Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy.

PURPOSE Dose-dense, every-2-week adjuvant chemotherapy using doxorubicin/cyclophosphamide (AC; 60/600 mg/m2 every 2 weeks x four cycles) followed by paclitaxel (175 mg/m2 every 2 weeks x four cycles), requiring filgrastim on days 3 through 10 of each cycle has been shown to improve survival compared with every-3-week treatment schedules but is associated with greater risk of RBC transfusion (13%). The role of long-acting hematopoietic growth factors in facilitating every-2-week chemotherapy and minimizing hematologic toxicity has not been established. PATIENTS AND METHODS Women with stage I to III breast cancer received dose-dense AC --> paclitaxel as neoadjuvant or adjuvant chemotherapy. Patients received pegfilgrastim 6 mg subcutaneous (SQ) on day 2 of each cycle. Darbepoetin alfa was initiated at 200 microg SQ every 2 weeks for hemoglobin < or = 12 g/dL, and administered thereafter, according to a preplanned algorithm. The primary end points were to evaluate the percentage of patients with febrile neutropenia and the percentage of patients requiring RBC transfusion. RESULTS Among 135 women treated on this single arm study, there were two cases of febrile neutropenia (incidence 1.5%). No patients received RBC transfusion. Darbepoetin alfa therapy was initiated in 92% of patients. The modest leukocytosis seen during paclitaxel cycles was attributable, in part, to corticosteroid premedication. Other toxicity and dose-delivery were similar to dose-dense AC --> paclitaxel in Cancer and Leukemia Group B 9741. CONCLUSION Pegfilgrastim and darbepoetin alfa are effective and safe in facilitating every-2-week AC --> paclitaxel, minimizing rates of febrile neutropenia and RBC transfusion.
Application of the Berlin definition in PROMMTT patients: The impact of resuscitation on the incidence of hypoxemia

BACKGROUND Acute lung injury following trauma resuscitation remains a concern despite recent advances. With the use of the PROMMTT study population, the risk of hypoxemia and potential modifiable risk factors are studied. METHODS Patients with survival for 24 hours or greater with at least one intensive care unit day were included in the analysis. Hypoxemia was categorized using the Berlin definition for adult respiratory distress syndrome: none (PaO2-to-FIO2 ratio [P/F] > 300 mm Hg), mild (P/F, 201–300 mm Hg), moderate (P/F, 101–200 mm Hg) or severe (P/F ⩽ 100 mm Hg). The cohort was dichotomized into those with none or mild hypoxemia and those with moderate or severe injury. Early resuscitation was defined as that occurring 0 hour to 6 hours from arrival; late resuscitation was defined as that occurring 7 hours to 24 hours. Multivariate logistic regression models were developed controlling for age, sex, mechanisms of injury, arrival physiology, individual Abbreviated Injury Scale (AIS) scores, blood transfusions, and crystalloid administration. RESULTS Of the patients 58.7% (731 of 1,245) met inclusion criteria. Hypoxemia occurred in 69% (mild, 24%; moderate, 28%; severe, 17%). Mortality was highest (24%) in the severe group. During early resuscitation (0–6 h), logistic regression revealed age (odd ratio [OR], 1.02; 95% confidence interval [CI], 1.00–1.04), chest AIS score (OR, 1.31; 95% CI, 1.10–1.57), and intravenously administered crystalloid fluids given in 500 mL increments (OR, 1.12; 95% CI, 1.01–1.25) as predictive of moderate or severe hypoxemia. During late resuscitation, age (OR, 1.02; 95% CI, 1.00–1.04), chest AIS score (OR, 1.33; 95% CI, 1.11–1.59), and crystalloids given during this period (OR, 1.05; 95% CI, 1.01–1.10) were also predictive of moderate-to-severe hypoxemia. Red blood cell, plasma, and platelet transfusions (whether received during early or late resuscitation) failed to demonstrate an increased risk of developing moderate/severe hypoxemia. CONCLUSION Severe chest injury, increasing age, and crystalloid-based resuscitation, but not blood transfusions, were associated with increased risk of developing moderate-to-severe hypoxemia following injury. LEVEL OF EVIDENCE Epidemiologic/prognostic study, level III.
Symptom Experience of Pulmonary Arterial Hypertension Patients

Purpose: To describe symptoms experienced by pulmonary arterial hypertension (PAH) patients and the impact these symptoms have had on their lives. Method: Qualitative descriptive methodology was chosen incorporating semistructured interviews to investigate the symptom experience of ten patients with PAH. Results: All patients were diagnosed with WHO Group 1 PAH and 70% were WHO functional Class III. Two overarching themes emerged: holding back and redefining life. Holding back was represented by three sub-themes: fear, anticipation of worsening symptoms, and treatment effects. Redefining life was characterized by uncertainty, activity restrictions, and making the best of it. Conclusion: This study revealed specific concerns related to the symptom experience of PAH patients and how they redefined their lives to accommodate these symptoms. These findings provide a basis for larger, quantitative studies to examine the extent of symptom impact as well as a framework for development of self management interventions to improve the symptom experience and QOL.
Mapping hemodynamic correlates of seizures using fMRI: A review

Functional magnetic resonance imaging (fMRI) is able to detect changes in blood oxygenation level associated with neuronal activity throughout the brain. For more than a decade, fMRI alone or in combination with simultaneous EEG recording (EEG‐fMRI) has been used to investigate the hemodynamic changes associated with interictal and ictal epileptic discharges. This is the first literature review to focus on the various fMRI acquisition and data analysis methods applied to map epileptic seizure‐related hemodynamic changes from the first report of an fMRI scan of a seizure to the present day. Two types of data analysis approaches, based on temporal correlation and data driven, are explained and contrasted. The spatial and temporal relationship between the observed hemodynamic changes using fMRI and other non‐invasive and invasive electrophysiological and imaging data is considered. We then describe the role of fMRI in localizing and exploring the networks involved in spontaneous and triggered seizure onset and propagation. We also discuss that fMRI alone and combined with EEG hold great promise in the investigation of seizure‐related hemodynamic changes non‐invasively in humans. We think that this will lead to significant improvements in our understanding of seizures with important consequences for the treatment of epilepsy. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.
Noninvasive Carbon Dioxide Monitoring in a Porcine Model of Acute Lung Injury Due to Smoke Inhalation and Burns

ABSTRACT In critically ill intubated patients, assessment of adequacy of ventilation relies on measuring partial pressure of arterial carbon dioxide (PaCO2), which requires invasive arterial blood gas analysis. Alternative noninvasive technologies include transcutaneous CO2 (tPCO2) and end-tidal CO2 (EtCO2) monitoring. We evaluated accuracy of tPCO2 and EtCO2 monitoring in a porcine model of acute lung injury (ALI) due to smoke inhalation and burns. Eight anesthetized Yorkshire pigs underwent mechanical ventilation, wood-bark smoke inhalation injury, and 40% total body surface area thermal injury. tPCO2 was measured with a SenTec system (SenTec AG, Therwil, Switzerland) and EtCO2 with a Capnostream-20 (Oridion Medical, Jerusalem, Israel). These values were compared with PaCO2 measurements from an arterial blood gas analyzer. Paired measurements of EtCO2-PaCO2 (n = 276) and tPCO2-PaCO2 (n = 250) were recorded in the PaCO2 range of 25 to 85 mmHg. Overlapping data sets were analyzed based on respiratory and hemodynamic status of animals. Acute lung injury was defined as PaO2/FIO2 ⩽ 300 mmHg; hemodynamic instability was defined as mean arterial pressure ⩽ 60 mmHg. Before ALI, EtCO2 demonstrated moderate correlation with PaCO2 (R2 = 0.45; P < 0.0001), which deteriorated after onset of ALI (R2 = 0.12; P < 0.0001). Before ALI, tPCO2 demonstrated moderate correlation (R2 = 0.51, P < 0.0001), which was sustained after onset of ALI (R2 = 0.78; P < 0.0001). During hemodynamic stability, EtCO2 demonstrated moderate correlation with PaCO2 (R2 = 0.44; P < 0.0001). During hemodynamic instability, EtCO2 did not correlate with PaCO2 (R2 = 0.03; P = 0.29). tPCO2 monitoring demonstrated strong correlation with PaCO2 during hemodynamic stability (R2 = 0.80, P < 0.0001), which deteriorated under hemodynamically unstable conditions (R2 = 0.39; P < 0.0001). Noninvasive carbon dioxide monitors are acceptable for monitoring trends in PaCO2 under conditions of hemodynamic and pulmonary stability. Under unstable conditions, reevaluation of patient status and increased caution in the interpretation of results are required.
An economic analysis of farm forestry as a means of controlling dryland salinity

Large areas of agricultural land under conventional crops and pastures are at risk of dryland salinisation in Australia. The salinisation problem can be controlled by strategic and large‐scale planting of trees; however, farm forestry enterprises evaluated with conventional discounting techniques do not generally rank as an attractive alternative to annual crops on productive land. In this article, an optimal control model that explicitly accounts for decline or improvement in land quality over a period of 40 years is presented. The optimal area planted to trees and the optimal groundwater‐table trajectory through time are determined under a variety of scenarios. Implications of the results for policy design are discussed.
Reliability of urinary cytodiagnosis in urothelial neoplasms

A retrospective study was done to explore the reliability of urinary cytologic examination of 117 cases of transitional cell carcinoma seen at this institution for the period 1980 to 1984. A specificity of 99%, sensitivity of 85%, false‐positive rate of 11%, and false‐negative rate of 10% were obtained. A single blind review of cytologic and histologic material from 66 of the cases was also performed for evaluation of the cytologic criteria employed for the grading of tumors. Cytohistologic correlation of grade I lesions was poor, whereas correlation of grades II and III was reasonably good. Carcinoma in situ was cytologically recognized in all instances but was difficult to distinguish from grade III carcinoma. Cancer 56: 2041‐2045, 1985.
Applications of meta-analytic structural equation modelling in health psychology: examples, issues, and recommendations

ABSTRACT Statistical methods play an important role in behavioural, medical, and social sciences. Two recent statistical advances are structural equation modelling (SEM) and meta-analysis. SEM is used to test hypothesised models based on substantive theories, which can be path, confirmatory factor analytic, or full structural equation models. Meta-analysis is used to synthesise research findings in a particular topic. This article demonstrates another recent statistical advance – meta-analytic structural equation modelling (MASEM) – that combines meta-analysis and SEM to synthesise research findings for the purpose of testing hypothesised models. Using the theory of planned behaviour as an example, we show how MASEM can be used to address important research questions that cannot be answered by univariate meta-analyses on Pearson correlations. Specifically, MASEM allows researchers to: (1) test whether the proposed models are consistent with the data; (2) estimate partial effects after controlling for other variables; (3) estimate functions of parameter estimates such as indirect effects; and (4) include latent variables in the models. We illustrate the procedures with an example on the theory of planned behaviour. Practical issues in MASEM and suggested solutions are discussed.
Rescue of expression and signaling of human luteinizing hormone G protein-coupled receptor mutants with an allosterically binding small-molecule agonist

Naturally occurring mutations of G protein-coupled receptors (GPCRs) causing misfolding and failure to traffic to the cell surface can result in disease states. Some small-molecule orthosteric ligands can rescue such misfolded receptors, presumably by facilitating their correct folding and shuttling to the plasma membrane. Here we show that a cell-permeant, allosterically binding small-molecule agonist (Org 42599) rescues the folding and cell surface expression, and therefore target cell signaling, of mutant human luteinizing hormone (LH) receptors (A593P and S616Y) that cause Leydig cell hypoplasia in man. Both mutant receptors were retained in the cytoplasm whereas WT receptor localized at the cell membrane, and binding of LH to cells expressing the mutant receptors was markedly lower than to those expressing the WT receptor. Incubation with Org 42599 increased mutant receptor expression, cell surface localization, and the proportion of mutant receptor in the mature glycosylated form. Importantly, although LH stimulated little (S616Y) or no (A593P) activation of cells expressing mutant receptors, incubation of cells with Org 42599 facilitated rescue of expression and stimulation by the native ligand, LH. Although Org 42599 could activate these receptors, it could not displace 125I-labeled human LH binding to the WT receptor, indicating that it acts in an allosteric manner. Here we demonstrate a small-molecule GPCR allosteric agonist that functionally rescues intracellularly retained mutant LH receptors by facilitating their cell surface expression. This approach may have application for treatment of infertile patients bearing such mutations and, more broadly, for other misfolded GPCR mutants resulting in human pathologic processes.
Abnormal vascular, platelet and coagulation markers in primary thrombocythaemia are not reversed by treatments that reduce the platelet count

Although the primary aim of the treatment of primary thrombocythaemia is to reduce platelet counts, its effect on platelet activation, vascular dysfunction and coagulopathy, which are also abnormal, is unknown. We therefore hypothesised that successful treatment of primary thrombocythaemia is accompanied by an improvement in markers of these processes. To test this hypothesis, we compared 38 patients with 15 healthy age and sex-matched controls. Seven untreated patients had platelet counts higher than those 31 on treatment, that were in turn higher than the 15 controls (all p<0.01). Plasma fibrinogen, P-selectin, von Willebrand factor and sVCAM were higher in both patient groups compared to controls (all p<0.05), but not between patient groups. sE-selectin and sICAM were unaltered between the three groups. D-dimers were higher in treated patients than in controls. We conclude that successful thrombocytosis treatment does not normalise markers of coagulation, platelet, or endothelial pathophysiology. This may account for continuing risk of pathology in those whose platelet counts have been normalised.
A 50-110 GHz ohmic contact RF MEMS silicon switch with high isolation

This paper presents the new concept of RF MEMS silicon contact switch and its verification for high isolation at 50–110 GHz. A high isolation is achieved by locating the floating top contact electrode 30 µm apart from the bottom coplanar waveguide (CPW) signal line in lateral direction at initial off-state. The switch contact is realized by the dual axis movement, namely a lateral movement by comb electrodes and a following vertical movement by a bottom electrode. The actuation voltages are measured for dual axis movement. The isolation of the switch was measured at 50–110 GHz to prove the concept of isolation improvement using dual axis movement.
Deconstructing the Dogma

Since the birth of molecular biology it has been generally assumed that most genetic information is transacted by proteins, and that RNA plays an intermediary role. This led to the subsidiary assumption that the vast tracts of noncoding sequences in the genomes of higher organisms are largely nonfunctional, despite the fact that they are transcribed. These assumptions have since become articles of faith, but they are not necessarily correct. I propose an alternative evolutionary history whereby developmental and cognitive complexity has arisen by constructing sophisticated RNA‐based regulatory networks that interact with generic effector complexes to control gene expression patterns and the epigenetic trajectories of differentiation and development. Environmental information can also be conveyed into this regulatory system via RNA editing, especially in the brain. Moreover, the observations that RNA‐directed epigenetic changes can be inherited raises the intriguing question: has evolution learnt how to learn?
Toward assembly plan from observation - Task recognition with planar, curved and mechanical contacts

The authors have been developing a novel method for programming a robot, called the assembly-plan-from-observation (APO) method. The APO method aims to build a system that has threefold capabilities. It observes a human performing an assembly task, it understands the task based on this observation, and it generates a robot program to achieve the same task. This paper concentrates on the APO's main loop, which is task recognition. Using object recognition results, the task recognition module determines what kind of assembly task is performed. A previous system, recognizes assembly tasks which only handle polyhedral objects. The system reported here handles curved objects and other mechanical contacts as well. The authors define task models for these cases and show that task models are useful in recognizing assembly tasks, and that it is possible to generate robot motion commands for repeating the same assembly task.
Tumour-infiltrating lymphocytes: A prognostic factor of PSA-free survival in patients with local prostate carcinoma treated by radical prostatectomy.

AIM The aim of the study was to evaluate the prognostic significance of tumour-infiltrating lymphocytes (TILs) in local prostate cancer (PC). MATERIALS AND METHODS TILs were counted and routine histological variables were assessed from radical prostatectomy specimens in 188 cases of PC. Immunohistochemical (IHC) characterisation of the lymphocytes was done by using CD4 and CD8 antibodies for detection of T lymphocytes and CD20 antibody for B lymphocytes in tissue microarray construction. The results of the lymphocyte analyses were compared to other prognostic factors and PSA recurrence-free survival (RFS). RESULTS Strong expression of TILs, CD4, CD8 and CD20 lymphocytes were seen in 28%, 33%, 35% and 15% of the cases, respectively. CD4 and CD8, as well as CD4 and CD20, lymphocytes were correlated to each other (p < 0.0001), but not to clinical or histopathological parameters. Weak expression of TILs was correlated with intracapsular carcinoma (p = 0.004), while perineural invasion (p = 0.017) and capsular invasion (p < 0.0001) were related to strong expression of TILs. Shortened PSA RFS was associated with strong expression of TILs (p = 0.005). In Cox regression analysis, independent predictors of shortened PSA RFS were strong expression of TILs (p = 0.012) and high Gleason score (p < 0.001). CONCLUSION TILs are an independent predictor of short PSA RFS in patients with local PC treated by radical prostatectomy.
Alexithymia, Interhemispheric Transfer, and Right Hemispheric Specialization: A Critical Review

Background: One neural model of alexithymia relates the condition to poor interhemispheric transfer, while another model associates it with a disturbance in right hemisphere activity. Methods: The available empirical evidence directly relating alexithymia to a deficit in interhemispheric transfer and/or in right hemisphere activity is critically reviewed. Results: The interhemispheric transfer studies have related alexithymia to a deficit in transfer, but the nature and directionality of the transfer deficit have yet to be determined. Many of the hemispheric specialization studies do not relate alexithymia to a right hemisphere dysfunction. Shortcomings of these studies are reviewed. Conclusions: The hypothesis that alexithymia is related to a deficit in the right-to-left transfer of emotional information and to a right hemisphere impairment in emotion processing remains to be tested directly and definitively. Suggestions for future research are made.
FURTHER OBSERVATIONS ON THE ZONE PHENOMENON IN THE BACTERICIDAL ACTION OF PENICILLIN

Effect of adiding high concentrations of penicillin to bacteria dying under the impact of low (optimal) concentrations. If zone-reacting bacteria are first exposed to (low) optimal concentrations of penicillin, at which they die rapidly, and if high concentrations of penicillin are subsequently added to the reacting mixture, the rate of death is promptly slowed toward that characteristic of the high concentrations. This is shown for a strain of Streptococcus faecalis in figure 1. The retarding effect of the high concentrations was evidenced even if the organisms had previously been exposed to the optimal concentration for 2 hours, when more than 99 per cent had already been rendered nonviable. A qualitatively similar but quantitatively less pronounced effect was observed with a group B streptococcus. The lasting effects of brief exposure to high concentrations of penicillin. The paradoxical retardation of the bactericidal effect caused by high concentrations of penicillin is due to a positive interaction between the drug and the cell, and the effects of that interaction persist after the removal of the drug. If zonesensitive bacteria are first placed in a high concentration of penicillin, at which they die at a relatively slow rate, and if after several hours' incubation the mixture is diluted so that the concentration of penicillin is reduced to the maximally effective level, the rate of death is not thereby accelerated to that characteristic of the lower concentration. Instead, the organisms continue to die at the slow rate established by the high concentration. A typical experiment with Streptococcus faecalis is shown in figure 2, and a similar experiment with a group B streptococcus is shown in figure 3. The death-delaying action of the high concentration of penicillin clearly persists after the removal of the excess drug. Exposure to high concentrations for as short a time as 15 minutes, long before a significant number of organisms had been killed, sufficed to exert this protective action. DISCUSSION2 It is difficult to explain the foregoing observations on any basis other than that penicillin has at least two qualitatively distinct effects on certain strains of bac-
Musculoskeletal Rehabilitation: Current Understandings and Future Directions

Dillingham TR: Musculoskeletal rehabilitation: current understandings and future directions. Am J Phys Med Rehabil 2007;86(Suppl):S19–S28. This work examines the current state of knowledge regarding the efficacy of rehabilitation for patients with major lower-extremity joint replacements, hip fractures, and amputations. Of particular focus is the use of inpatient rehabilitation strategies for functional restoration. These areas of rehabilitation involve common conditions in the elderly population. Cost-containment pressures have highlighted the focus on the efficacy of inpatient rehabilitation for persons with joint replacements in particular. Medicare’s “75% rule” specifically limits persons with elective joint replacements from entering rehabilitation units after their surgeries. This article highlights research relevant to these issues and was written to examine the state of knowledge about these topics with the goal of highlighting areas that need more research attention.