Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum erythropoietin and erythropoiesis in high- and low-fetal hemoglobin beta-thalassemia intermedia patients.

Clinical data suggest that in beta-thalassemia-intermedia patients, higher levels of circulating fetal hemoglobin (HbF) are associated with greater disease severity at comparable degrees of anemia. We assessed the influence of the amount of circulating HbF on serum erythropoietin (s-Epo) levels and on serum transferrin receptor, a measure of erythropoiesis, in 30 beta-thalassemia-intermedia patients. Twenty-four showed more than 40% HbF (21 of whom with beta (0)-thalassemia) and 6 presented lower HbF levels (beta(+)-thalassemia). The two groups of patients did not differ in age (15.3 v 19 years, respectively) or degree of anemia (Hb = 8.8 g/dL in both groups). Log (s-Epo) was correlated inversely with Hb (r = -0.47; P < .01), and directly with HbF (r = .55; P < .001). Multivariate regression analysis showed that Hb and HbF were independently correlated with s-Epo levels. High-HbF patients had greater s-Epo values at the same Hb level than low-HbF patients. Considering that iron-deficiency anemia control patients represented the predicted physiologic response of s-Epo to anemia, the observed/predicted s-Epo ratio in low-HbF thalassemic patients was no different from controls, but was increased in the high-HbF group. High-HbF patients also showed an expansion of erythropoiesis as much as four to nine times the normal value at the same Hb level as low-HbF patients. We conclude that HbF exerts an independent regulatory effect on erythropoietin production and erythropoiesis that is detectable only when HbF levels exceed 40%.
Hydroxyethyl starch or saline in intensive care.

To the Editor: Myburgh et al. (Nov. 15 issue)1 report the results of the Crystalloid versus Hydroxyethyl Starch Trial (CHEST), which showed no significant difference in mortality between patients resuscitated with either 6% hydroxyethyl starch (HES) with a molecular weight of 130 kD and a molar substitution ratio of 0.4 (130/0.4) or saline in the intensive care unit. The intention-totreat analysis was performed in a relatively smaller, randomized population than that in the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) study2 or, for the safety analysis, than that in our recently published Crystalloids Morbidity Associated with Severe Sepsis (CRYSTMAS) study.3 Since errors in the administration of study fluid were reported in 9.5% of each study group (see the Supplementary Appendix of the article, available at NEJM.org), it is important to perform a per-protocol analysis. With regard to renal function, analysis with the use of the five-category scoring system for evaluating risk, injury, failure, loss, and end-stage kidney injury (RIFLE) was apparently performed according to subclasses for being at risk for kidney dysfunction (RIFLE-R), for injury to the kidney (RIFLE-I), and for failure of kidney function (RIFLE-F) and was not performed globally, as in the CRYSTMAS study. Finally, the results of analysis of the incidence of renal-replacement therapy are very difficult to interpret, since the P value is 0.04 but the 95% confidence interval for the relative risk includes 1. After adjustment for covariates, the difference is no longer significant (P = 0.05). These borderline results should have been taken into account by the authors in their conclusions with regard to renal-replacement therapy. Bertrand Guidet, M.D.
The Market for Liars: Reputation and Auditor Honesty

In the model there are two types of financial auditors with identical technology, one of which is endowed with a prior reputation for honesty. We characterize conditions under which there exists a "two-tier equilibrium" in which "reputable" auditors refuse bribes offered by clients for fear of losing reputation, while "disreputable" auditors accept bribes because even persistent refusal does not create a good reputation. The main findings are: (a) honest auditors charge higher fees, and have economic profits accruing to reputation; (b) as the fraction of auditors who are honest increases, the premium charged by reputable auditors eventually decreases, which diminishes the incentive to refuse bribes; (c) if the fraction of honest auditors exceeds an upper bound, there does not exist a two-tier equilibrium; (d) thus the reputation mechanism may be undermined by entry into the honest segment of the industry, if it is possible; (e) increasing auditor independence increases the upper bound.
Adolescent versus adult responses to vertical spinal loading

This study compared the vertical spinal creep response between adolescent and adult males. Thirty healthy male subjects, 15 adolescents (aged 12 to 16 years) and 15 adults (aged 30 to 57 years) were measured. Spinal creep was measured continuously over 25 min under loaded and unloaded conditions using a seated stadiometer that controlled spinal posture. Both adolescent and adult subjects showed significant increase in vertical spinal creep with time but the magnitude of vertical spinal creep was significantly greater in adolescent than in the adult subjects.
Ensemble evaluation and projection of climate extremes in China using RMIP models

Under the framework of the Regional Climate Model Intercomparison Project (RMIP III), simulation results from six regional climate models (RCMs) and two global climate models (GCMs) were used to generate climate extreme indices for the present and future over China using two ensemble methods. All the models reasonably captured the observed climate extremes, and performance‐based ensemble averaging (PEA) outperformed the individual model and equal‐weighted averaging (MME) for the control climate. However, noticeable cold deficiencies in temperature extremes were found over areas with complex topography, and too frequent heavy precipitation at smaller intensities was simulated using the multiple model ensembles. Under the A1B scenario for 2041–2060, widespread increases in the 90th percentiles of the maximum temperatures (Tmax90p) and the 10th percentile of the minimum temperatures (Tmin10p) were projected, with larger increases in winter than in summer. Greater intensities in precipitation extremes were projected over China, with the exception of Inner Mongolia. Large uncertainties exist in the projected mean diurnal temperature range (Trange), number of days with precipitation exceeding 10 mm (R10) and the maximum number of consecutive dry days (CDD) because of disagreements in both the magnitudes and signs of the climate model projections, and even the two ensemble methods presented opposite signs over some regions.
Interactions between drifting snow and surface dynamics

In the cryosphere, the snow cover is the fastest changing component. Amongst other characteristics, the snow cover acts as a resource of water or has the ability to reflect the suns radiation and therefore significantly influence the climate on a global scale. During the winter period in the northern hemisphere, up to 23% of the earth’s surface is covered with snow. In alpine regions starting at a certain elevation or at high latitudes, snow is the predominant state of the surface during winter time. Changes in the distribution of this snow cover are driven by different processes such as precipitation or melting. One main driver for the changes of this snow cover is aeolian transport, the transport of snow by the wind which is often referred to as drifting and blowing snow. In polar regions with predominant snow surfaces, little precipitation and subfreezing temperatures the redistribution of snow has a major role for the hydrological mass balance. Besides the redistribution of mass as a hydrological resource, in alpine regions, the redistribution of snow also has a major effect on the danger of avalanches. Understanding how the snow surface responds to the forces of the wind is the key to understand the subsequent redistribution of the snow. Aeolian transport of snow has been previously described in literature, mainly focusing on the transport of the particles in the boundary layer, also with reasonable temporal resolution. Little attention has been given to the quantification of changes at the snow surface. This work takes a new approach to look at the changes of the snow surface in combination with the horizontal mass-flux during events of drifting snow. It aims to quantify these changes on a relatively high spatial and temporal resolution by means of a Kinect sensor. This dissertation is divided in four sections. Chapter 1 introduces the concepts and theoretical background of drifting and blowing snow as well as outlining the thesis. Each subsequent chapter presents the main results as they have been or will be published in journal articles (Chapter 2-4). In Chapter 2 we compare two of the most common methods of quantifying mass flux, particle numbers and particle-size distribution for drifting snow events, (i) the snow-particle counter (SPC), a laser-diode-based particle detector, and (ii) particle tracking velocimetry based on digital shadowgraphic imaging. The two methods were correlated for mass flux and particle number flux. A calibration study with artificially scattered sand particles and glass beads provides suitable settings for the shadowgraphical imaging as well as obtaining a first correlation of the two methods in a controlled environment. In addition, using snow collected in trays during snowfall, several experiments were performed to observe drifting snow events in a cold wind tunnel. The results demonstrate a high correlation between the
Finding Four-Node Subgraphs in Triangle Time

We present new algorithms for finding induced four-node subgraphs in a given graph, which run in time roughly that of detecting a clique on three nodes (i.e., a triangle). • The best known algorithms for triangle finding in an n-node graph take O(nω) time, where ω < 2.373 is the matrix multiplication exponent. We give a general randomized technique for finding any induced four-node subgraph, except for the clique or independent set on 4 nodes, in O(nω) time with high probability. The algorithm can be derandomized in some cases: we show how to detect a diamond (or its complement) in deterministic O(nω) time. Our approach substantially improves on prior work. For instance, the previous best algorithm for C4 detection ran in O(n3.3) time, and for diamond detection in O(n3) time. • For sparse graphs with m edges, the best known triangle finding algorithm runs in O(m2ω/(ω+1)) ≤ O(m1.41) time. We give a randomized O(m2ω/(ω+1)) time algorithm (analogous to the best known for triangle finding) for finding any induced four-node subgraph other than C4, K4 and their complements. In the case of diamond detection, we also design a deterministic O(m2ω/(ω+1)) time algorithm. For C4 or its complement, we give randomized O(m(4ω−1)/(2ω+1)) ≤ O(m1.48) time finding algorithms. These algorithms substantially improve on prior work. For instance, the best algorithm for diamond detection ran in O(m1.5) time.
Preliminary lexicostatistics as a basis for language classification: a new approach

The article discusses the basic methodology that underlies the construction of a global lexicostatistical database for all of the world’s languages, currently one of the main tasks of the Evolution of Human Languages project at the Santa Fe Institute. The author presents several important modifications of the traditional lexicostatistical procedure, such as: replacing the traditional 100­item wordlist with a more compact list of 50 “ultra-stable” items; use of lowlevel protolanguage reconstructions as primary construction nodes; a combination of the comparative-historical method and principles of phonetic similarity as the basis for the cognate scoring procedure; and, most importantly, a heavy emphasis on semantic precision and severe restrictions on the use of synonyms.
Full-Duplex Millimeter-Wave Communication

The potential of doubling the spectrum efficiency of FD transmission motivates us to investigate FD-mmWave communication. To realize FD transmission in the mmWave band, we first introduce possible antenna configurations for FD-mmWave transmission. It is shown that, different from the cases in microwave band FD communications, the configuration with separate Tx/Rx antenna arrays appears more flexible in SI suppression while it may increase some cost and area versus that with the same array. We then model the mmWave SI channel with separate Tx/Rx arrays, where a near-field propagation model is adopted for the LOS path, and it is found that the established LOS-SI channel with separate Tx/Rx arrays also shows spatial sparsity. Based on the SI channel, we further explore approaches to mitigate SI by signal processing, and we focus on a new cancellation approach in FD-mmWave communication, that is, beamforming cancellation. Centered on the CA constraint of the beamforming vectors, we propose several candidate solutions. Lastly, we consider an FD-mmWave multi-user scenario, and show that even if there are no FD users in an FD-mmWave cellular system, the FD benefit can still be exploited in the FD base station. Candidate solutions are also discussed to mitigate both SI and MUI simultaneously.
In vivo biologic effects of PIXY321, a synthetic hybrid protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 in cancer patients with normal hematopoiesis: a phase I study.

PIXY321 is a novel fusion protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 that exhibits biologic effects of both its parent cytokines in vitro and in preclinical studies. To evaluate the clinical safety and hematopoietic effects of this hybrid cytokine, PIXY321 was administered by subcutaneous injection twice daily at doses of 25 to 1,000 micrograms/m2/day over 14 days to 24 patients with sarcoma before chemotherapy as part of a phase I trial. The treatment was associated with significant increases in white blood cell, neutrophil, platelet, and reticulocyte counts (all P < .001). The increase in neutrophil count was dose-related and was seen during treatment with the cytokine, whereas the increase in platelet count was gradual and peaked after the cessation of the cytokine treatment and was not clearly dose related. PIXY321 treatment also increased bone marrow (BM) cellularity and the percentage of BM cells in S phase (P < .001). In addition, there was a significant increase in the number of CD34+ cells and committed and multipotential progenitors in the peripheral blood. The ex vivo expansion capacity of peripheral blood and BM progenitor cells was preserved after the in vivo treatment with PIXY321. The treatment was well tolerated, with the most common side-effect being injection site reactions. The results of this study show the biologic and clinical activity of a genetically engineered fusion molecule of two hematopoietic cytokines in humans with normal hematopoietic function.
The Saline Load Test of the Knee Redefined: A Test to Detect Traumatic Arthrotomies and Rule Out Periarticular Wounds Not Requiring Surgical Intervention

Objective: To describe the use of the saline load test (SLT) using a new definition that more adequately characterizes its use in the emergency department (ED) setting. Design: Retrospective review. Setting: Level I trauma center. Patients/Participants: Fifty consecutive patients who underwent an SLT of the knee in the ED and had a minimum of 14 days follow-up. Intervention: Saline Load Test. Main Outcome Measurements: Positive traumatic arthrotomy of the knee (+TAK) defined as operating room (OR) confirmation of an arthrotomy (assumed to develop a septic knee) or −SLT with follow-up revealing a septic knee. Periarticular wound equivalent to no traumatic arthrotomy of the knee [pw = (−TAK)] defined as OR evaluation revealing no arthrotomy (assumed not to develop a septic knee) or −SLT whose follow-up revealed no septic knee. Development of a septic knee was considered the gold standard for determining true positives/negatives and false positives/negatives. Results: The mean wound size was 3.9 ± 4.3 cm and the mean saline load volume was 74.9 ± 28.2 cm. There were 19 +SLTs of which there were 16 +TAK and 3 pw = (−TAK). The 3 pw = (−TAK) in the +SLT group were evaluated in the OR where inspection of the joint capsule revealed the absence of a traumatic arthrotomy. There were 31 −SLTs of which there were 1 +TAK and 30 pw = (−TAK). The SLT has a sensitivity of 94% and a specificity of 91% for detecting +TAKs and ruling out periarticular wounds not requiring surgical intervention [pw = (−TAK)]. The false-positive rate of the SLT to detect +TAK is 9%. Conclusions: Using +TAK and pw = (−TAK) as the newly defined measures of the SLT, we report the sensitivity (94%) and specificity (91%) of the SLT in the ED setting while still maintaining the clinical relevancy of the test. Based on a small sample size, knees with small periarticular wounds and a −SLT and no other radiographic or clinical evidence of an arthrotomy appear to have an infection rate of 0% with nonoperative management. Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence

Significance Childhood maltreatment is a major risk factor for internalizing disorders including depression and anxiety, which cause significant disability. Altered connectivity of the brain’s fear circuitry represents an important candidate mechanism linking maltreatment and these disorders, but this relationship has not been directly explored. Using resting-state functional brain connectivity in adolescents, we show that maltreatment predicts lower prefrontal–hippocampal connectivity in females and males but lower prefrontal–amygdala connectivity only in females. Altered connectivity, in turn, mediated the development of internalizing symptoms. These results highlight the importance of fronto–hippocampal connectivity for both sexes in internalizing symptoms following maltreatment. The additional impact on fronto–amygdala connectivity in females may help explain their higher risk for anxiety and depression. Maltreatment during childhood is a major risk factor for anxiety and depression, which are major public health problems. However, the underlying brain mechanism linking maltreatment and internalizing disorders remains poorly understood. Maltreatment may alter the activation of fear circuitry, but little is known about its impact on the connectivity of this circuitry in adolescence and whether such brain changes actually lead to internalizing symptoms. We examined the associations between experiences of maltreatment during childhood, resting-state functional brain connectivity (rs-FC) of the amygdala and hippocampus, and internalizing symptoms in 64 adolescents participating in a longitudinal community study. Childhood experiences of maltreatment were associated with lower hippocampus–subgenual cingulate rs-FC in both adolescent females and males and lower amygdala–subgenual cingulate rs-FC in females only. Furthermore, rs-FC mediated the association of maltreatment during childhood with adolescent internalizing symptoms. Thus, maltreatment in childhood, even at the lower severity levels found in a community sample, may alter the regulatory capacity of the brain’s fear circuit, leading to increased internalizing symptoms by late adolescence. These findings highlight the importance of fronto–hippocampal connectivity for both sexes in internalizing symptoms following maltreatment in childhood. Furthermore, the impact of maltreatment during childhood on both fronto–amygdala and –hippocampal connectivity in females may help explain their higher risk for internalizing disorders such as anxiety and depression.
Peripartum hysterectomy for primary postpartum haemorrhage: Incidence and maternal morbidity

Summary This was a retrospective analysis of postpartum emergency hysterectomy performed between 1988 – 2003, to study incidence indicators, risk factors and complications. We included any women who required emergency hysterectomy to control major postpartum haemorrhage (PPH) after delivery, following a pregnancy of at least 24 weeks' gestation, regardless of the mode of delivery. We excluded cases that required a hysterectomy for gynaecological reasons. There were 18 cases of emergency hysterectomy (14 caesarean hysterectomy and four postpartum hysterectomy, after vaginal delivery), giving a rate of 0.36/1,000 deliveries. Overall, the most common indication for hysterectomy was placenta accreta (28%) and uterine atony (28%). Although there was no maternal death, intra- and postoperative complications were prevalent including cardiac arrest (1), disseminated intravascular coagulopathy (4), pulmonary oedema (1), septicaemia (1), and bladder injury (1). Placenta accreta is becoming a leading cause of emergency postpartum hysterectomy. Although hysterectomy is a life saving operation, it is associated with high maternal morbidity.
Biphenyl 2,3′,4,5′,6‐pentakisphosphate, a novel inositol polyphosphate surrogate, modulates Ca2+ responses in rat hepatocytes

Benzene polyphosphates containing phosphate groups on one ring are Ins(1,4,5)P3 5‐phosphatase inhibitors when evaluated against type‐I Ins(1,4,5)P3 5‐phosphatase. A novel biphenyl derivative, biphenyl 2,3′,4,5′,6‐pentakisphosphate, with five phosphate groups on two rings was synthesized: It inhibited the activity of two inositol 5‐phosphatases: type I and SHIP2 with Ins(1,3,4,5)P4 as substrate. The inhibition was competitive with respect to the substrate. IC50 value measured in rat hepatocytes, which contains the native Ins(1,4,5)P3 5‐phosphatase, was in the micromolar range at 1.0 μM Ins(1,4,5)P3 as substrate. Biphenyl 2,3′,4,5′,6‐pentakisphosphate did not affect the activity of Ins(1,4,5)P3 3‐kinase A in the 5‐100 μM range. Surprisingly, experimental evidence supports an effect of biphenyl 2,3′,4,5′,6‐pentakisphosphate at the level of the Ins(1,4,5)P3 receptor. Finally, when injected into rat hepatocytes, the analog affected the frequency of Ca2+ oscillations in a positive or negative way depending on its concentration. At very high concentrations of the analog, Ca2+ oscillations were even suppressed. These data were interpreted as a dual effect of the biphenyl 2,3′,4,5′,6‐pentakisphosphate on cytosolic [Ca2+] increases: an activation effect through an increase in Ins(1,4,5)P3 level via Ins(1,4,5)P3 5‐phosphatase inhibition and an inhibitory effect, which was exerted directly on the Ins(1,4,5)P3 receptor. Thus, our data show for the first time that the frequency of Ca2+ oscillations in response to a Ca2+‐mobilizing agonist can be controlled by inhibitors of type‐I Ins(1,4,5)P3 5‐phosphatase. —Vandeput, F. , Combettes, L. , Mills, S. J., Backers, K. , Wohlkönig, A. , Parys, J. B. , De Smedt, H. , Missiaen, L. , Dupont, G. , Potter, B. V. L. , Erneux, C. Biphenyl 2,3′,4,5′,6‐pentakisphosphate, a novel inositol polyphosphate surrogate, modulates Ca2+ responses in rat hepatocytes. FASEB J. 21, 1481–1491 (2007)
Geometrical Singularities in the Neuromanifold of Multilayer Perceptrons

Singularities are ubiquitous in the parameter space of hierarchical models such as multilayer perceptrons. At singularities, the Fisher information matrix degenerates, and the Cramer-Rao paradigm does no more hold, implying that the classical model selection theory such as AIC and MDL cannot be applied. It is important to study the relation between the generalization error and the training error at singularities. The present paper demonstrates a method of analyzing these errors both for the maximum likelihood estimator and the Bayesian predictive distribution in terms of Gaussian random fields, by using simple models.