010. Seventeen articles were identified and reviewed, including one phase III randomized-controlled clinical trial and six phase II randomized-controlled trials. Study quality was low for most of the included studies, with the phase III trial considered to be of moderate quality. Due to inconsistently reported benefits and the occurrence of side effects, phase II data suggested that intravenous magnesium for SAH provided either no overall net benefit or uncertain trade-offs. Benefit was likewise not supported in the single phase III clinical trial.


Acid-cleavable polymeric core-shell particles for delivery of hydrophobic drugs.
Here we describe the combined use of acid-labile microgel approach and RAFT-mediated seeded dispersion polymerization technique to prepare an acid-cleavable core-shell like polymeric colloidal system for the delivery of hydrophobic drugs at slightly acidic sites. A new bisacrylate acetal crosslinker was copolymerized with n-butyl acrylate (BA) in the presence of a RAFT agent using a dispersion polymerization technique, which yielded crosslinked spherical particles with the size ranging between 150 and 500 nm. The particles were cleaved in a pH-dependent manner similar to the acid-labile hydrolysis behaviour of the crosslinker. In order to mask the hydrophobic surface of the particles, polyethylene glycol acrylate (PEG-A) was grafted onto poly(BA) seed particles via the RAFT agent groups on the particle surface. The acidic-site selective delivery potential of the poly(BA)-g-poly(PEG-A) particles was assessed in-vitro using a lipophilic fluorescent dye as a model hydrophobic drug. Ca. 73% and 34% of the total dye loaded in the particles was found to be released at pH 5.0 and 7.4 in 24 h, respectively. The growth of human neuroblastoma cells was not affected by the incubation with the core-shell particles and their cleavage by-products up to 3 mg/ml concentration. The physicochemical and the functional features support the potential value of the acid-cleavable poly(BA) core-poly(PEG-A) shell particles as carriers for the delivery of hydrophobic drugs at acidic sites.


[Manual endothelial cell enumeration for transplanted corneas in comparison to software controlled, automatic enumeration].
The evaluation of the endothelial cells is the most important criterion for assessing human donor corneas. The number, morphology and the vitality of the endothelial cells are decisive for the transparency of a cornea. The study has the following aim: to verify whether there is any difference between the manual and the automatic count of the cells by means of the NAVIS(R) system. Both methods were performed on 57 corneas of 35 patients. A photo was taken for the manual count by a microscope at 40-fold enlargement and was printed for further analysis. A grid was applied to this photo and the number of the endothelial cells was projected by a multiplicator to one square millimeter. For the automatic evaluation a picture was made with 20-fold microscopic enlargement; the examiner chose an area to be analysed. There the count of the cells was controlled by software and directly projected to one square millimetre. This was followed by a manual correction. The measurement data were statistically evaluated. No statistically significant difference was found between the manual and automatic counts. The manual count of the endothelial cells can be replaced by software-controlled automatic analysis and count.


Vigilance has mainly a social function in a wild group of spider monkeys (Ateles geoffroyi).
Vigilance is a widespread behavior that allows individuals to socially acquire information and/or effectively detect potential risks posed by predators and conspecifics. In this study, we aimed to investigate how social factors (i.e., subgroup size, number of males and immatures in the subgroup, presence of fission and fusion events, subgroup activity), individual characteristics (i.e., sex, presence of dependent offspring) and possible vulnerability to predation (i.e., being in smaller subgroups or lower in the canopy) explain variation in vigilance behavior in a wild group of spider monkeys (Ateles geoffroyi). We collected vigilance data during focal samples of all adults, subadults and juveniles of the group (N = 38), and ran generalized linear mixed models with a Bayesian approach. We found that the proportion of time both sexes spent in vigilance increased with subgroup size and during fusion events. Individuals also spent more time in vigilance when the subgroup was resting or socializing compared to other activities. Moreover, the proportion of time spent in vigilance increased in subgroups with more immatures. An alternative model with similar fit suggested that the proportion of time spent in vigilance increased in females when subgroups included more adult and subadult males. Overall, these results suggest that our study group mainly directed vigilance toward conspecifics (i.e., social vigilance), probably as a result of the relatively low predation pressure experienced, and contribute to the understanding of the multiple social factors affecting vigilance in group-living primates.


Disease Management in the Genomics Era-Summaries of Focus Issue Papers.
The genomics revolution has contributed enormously to research and disease management applications in plant pathology. This development has rapidly increased our understanding of the molecular mechanisms underpinning pathogenesis and resistance, contributed novel markers for rapid pathogen detection and diagnosis, and offered further insights into the genetics of pathogen populations on a larger scale. The availability of whole genome resources coupled with next-generation sequencing (NGS) technologies has helped fuel genomics-based approaches to improve disease resistance in crops. NGS technologies have accelerated the pace at which whole plant and pathogen genomes have become available, and made possible the metagenomic analysis of plant-associated microbial communities. Furthermore, NGS technologies can now be applied routinely and cost effectively to rapidly generate plant and/or pathogen genome or transcriptome marker sequences associated with virulence phenotypes in the pathogen or resistance phenotypes in the plant, potentially leading to improvements in plant disease management. In some systems, investments in plant and pathogen genomics have led to immediate, tangible benefits. This focus issue covers some of the systems. The articles in this focus issue range from overall perspective articles to research articles describing specific genomics applications for detection and control of diseases caused by nematode, viral, bacterial, fungal, and oomycete pathogens. The following are representative short summaries of the articles that appear in this Focus Issue .


Child undernutrition in households with microbiologically safer drinking water and 'improved water' in Tanna, Vanuatu.
The Sustainable Development Goal drinking water indicators include microbiological safety measures, whereas the Millennium Development Goal indicator 'improved water' may be microbiologically unsafe. In rural Vanuatu, we undertook household surveys, child anthropometry, and tested stored drinking water, to investigate relationships between water and undernutrition. Using Escherichia coli most probable number, we categorized results according to Compartment Bag Test drinking water cutoffs: <1/100 mL (safe), 1-10/100 mL (intermediate risk), >10-100/100 mL (high risk), and >100/100 mL (very high risk). Of 201 households, 191 (95%) had microbiologically unsafe drinking water, regardless of 'improved' status. We investigated cross-sectional associations between households with microbiologically safer drinking water (≤10 E. coli/100 mL) versus 'improved water' and undernutrition among children. Of children under 5, 145 (48.8%, 95% CI: 42.8, 54.8) were stunted and 59 (19.1%, 95% CI: 14.4, 23.8) were underweight. Among households with 'improved water', the adjusted prevalence ratio (95% CI) of stunting was 0.61 (0.46, 0.80) and underweight was 0.46 (0.29, 0.73) compared with 'unimproved water'. However, we found no association between having drinking water with ≤10 E. coli/100 mL at one point in time and undernutrition. Longer-term variations in water quality and unmeasured conditions beyond water may have contributed to these associations.


Quantitative benefit-risk analysis for evaluating drug therapies.
Despite the fact that benefit-risk analysis is a necessary component of the review of new drugs for potential regulatory approval in the presence of known adverse side effects, and of the review of already-approved drugs for possible withdrawal from the market when unanticipated adverse events are discovered, formal quantitative tools for benefit-risk analysis are few. This paper proposes a quantitative method that utilizes receiver operating characteristic (ROC) curves to find an optimal dose of a drug that maximizes the differential between the benefit of the intended effect and the risk of adverse side effects, where costs associated with lack of benefit and risk can be incorporated. The method can be applied separately to subpopulations of different sensitivities and to different adverse events to give a full picture of the trade-offs between the benefit afforded by the drug and the risk it incurs, and potentially to allow the drug to be approved only selectively for specific subpopulations, or at different doses for different subpopulations.


Taxonomy of the antibiotic Bu-2313-producing organism. Microtetraspora caesia sp. nov.
An aerobic actinomycete strain isolated from an Indian soil sample and designated No. E864-61 was found to produce in submerged fermentation a new antibiotic complex, Bu-2313 (components A and B). Strain E864-61 forms single, pairs or chains of three to eight spores on the aerial mycelium and its aerial mass color is grayish blue-green. The cell wall of strain E864-61 contains meso-diaminopimelic acid and galactose. Strain E864-61 has been classified as a new species of the genus Microtetraspora and designated as Microtetraspora caesia sp. nov.


Predator-mediated allee effects in multi-prey systems.
Allee effects can have significant consequences for small populations and understanding the causal mechanisms for such effects is important for guiding conservation actions. One proposed mechanism is through predation, in which a type II functional response leads to increasing predation rates as prey numbers decline. However, models to support this mechanism have incorporated only a single declining prey species in the functional response, which is probably an oversimplification. We reevaluated the potential for predator-mediated Allee effects in a multi-prey system using Holling's disc equation. We also used empirical data on a large herbivore to examine how grouping behavior may influence the potential for predation-mediated Allee effects. Results based on a multi-prey expression of the functional response predict that Allee effects caused by predation on relatively rare secondary prey may not occur because handling time of the abundant prey dominates the functional response such that secondary prey are largely "bycatch". However, a predator-mediated Allee effect can occur if secondary prey live in groups and if, as the population declines, their average group size declines (a relationship seen in several species). In such a case, the rate at which the number of groups declines is less than the rate at which the population declines. Thus the rate at which a predator encounters a group remains relatively stable, but when a predator kills one animal from smaller groups, the predation rate increases. These results highlight the need to evaluate risks associated with potential changes in group size as populations decline.


[Analysis of the dopamine D2 receptor gene].
The methods, such as Southern blot hybridization, PCR-direct sequencing and PCR-SSCP, to detect sequence variants in the human dopamine D2 receptor (DRD2) gene were described. To study the association of a missense variant of the DRD2 gene resulting in Ser311-->Cys, which was detected by PCR-direct sequencing in schizophrenics, the genotypes of controls and schizophrenics were determined by the methods of PCR-dot blot hybridization, PCR amplification of specific alleles and artificially introduced PCR-RFLP.


The effect of requesting a reason for non-adherence to a guideline in a long running automated reminder system for PONV prophylaxis.
Automated reminders are employed frequently to improve guideline adherence, but limitations of automated reminders are becoming more apparent. We studied the reasons for non-adherence in the setting of automated reminders to test the hypothesis that a separate request for a reason in itself may further improve guideline adherence. In a previously implemented automated reminder system on prophylaxis for postoperative nausea and vomiting (PONV), we included additional automated reminders requesting a reason for non-adherence. We recorded these reasons in the pre-operative screening clinic, the OR and the PACU. We compared adherence to our PONV guideline in two study groups with a historical control group. Guideline adherence on prescribing and administering PONV prophylaxis (dexamethasone and granisetron) all improved compared to the historical control group (89 vs. 82% (p< 0.0001), 96 vs 95% (not significant) and 90 vs 82% (p<0.0001)) while decreasing unwarranted prescription for PONV prophylaxis (10 vs. 13 %). In the pre-operative screening clinic, the main reason for not prescribing PONV prophylaxis was disagreement with the risk estimate by the decision support system. In the OR/PACU, the main reasons for not administering PONV prophylaxis were: 'unintended non-adherence' and 'failure to document'. In this study requesting a reason for non-adherence is associated with improved guideline adherence. The effect seems to depend on the underlying reason for non-adherence. It also illustrates the importance of human factors principles in the design of decision support. Some reasons for non-adherence may not be influenced by automated reminders.


Comparison of Icare Pro Tonometry and Icare One Tonometry Measurements in Healthy Eyes
To compare intraocular pressure (IOP) measurements obtained with the Icare Pro tonometer used in clinical practice and the Icare One self-tonometer. Fifty-two eyes of 52 healthy, right-handed individuals with no prior intraocular surgery or ocular trauma, structural ocular pathology, or systemic disease were evaluated. IOP was first measured using the Icare Pro tonometer. The participants were then told how to use the Icare One tonometer and asked to measure their own IOP. The results were analyzed statistically using SPSS v.24. Of the 52 healthy participants, 16 (30.7%) were male and 36 (69.3%) were female. Their mean age was 31.6±6.3 (23-47) years. Mean IOP measured with the Icare Pro was 17.10±6.2 (11.5-25.2) mmHg, and the mean self-measured IOP with Icare One was 14.01±3.4 (7-24) mmHg. When the two methods were compared using Levene's t-test, there was a significant mean difference of -3.08±0.6 (95% confidence interval: -4.39 -1.78; p<0.001). In this study, there was a significant difference between the IOP measurements we made using the Icare Pro and the participants' self-measured IOP using the Icare One, with the latter being relatively lower. This may be related to the fact that the participants were unfamiliar with using the Icare One. Although the Icare One is a promising tool for glaucoma patients to self-monitor their IOP, further studies are needed.


Properties of synaptic vesicle pools in mature central nerve terminals.
Readily releasable and reserve pools of synaptic vesicles play different roles in neurotransmission, and it is important to understand their recycling and interchange in mature central synapses. Using adult rat cerebrocortical synaptosomes, we have shown that 100 mosm hypertonic sucrose caused complete exocytosis of only the readily releasable pool (RRP) of synaptic vesicles containing glutamate or gamma-aminobutyric acid. Repetitive hypertonic stimulations revealed that this pool recycled (and reloaded the neurotransmitter from the cytosol) fully in <30 s and did so independently of the reserve pool. Multiple rounds of exocytosis could occur in the constant absence of extracellular Ca(2+). However, although each vesicle cycle includes a Ca(2+)-independent exocytotic step, some other stage(s) critically require an elevation of cytosolic [Ca(2+)], and this is supplied by intracellular stores. Repetitive recycling also requires energy, but not the activity of phosphatidylinositol 4-kinase, which maintains the normal level of phosphoinositides. By varying the length of hypertonic stimulations, we found that approximately 70% of the RRP vesicles fused completely with the plasmalemma during exocytosis and could then enter silent pools, probably outside active zones. The rest of the RRP vesicles underwent very fast local recycling (possibly by kiss-and-run) and did not leave active zones. Forcing the fully fused RRP vesicles into the silent pool enabled us to measure the transfer of reserve vesicles to the RRP and to show that this process requires intact phosphatidylinositol 4-kinase and actin microfilaments. Our findings also demonstrate that respective vesicle pools have similar characteristics and requirements in excitatory and inhibitory nerve terminals.


The Use of Flexible Ultrasound Transducers for the Detection of Laser-Induced Guided Waves on Curved Surfaces at Elevated Temperatures.
In this study, a flexible ultrasonic transducer (FUT) was applied in a laser ultrasonic technique (LUT) for non-destructive characterization of metallic pipes at high temperatures of up to 176 °C. Compared with normal ultrasound transducers, a FUT is a piezoelectric film made of a PZT/PZT sol-gel composite which has advantages due to its high sensitivity, curved surface adaptability and high temperature durability. By operating a pulsed laser in B-scan mode along with the integration of FUT and LUT, a multi-mode dispersion spectrum of a stainless steel pipe at high temperature can be measured. In addition, dynamic wave propagation behaviors are experimentally visualized with two dimensional scanning. The images directly interpret the reflections from the interior defects and also can locate their positions. This hybrid technique shows great potential for non-destructive evaluation of structures with complex geometry, especially in high temperature environments.


Transcription-Replication Conflict Shapes DNA Break Dynamics.
Double strand breaks (DSBs) originating from transcription and replication conflict (TRC) sites are prone to rearrangements. Through the application of a capture-ligation assay on mouse neural progenitor cells experiencing replication stress, we unveiled that interactions between transcription and replication fork architecture dictate DSB location and orientation. Specifically, telomere-to-centromere forks generate telomere-connected DSBs, while centromere-to-telomere forks lead to centromere-connected DSBs in genomes that replicate during median and late stages. This pattern, however, reverses in early-replicating DNA. Mapping nascent RNA and RNA polymerase activity revealed that head-to-head interactions between replication and transcription machineries elevate DSBs by 30% compared to co-directional interactions. By deleting promoter elements in the moderately transcribed Ctnna2 and Nrxn1 genes, we demonstrated that the removal of transcription suppressed DSB. However, titration of expression at the Ptn locus demonstrated that transcription level alone was insufficient to induce DSB. Our findings underscore how transcription and replication directionality impact genome structural stability.


Phase transitions of CdS microcrystals under high pressure.
The experiment under high pressure using a diamond anvil cell (DAC) requires the utilization of synchrotron radiation. High-pressure experiments were performed using a DAC on CdS microcrystals, both in the far-IR and in the X-ray regions, in order to study the lattice dynamics and lattice stability concerned with the phase transitions. From these experiments, experimental evidence is presented indicating that a CdS microcrystal of smaller diameter shows a higher transition pressure for lattice transformation under pressure. The origin of such an increase in the transition pressure in the microcrystals is discussed in relation to the surface tension.


Concussion Assessment With Smartglasses: Validation Study of Balance Measurement Toward a Lightweight, Multimodal, Field-Ready Platform.
Lightweight and portable devices that objectively measure concussion-related impairments could improve injury detection and critical decision-making in contact sports and the military, where brain injuries commonly occur but remain underreported. Current standard assessments often rely heavily on subjective methods such as symptom self-reporting. Head-mounted wearables, such as smartglasses, provide an emerging platform for consideration that could deliver the range of assessments necessary to develop a rapid and objective screen for brain injury. Standing balance assessment, one parameter that may inform a concussion diagnosis, could theoretically be performed quantitatively using current off-the-shelf smartglasses with an internal accelerometer. However, the validity of balance measurement using smartglasses has not been investigated. This study aimed to perform preliminary validation of a smartglasses-based balance accelerometer measure (BAM) compared with the well-described and characterized waist-based BAM. Forty-two healthy individuals (26 male, 16 female; mean age 23.8 [SD 5.2] years) participated in the study. Following the BAM protocol, each subject performed 2 trials of 6 balance stances while accelerometer and gyroscope data were recorded from smartglasses (Glass Explorer Edition). Test-retest reliability and correlation were determined relative to waist-based BAM as used in the National Institutes of Health's Standing Balance Toolbox. Balance measurements obtained using a head-mounted wearable were highly correlated with those obtained through a waist-mounted accelerometer (Spearman rho, ρ=.85). Test-retest reliability was high (intraclass correlation coefficient, ICC2,1=0.85, 95% CI 0.81-0.88) and in good agreement with waist balance measurements (ICC2,1=0.84, 95% CI 0.80-0.88). Considering the normalized path length magnitude across all 3 axes improved interdevice correlation (ρ=.90) while maintaining test-retest reliability (ICC2,1=0.87, 95% CI 0.83-0.90). All subjects successfully completed the study, demonstrating the feasibility of using a head-mounted wearable to assess balance in a healthy population. Balance measurements derived from the smartglasses-based accelerometer were consistent with those obtained using a waist-mounted accelerometer. Additional research is necessary to determine to what extent smartglasses-based accelerometry measures can detect balance dysfunction associated with concussion. However, given the potential for smartglasses to perform additional concussion-related assessments in an integrated, wearable platform, continued development and validation of a smartglasses-based balance assessment is warranted. This approach could lead to a wearable platform for real-time assessment of concussion-related impairments that could be further augmented with telemedicine capabilities to integrate professional clinical guidance. Smartglasses may be superior to fully immersive virtual reality headsets for this application, given their lighter weight and reduced likelihood of potential safety concerns.


Glucose penetration and fluid transport through coronal root structure and filled root canals.
To measure glucose penetration and fluid transport through coronal root structure and compare it with leakage along the coronal region of root fillings. A total of 50 single-rooted teeth were selected and divided into three groups. Ten roots were sectioned longitudinally and the apical portion was removed leaving a total length of 9 mm. These 20 half-roots served as group 1: root structure (n = 20). The canals of the remaining 40 roots were prepared to size 50 and filled with vertically compacted injectable filling material and sealer. Group 2: Resilon + Epiphany (n = 20) and group 3: gutta-percha + AH26 (n = 20). The apical portion of the root was removed. Glucose penetration through the coronal root structure and coronal root fillings was checked over a period of 4 weeks and fluid transport was measured after completion of the glucose penetration test. Differences between the groups were statistically analysed with the Kruskal-Wallis test and the Mann-Whitney test. The three groups presented significantly different glucose penetration (P < 0.05). The two groups of filled canals showed significant glucose leakage whilst the root structure group did not show any leakage. In the fluid transport model, the root structure group also did not show any leakage. No significant difference in leakage existed between the two vertically compacted filling materials, Resilon with Epiphany sealer and gutta-percha with AH26 in both models (P > 0.05). Under the conditions of this study, in both models used, no leakage was observed through root structure. Filled canals were associated with penetration of glucose regardless of the material used.


Effect of Soft Braces on Pain and Physical Function in Patients With Knee Osteoarthritis: Systematic Review With Meta-Analyses.
To systematically review and synthesize the effects of soft braces on pain and on self-reported and performance-based physical function in patients with knee osteoarthritis. The following electronic databases were searched from inception to April 20, 2016: The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, CINAHL, SPORTDiscus, Web of Science, and PEDro. Randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs), such as controlled clinical trials, crossover studies, and case-control studies, were included. Two reviewers independently screened articles and determined inclusion through predefined criteria. Data related to participant demographics, study design and methods, interventions, and outcomes, including numerical means and SDs, were extracted by 1 reviewer. Methodological quality assessment was independently performed by 2 reviewers. Eleven studies were identified, including 6 RCTs and 5 non-RCTs. The methodological quality of included RCTs was low. There was a moderate improvement in pain (standardized mean difference [SMD]=.52; 95% confidence interval [CI], .14-.89; P=.007; 284 participants) in favor of wearing a brace compared with not wearing a brace for the immediate, within-group comparison. There was a moderate improvement in pain (SMD=.61; 95% CI, .33-.89; P<.001; 206 participants) and a small to moderate improvement in self-reported physical function (SMD=.39; 95% CI, .11-.67; P=.006; 206 participants) in favor of patients receiving a soft brace versus standard care for the prolonged effect, between-group comparison. Currently available evidence indicates that soft braces have moderate effects on pain and small to moderate effects on self-reported physical function in knee osteoarthritis. These findings highlight the importance of soft braces as a technique to improve pain and physical function in both the short- and long-term. Additional high-quality studies are warranted to improve confidence in the findings.


Distribution of aflatoxins in some samples of peanuts.
Naturally occurring G aflatoxins were found at approximately 20 times the level of B aflatoxins in one lot of roasted, blanched peanuts. Official methods, as well as high-pressure liquid chromatography, were used to confirm this finding. Additional routine sample analysis data of raw and roasted peanuts revealed that this finding is not so unusual formerly thought. It was found that 9.8% of the raw peanut samples contained higher levels of G than B aflatoxin; 4.9% containing 2-8 times more G than B aflatoxins. In a smaller sampling of roasted peanuts, 28% of the contaminated peanuts contained more G than B aflatoxins.


Retail food environments research in Canada: A scoping review.
The field of retail food environments research is relatively new in Canada. The objective of this scoping review is to provide an overview of retail food environments research conducted before July 2015 in Canada. Specifically, this review describes research foci and key findings, identifies knowledge gaps and suggests future directions for research. A search of published literature concerning Canadian investigations of retail food environment settings (food stores, restaurants) was conducted in July 2015 using PubMed, Web of Science, Scopus, PsychInfo and ERIC. Studies published in English that reported qualitative or quantitative data on any aspect of the retail food environment were included, as were conceptual papers and commentaries. Eighty-eight studies were included in this review and suggest that the field of retail food environments research is rapidly expanding in Canada. While only 1 paper was published before 2005, 66 papers were published between 2010 and 2015. Canadian food environments research typically assessed either the socio-economic patterning of food environments (n = 28) or associations between retail food environments and diet, anthropometric or health outcomes (n = 33). Other papers profiled methodological research, qualitative studies, intervention research and critical commentaries (n = 27). Key gaps in the current literature include measurement inconsistency among studies and a lack of longitudinal and intervention studies. Retail food environments are a growing topic of research, policy and program development in Canada. Consistent methods (where appropriate), longitudinal and intervention research, and close partnerships between researchers and key stakeholders would greatly advance the field of retail food environments research in Canada.


Simple kinetic Monte Carlo models for dissolution pitting induced by crystal defects.
The solid-on-solid kinetic Monte Carlo model of Lasaga and Blum [Geochim. Cosmochim. Acta 50, 2363 (1986)] for dislocation-controlled etch-pit growth has been extended to the growth of etch pits under the control of multiple dislocations and point defects. This required the development of algorithms that are O(10(3))-O(10(4)) times faster than primitive kinetic Monte Carlo models for surfaces with areas in the range of 1024 x 1024-4096 x 4096 lattice sites. Simulations with multiple line defects indicate that the surface morphology coarsens with increasing time and that the coarsening is more pronounced for large bond-breaking activation energies. For small bond breaking activation energies dissolution enhanced by line defects perpendicular to the dissolving surface results in pits with steep sides terminated by deep narrow hollow tubes (nanopipes). Larger bond breaking activation energies lead to shallow pits without deep nanopipes, and if the bond breaking activation energy is large enough, step flow is the primary dissolution mechanism, and pit formation is suppressed. Simplified models that neglect the far field strain energy density but include either a rapidly dissolving core or an initially empty core lead to results that are qualitatively similar to those obtained using models that include the effects of the far field stress and strain. Simulations with a regular array of line defects show that microscopic random thermal fluctuations play an important role in the coarsening process.


68Ga-PSMA PET/CT Detects the Location and Extent of Primary Prostate Cancer.
We evaluated the accuracy of PET/CT with 68Ga-PSMA-HBED-CC-a 68Ga-conjugated ligand of human prostate-specific membrane antigen (PSMA)-to localize cancer in the prostate and surrounding tissue at initial diagnosis. Twenty-one patients with biopsy-proven prostate cancer underwent 68Ga-PSMA-HBED-CC (68Ga-PSMA) PET/CT at a median of 4 d (range, 0-47 d) before radical prostatectomy. Based on a 6-segment model, the Gleason score and proportion of tumor tissue within each segment (segmental tumor burden, or STB) as determined by histopathology (STBHP) were correlated with SUVmax and STB as determined by different SUV cutoffs for 68Ga-PSMA PET (STBPET1-6). Furthermore, the involvement of seminal vesicles and other extracapsular extension were assessed by histopathology and PET/CT. Histopathology-positive segments (n = 100 of 126; 79%) demonstrated a significantly higher mean ± SD SUVmax (11.8 ± 7.6) than histopathology-negative segments (4.9 ± 2.9; P < 0.001). Receiver-operating-characteristic analysis revealed an optimal SUVmax cutoff of 6.5 for discrimination of histopathology-positive segments from histopathology-negative segments (area under the curve, 0.84; P < 0.001), which gave 67% sensitivity, 92% specificity, a 97% positive predictive value, a 42% negative predictive value, and 72% accuracy. STBPET3 as determined by (2 × blood SUV) + (2 × SD) correlated best with STBHP (Pearson ρ = 0.68; P < 0.001; mean difference ± SD, 19% ± 15%). PET/CT correctly detected invasion of seminal vesicles (n = 11 of 21 patients; 52%) with 86% accuracy and tumor spread through the capsule (n = 12; 57%) with 71% accuracy. 68Ga-PSMA PET/CT accurately detected the location and extent of primary prostate cancer. Our preliminary findings warrant further investigation of 68Ga-PSMA PET/CT in conjunction with needle biopsy.


Multiplexity-facilitated cascades in networks.
Elements of networks interact in many ways, so modeling them with graphs requires multiple types of edges (or network layers). Here we show that such multiplex networks are generically more vulnerable to global cascades than simplex networks. We generalize the threshold cascade model [Watts, Proc. Natl. Acad. Sci. USA 99, 5766 (2002)] to multiplex networks, in which a node activates if a sufficiently large fraction of neighbors in any layer are active. We show that both combining layers (i.e., realizing other interactions play a role) and splitting a network into layers (i.e., recognizing distinct kinds of interactions) facilitate cascades. Notably, layers unsusceptible to global cascades can cooperatively achieve them if coupled. On one hand, this suggests fundamental limitations on predicting cascades without full knowledge of a system's multiplexity; on the other hand, it offers feasible means to control cascades by introducing or removing sparse layers in an existing network.


The traumatic bone cyst.
A case is reported of traumatic cyst lying in the molar region of the mandible. It extended to the inferior border of the mandible and extended the buccal alveolar bone. The cystic cavity contained the inferior neuro-vascular bundle yellow serous fluid, and a small amount of gas. The wall of the cavity was lined with loosely arranged connective tissue with numerous capillaries. Healing was uneventful and clinical and radiographic examinations revealed restoration of bone structure and normal contours.


High tissue eosinophilia as a marker to predict recurrence for eosinophilic chronic rhinosinusitis: a systematic review and meta-analysis.
Patients with eosinophilic chronic rhinosinusitis (ECRS) have been shown to have greater disease severity and poorer treatment outcomes after sinus surgery. Although the inflammatory pattern of ECRS is essential to diagnosing this subtype, there is currently no consensus for diagnosis. Our aim in this study was to determine whether high tissue eosinophilia (HTE), measured as eosinophils per high-power field (eos/HPF), could be used to define ECRS based on likelihood of recurrence. Embase, Medline, and PubMed databases were searched for studies that reported HTE and recurrence in ECRS patients after surgical treatment. We used a random-effects bivariate meta-analysis to calculate summary sensitivity, specificity, and diagnostic odds ratios (DORs) for detecting ECRS at different HTE cut-off scores using risk of recurrence as the primary outcome. We identified 11 articles (n = 3183) that reported HTE associated with recurrence. A cut-off value of >55 eos/HPF showed the highest sensitivity (0.87; 95% confidence interval [CI], 0.82-0.91), specificity (0.97; 95% CI, 0.93-0.99), and DOR (232.7; 95% CI, 91.0-595.1). Meta-regression analysis performed showed that the Quality Assessment of Diagnostic Accuracy Studies score (p = 0.1287), geographic location (p = 0.3745), follow-up time (p = 0.2879), and study design (p = 0.1865) did not affect the test accuracy. Our findings suggest that using eos/HPF has good diagnostic accuracy and may be a useful tool for identifying ECRS patients. Based on the results of our meta-analysis, we recommend a cut-off value of >55 eos/HPF for predicting the likelihood of recurrence of ECRS.


COMET: a new end-station at SOLEIL for coherent magnetic scattering in transmission.
A new instrument named COMET for COherent Magnetic scattering Experiments in Transmission using polarized soft X-rays has been designed and built. This high-vacuum setup is placed at the intermediate focal point of the elastic branch of the SEXTANTS beamline at Synchrotron SOLEIL. The main application is in solid state physics, the instrument being optimized for studying material properties using coherent scattering of soft X-rays with an emphasis on imaging, with chemical selectivity, the magnetic domains of artificially nano-structured materials. The instrument's principal features are presented and illustrated through recently performed experiments.


Cigarette use among high school students--United States, 1991-2007.
Cigarette use is the leading preventable cause of death in the United States. A national health objective for 2010 is to reduce the prevalence of current cigarette use among high school students to 16% or less (27-2b). To examine changes in cigarette use among high school students in the United States during 1991-2007, CDC analyzed data from the national Youth Risk Behavior Survey (YRBS). This report summarizes the results of that analysis, which indicated that the prevalence of lifetime cigarette use was stable during 1991-1999 and then declined from 70.4% in 1999 to 50.3% in 2007. The prevalence of current cigarette use increased from 27.5% in 1991 to 36.4% in 1997, declined to 21.9% in 2003, and remained stable from 2003 to 2007. The prevalence of current frequent cigarette use increased from 12.7% in 1991 to 16.8% in 1999 and then declined to 8.1% in 2007. To resume the declines observed in current cigarette use during 1997-2003 and achieve the 2010 objective, communitywide comprehensive tobacco-control programs that use coordinated evidence-based strategies should be implemented and revitalized.


Hypertension in elderly persons.
To provide an overview of the prevalence of hypertension in the elderly population and discuss the advantages and disadvantages of various classes of antihypertensive drugs. We review the published clinical trials on treatment of elderly patients with hypertension and describe adverse reactions that are frequently associated with antihypertensive therapy. On the basis of the standard for control of hypertension established by the National Health and Nutrition Examination Survey for 1988-1991 (140/90 mm Hg), almost 75% of all African-Americans and 50% of all whites 60 to 74 years of age have hypertension. If modifications in lifestyle (such as weight reduction and increase in exercise) do not normalize blood pressure levels, drug therapy is warranted. Meta-analyses of major trials of treatment of hypertension have revealed significant reductions in cardiovascular-related mortality and stroke, and available data indicate that prudent use of antihypertensive agents is associated with an acceptable degree of toxicity. Low-dose thiazide diuretics and b-blockers remain the agents of choice. Several trials have substantiated the effectiveness of treatment of hypertension in elderly subjects. Drug therapy should be initiated at low doses, and careful follow-up should monitor for adverse effects.


Silicon Carbide Converters and MEMS Devices for High-temperature Power Electronics: A Critical Review.
The significant advance of power electronics in today's market is calling for high-performance power conversion systems and MEMS devices that can operate reliably in harsh environments, such as high working temperature. Silicon-carbide (SiC) power electronic devices are featured by the high junction temperature, low power losses, and excellent thermal stability, and thus are attractive to converters and MEMS devices applied in a high-temperature environment. This paper conducts an overview of high-temperature power electronics, with a focus on high-temperature converters and MEMS devices. The critical components, namely SiC power devices and modules, gate drives, and passive components, are introduced and comparatively analyzed regarding composition material, physical structure, and packaging technology. Then, the research and development directions of SiC-based high-temperature converters in the fields of motor drives, rectifier units, DC-DC converters are discussed, as well as MEMS devices. Finally, the existing technical challenges facing high-temperature power electronics are identified, including gate drives, current measurement, parameters matching between each component, and packaging technology.


Electrochemical deoxygenative homo-couplings of aromatic aldehydes.
An electrochemical deoxygenative homo-coupling of aromatic aldehydes is achieved to selectively access bibenzyl and stilbene derivatives. The protocol allows the homo-coupling of aldehydes to occur after single-electron-reduction at the cathode. Taking advantage of the oxophilicity of triphenylphosphine, the electrochemical deoxygenation proceeds smoothly to give reductive homo-coupling products.


Arthroscopic treatment options for irreparable rotator cuff tears of the shoulder.
The management of patients with irreparable rotator cuff tears remains a challenge for orthopaedic surgeons with the final treatment option in many algorithms being either a reverse shoulder arthroplasty or a tendon transfer. The long term results of these procedures are however still widely debated, especially in younger patients. A variety of arthroscopic treatment options have been proposed for patients with an irreparable rotator cuff tear without the presence of arthritis of the glenohumeral joint. These include a simple debridement with or without a biceps tenotomy, partial rotator cuff repair with or without an interval slide, tuberplasty, graft interposition of the rotator cuff, suprascapular nerve ablation, superior capsule reconstruction and insertion of a biodegradable spacer (Inspace) to depress the humeral head. These options should be considered as part of the treatment algorithm in patients with an irreparable rotator cuff and could be used as either as an interim procedure, delaying the need for more invasive surgery in the physiologically young and active, or as potential definitive procedures in the medically unfit. The aim of this review is to highlight and summarise arthroscopic procedures and the results thereof currently utilised in the management of these challenging patients.


Per- and polyfluoroalkyl substances in paired dust and carpets from childcare centers.
Carpets can be a significant source of per- and polyfluoroalkyl substances (PFASs) in the indoor environment and may be an especially important source of exposure for children and toddlers. Most previous studies focused on measuring indoor dust only. In this study, we measured PFAS concentrations in paired carpet and dust samples from 18 California childcare centers in 2018 to investigate carpet as a contributor to PFASs in dust. Median total PFAS concentrations (∑PFASs) in carpets and dust were 471 ng/g and 523 ng/g, respectively. 6:2 FTOH and 6:2 FTSA were the two dominant PFASs, collectively accounting for over 50% of the ∑PFASs in both media. Other frequently detected PFASs included C4-C14 perfluoroalkylcarboxylic acids, C4-C8 perfluoroalkylsulfonic acids, PFDS, 4:2 FTSA, 8:2 FTSA, FOSA, MeFOSE, EtFOSE, 8:2 FTOH, and 10:2 FTOH. We found strong associations between PFAS levels in carpet and dust pairs, suggesting that carpets can be a source and a sink for PFASs. The estimated total perfluoroalkyl acids (PFAA) intake via dust ingestion for children was 0.023, 0.096, and 1.9 ng/kg body weight/day in the low-, intermediate-, and high-exposure scenarios, respectively. Our data suggest that PFASs of emerging concern are playing an increasingly important role in indoor exposure to PFASs.


Detection of HBsAg and HBsAb in sweat.
HBsAg was detected in the sweat of 9/18 seropositive, but 0/20 seronegative probands. Frequency of detection correlated to serum titer of HBsAg, blood contamination and efficiency of sweat concentrating. On base of quantitative evaluations it is assumed, that blood and/or plasma contaminations are responsible for the presence of HBsAg in sweat. Since HBsAg and hepatitis virus B are of similar diameter, this mechanisms should work on the infectious agent too. Thus HBsAg could prove a marker, to calculate the infectivity of sweat in comparison to the corresponding serum specimen (10(-6) to 10(-7). HBsAb was detected in sweat too and was confined to HBsAb-seropositive probands (4/5). It is discussed, that the presence of HBsAb in sweat could provide protection against reinfections by contact and thus contribute to homologous immunity in hepatitis B.


A time-insensitive predictive instrument for acute hospital mortality due to congestive heart failure: development, testing, and use for comparing hospitals: a multicenter study.
The purpose of this study was to develop a "time-insensitive" predictive instrument (TIPI) for acute hospital mortality due to congestive heart failure. In Phase 1, based on prospectively collected data on 401 congestive heart failure patients among 5,773 study patients who presented to six New England hospitals over a 2-year period whose chief complaints were chest pain, shortness of breath, or other cardiac symptoms, a multivariable logistic regression was used to develop the TIPI for acute mortality. Discrimination between patients who lived and those who died was reflected by receiver-operating characteristic (ROC) curve area of 0.90. Predicted mortality was found to not vary significantly from actual mortality rates across deciles of predicted probabilities from 0% to 100%. In Phase 2, the six hospitals' actual mortality rates for their congestive heart failure patients were compared to their respective rates predicted by the TIPI. Actual hospital mortality rates ranged from 3.6% to 11.3%, with no hospital having a statistically significantly higher rate. Predicted mortality rates ranged from 4% to 9%, with one hospital having a significantly lower predicted rate (P = .01), and one hospital having a borderline significantly higher predicted rate (P = .07). Individual hospitals' differences between actual and predicted mortality ranged from -3.8% to +4.7% (all NS). When grouped by hospital type, respectively for urban teaching, smaller city teaching, and rural non-teaching hospitals, the actual mortality rates were 5.1%, 10.5%, and 5.4%, (NS). The predicted mortality rates were 8.3%, 6.1%, and 5.4%, respectively, with the rate for urban major teaching centers being significantly higher (P = .03). No hospital type had significant differences between their actual and predicted mortality rates (NS). This congestive heart failure mortality TIPI (CHFM-TIPI) shows potential for risk-adjusted studies of hospitals, mortality for multi-hospital groups, hospital-to-hospital comparisons, and potentially for within-hospital assessment and if further validated, potentially also for real-time clinical use.


Ab initio study of small graphitic cones with triangle, square, and pentagon apex.
Accurate geometries of carbon nanocones of different sizes with a triangle, square or pentagon at the apex have been determined for the first time using a quantum chemical optimization method. The structure close to the apex is distorted from an ideal conical surface. The charging effect of the central defect is quite different from that predicted by tight-binding calculations. The symmetry behavior of the frontier orbitals and the size of the highest occupied molecular orbital-lowest unoccupied molecular orbital gap versus cone type and size is explained. The density of states quickly converges towards that of graphite when the size of the cone increases. In comparison to previous results in the literature it is found that the local densities of states of cones, that are locally different but belong to the same topo-combinatoric class, share common features.


Neuropsychiatric lupus.
Neuropsychiatric abnormalities in patients with systemic lupus have been recognized for more than a century. Although the prognosis of lupus has improved, involvement of the nervous system continues to be a major feature, with some abnormality recognized in 50 to 66 per cent of lupus patients. Diagnosis and therapy of neurologic disease remain the most difficult clinical challenges in the management of SLE.


Habituation of glomerular responses in the olfactory bulb following prolonged odor stimulation reflects reduced peripheral input.
Following prolonged odor stimulation, output from olfactory bulb (OB) mitral/tufted (M/T) cells is decreased in response to subsequent olfactory stimulation. Currently, it is unclear if this decrease is a function of adaptation of peripheral olfactory sensory neuron (OSN) responses or reflects depression of bulb circuits. We used wide-field calcium imaging in anesthetized transgenic GCaMP2 mice to compare excitatory glomerular layer odor responses before and after a 30-s odor stimulation. Significant habituation of subsequent glomerular odor responses to both the same and structurally similar odorants was detected with our protocol. To test whether depression of OSN terminals contributed to this habituation, olfactory nerve layer (ON) stimulation was used to drive glomerular layer responses in the absence of peripheral odor activation of the OSNs. Following odor habituation, in contrast to odor-evoked glomerular responses, ON stimulation-evoked glomerular responses were not habituated. The difference in response between odor and electrical stimulation following odor habituation provides evidence that odor response reductions measured in the glomerular layer of the OB are most likely the result of OSN adaptation processes taking place in the periphery.


The relationship between distal trunk morphology and object grasping in the African savannah elephant (Loxodonta africana).
During reach-to-grasp movements, the human hand is preshaped depending on the properties of the object. Preshaping may result from learning, morphology, or motor control variability and can confer a selective advantage on that individual or species. This preshaping ability is known in several mammals (i.e., primates, carnivores and rodents). However, apart from the tongue preshaping of lizards and chameleons, little is known about preshaping of other grasping appendages. In particular, the elephant trunk, a muscular hydrostat, has impressive grasping skills and thus is commonly called a hand. Data on elephant trunk grasping strategies are scarce, and nothing is known about whether elephants preshape their trunk tip according to the properties of their food. To determine the influence of food sizes and shapes on the form of the trunk tip, we investigated the morphology of the distal part of the trunk during grasping movements. The influence of food item form on trunk tip shape was quantified in six female African savannah elephants (Loxodonta africana). Three food item types were presented to the elephants (elongated, flat, and cubic), as well as three different sizes of cubic items. A total of 107 ± 10 grips per individual were video recorded, and the related trunk tip shapes were recorded with a 2D geometric morphometric approach. Half of the individuals adjusted the shape of the distal part of their trunk according to the object type. Of the three elephants that did not preshape their trunk tip, one was blind and another was subadult. We found that elephants preshaped their trunk tip, similar to the preshaping of other species' hands or paws during reach-to-grasp movements. This preshaping may be influenced by visual feedback and individual learning. To confirm these results, this study could be replicated with a larger sample of elephants.


Development of a 5-plex SILAC method tuned for the quantitation of tyrosine phosphorylation dynamics.
The propagation of phosphorylation downstream of receptor tyrosine kinases is a key dynamic cellular event involved in signal transduction, which is often deregulated in disease states such as cancer. Probing phosphorylation dynamics is therefore crucial for understanding receptor tyrosine kinases' function and finding ways to inhibit their effects. MS methods combined with metabolic labeling such as stable isotope labeling with amino acids in cell culture (SILAC) have already proven successful in deciphering temporal phosphotyrosine perturbations. However, they are limited in terms of multiplexing, and they also are time consuming, because several experiments need to be performed separately. Here, we introduce an innovative approach based on 5-plex SILAC that allows monitoring of phosphotyrosine signaling perturbations induced by a drug treatment in one single experiment. Using this new labeling strategy specifically tailored for phosphotyrosines, it was possible to generate the time profiles for 318 unique phosphopeptides belonging to 215 proteins from an erlotinib-treated breast cancer cell line model. Hierarchical clustering of the time profiles followed by pathway enrichment analysis highlighted epidermal growth factor receptor (EGFR or ErbB1) and ErbB2 signaling as the major pathways affected by erlotinib, thereby validating the method. Moreover, based on the similarity of its time profile to those of other proteins in the ErbB pathways, the phosphorylation at Tyr453 of protein FAM59A, a recently described adaptor of EGFR, was confirmed as tightly involved in the signaling cascade. The present investigation also demonstrates the remote effect of EGFR inhibition on ErbB3 phosphorylation sites such as Tyr1289 and Tyr1328, as well as a potential feedback effect on Tyr877 of ErbB2. Overall, the 5-plex SILAC is a straightforward approach that extends sample multiplexing and builds up the arsenal of methods for tyrosine phosphorylation dynamics.


Normal platelet adhesiveness and aggregation in congenital PTA or Hageman factor deficiency.
Platelet adhesiveness and aggregation were studied in two patients with congenital factor XI deficiency and in a patient with congenital factor XII deficiency. A normal aggregation pattern was observed in every instance, regardless of the aggregating agent. The same was true for platelet adhesiveness. It is concluded that factor XI and factor XII play no role in platelet aggregation and adhesiveness.


Indications and Outcomes From 32 Consecutive Patients for the Treatment of Rectal Lesions by Transanal Minimally Invasive Surgery.
The aim of this study was to evaluate the feasibility, safety, perioperative morbidity, and short-term outcomes of the transanal minimally invasive surgery (TAMIS) technique. This is a descriptive review of prospectively collected data from 32 consecutive patients who underwent TAMIS procedures in our colorectal unit over a 40-month period. GelPOINT Path port was used in all cases. Demographic data, indications, tumor characteristics, morbidity, and follow-up data were collected. Primary endpoints included feasibility, safety, perioperative morbidity, and resection quality. Fifteen adenomas, 12 carcinomas, 1 gastrointestinal stromal tumor, and 1 neuroendocrine tumor were locally excised. Additionally, 3 pelvic abscesses were drained transanally using the TAMIS port. Mean distance from the anal verge was 5.6 ± 1.5 cm. Early postoperative complications occurred in 22%, with only one case of major complication (3.1%) requiring reoperation, and no postoperative mortality. Four carcinomas were understaged (33.3%) and 1 adenoma overstaged (6.7%) preoperatively. Three carcinomas were not suspected preoperatively (25%). Microscopic positive lateral margin was found in one case, and no affected deep margin was found. Fragmentation rate was 6.9%, 2 cases, both lesions over 20 cm2. In cases of fit patients with high-risk carcinomas, 2 underwent immediate salvage surgery and another 2 refused and were treated with adjuvant radiotherapy. With a median follow-up of 26 months, the overall recurrence rate was 10.3%, 1 adenoma and 2 carcinomas. TAMIS seems to be a safe and reproducible procedure for local excision of well-selected rectal lesions with low morbidity and good functional outcomes.


Rumen and cecum bacteria of beef cattle that differ in feed efficiency fed a forage diet.
Most of the research addressing feed efficiency and the microbiota has been conducted in cattle fed grain diets, although cattle evolved to consume forage diets. Our hypothesis was that the bacteria in the rumen and cecum differed in cattle that have a common feed intake but had different ^average daily body weight gains (ADG) on a forage diet. Heifers (n = 134) were 606 ± 1 d of age and weighed 476 ± 3 kg at the start of the 84-d feeding study. Heifers were offered ad libitum access to a totally mixed ration that consisted of 86% ground brome hay, 10% wet distillers grains with solubles, and 4% mineral supplement as dry matter. Feed intake and body weight gain were measured, and gain was calculated. Heifers with the least (n = 8) and greatest (n = 8) ADG within 0.32 SD of the mean daily dry matter intake were selected for sampling. Digesta samples from the rumen and cecum were collected, and subsequent 16S analysis was conducted to identify Amplicon Sequence Variants. There were no differences in Alpha and Beta diversity between ADG classification within sample sites (P > 0.05). Both sample sites contained calculated balances of sister clades using phylogenetic isometric log ratio transferred data that differed across ADG classification. These findings suggest that bacteria did not differ at the community level, but there was structural difference at the clade level.


Nonverbal communication in a Caribbean medical school: "Touch is a touchy issue".
The heath communication curriculum at the Trinidad campus of the University of the West Indies was developed out of practices advocated in large Western countries. Many students and tutors observed that the nonverbal skills advocated in these approaches did not fit the complex cultural dynamics of the Caribbean. A study was developed to understand the problems Caribbean students faced with these nonverbal communication practices. Thirty-six students representing different Caribbean territories were randomly selected from the two compulsory communication skills courses: Communication Skills for Health Personnel and Communication Skills for the Health Professions class list. These students participated in 4 focus group discussions (FGD). The FGD questions were formulated on the nonverbal skills advanced in the Calgary-Cambridge Guide to the doctor-patient interview. The findings supported the view that recommended nonverbal skills were in conflict with expected doctor-patient behavior in different Caribbean territories. Students felt that nonverbal communication needed to be treated with greater cultural sensitivity. These findings stimulated changes to the health communication program. this article identifies changes made to the communication skills program in response to cultural difference.


Low-frequency fluctuations in the Lang-Kobayashi equations.
The Lang-Kobayashi equations are simplified by a local analysis that focuses, in the long-delay-time limit, on one pair of mode-antimode only. In the domain of hysteresis between the two steady states, low frequency fluctuations (LFF) can be observed if there is a domain of bistability where both steady states are unstable. The high-frequency oscillations and the drop-offs in the LFF regime are associated with a dynamics close to the unstable upper and lower branch steady states, respectively.