Miracle-dz/UniFAR-FTUs huggingface dataset:
A Model for a Multicentre Approach to the Derivation of Reference Intervals for Thyroid Hormones and Testosterone for Laboratories Using Identical Analysers

Abstract Ideally, every laboratory should derive their own reference intervals for all analytes, but this is difficult in practice. A survey, by questionnaire, of UK laboratories using the Chiron Diagnostics ACS:180 (Chiron Diagnostics Limited, Halstead, Essex, UK), for thyroid function tests, showed that 10% of laboratories derived their own reference intervals, 60% quoted values “adapted” from intervals for previous methods, whilst the remaining 40% quoted (often incorrectly) reference intervals supplied by the manufacturer. In addition only 13% of respondent laboratories derived their own reference intervals for testosterone. As a result of this survey, a study was devised to enable the users of the Chiron Diagnostics ACS:180 immunoassay system to develop and use within-method, between-laboratory reference intervals for thyroid hormones and testosterone. Laboratory collaboration provided the recommended minimum number of data points by establishing a reference sample group. This sample group was used for the calculation of appropriate reference intervals for each hormone according to the guidelines published by the IFCC. We propose this approach as a model for laboratories using identical instrumentation to produce, through collaboration, within-method, between laboratory reference intervals.
Non-Determinism and the Dynamics of Knowledge

In this paper we attempt to shed light on the concept of an agent’s knowledge after a non-deterministic action is executed. We start by making a comparison between notions of non-deterministic choice, and between notions of sequential composition, of settings with dynamic and/or epistemic character; namely Propositional Dynamic Logic (PDL), Dynamic Epistemic Logic (DEL), and the more recent logic of Semi-Public Environments (SPE). These logics represent two different approaches for defining the aforementioned actions, and in order to provide unified frameworks that encompass both, we define the logics DELVO (DEL+Vision+Ontic change) and PDLVE (PDL+Vision+Epistemic operators). DELVO is given a sound and complete axiomatisation.
Nearly Linear-Time Approximation Schemes for Mixed Packing/Covering and Facility-Location Linear Programs

We describe nearly linear-time approximation algorithms for explicitly given mixed packing/covering and facility-location linear programs. The algorithms compute $(1+\epsilon)$-approximate solutions in time $O(N \log(N)/\epsilon^2)$, where $N$ is the number of non-zeros in the constraint matrix. We also describe parallel variants taking time $O(\text{polylog}/\epsilon^4)$ and requiring only near-linear total work, $O(N \text{polylog} /\epsilon^2)$. These are the first approximation schemes for these problems that have near-linear-time sequential implementations or near-linear-work polylog-time parallel implementations.
Doppler ultrasound assessment of cerebral blood flow in the human fetus

Summary. A mechanical sector and linear array real‐time scanner combined with a pulsed Doppler system was used for recording the flow velocity waveform in the internal carotid artery, the lower thoracic part of the descending aorta and umbilical artery in the human fetus. A total of 42 fetuses in normal pregnancy and nine growth‐retarded fetuses between 26 and 41 weeks gestation was studied. In normal pregnancy the mean pulsatility index (PI) in the internal carotid artery varied between 1·5 and 1·6, in the descending aorta between 1·7 and 1·8 and in the umbilical artery between 0·7 and 1·3. In the growth‐retarded fetuses the PI was reduced in the internal carotid artery and raised in the descending aorta and umbilical artery, suggesting an increased peripheral vascular resistance in the fetal body and placenta and a compensatory reduction in peripheral vascular resistance in the fetal cerebrum, i.e. a brain‐sparing effect in the presence of fetal hypoxia.
The immunophenotypes of blast cells in B‐cell precursor acute lymphoblastic leukemia: How different are they from their normal counterparts?

Currently, there are three major maturational stages of CD19 antigen expressing B‐cell precursors (hematogones). In B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), the malignant counterpart of hematogones, the leukemic blasts share common phenotypic features. The aim of the study was to enumerate the actual differences between the leukemic blasts in the CD10+ and CD10− subgroups of BCP‐ALL and hematogones by assessing the expression of the antigens: TdT, CD34, CD45, CD10, CD38, CD20 and CD22.
Persistent HIV infection in newborns: how soon is soon enough?

Over the last few years, attention has been drawn to efforts that seek to develop a cure for HIV infection. Investigators and scientists seek to completely eradicate HIV infection (called by some a sterilizing cure), or allow patients to interrupt antiretroviral therapy (ART) without the risk of viral rebound, viral transmission, or progressive disease (known as a functional cure). This wave of interest has been spurred by anecdotes of actual cure in real patients, first in Timothy Brown [1,2], and then more recently in two additional marrow transplant patients in Boston [3], and a newborn treated hours after birth – the ‘Mississippi baby. ’ [4]. However, the relatively rapid return of viremia in the Boston patients is a sobering reminder of the challenges ahead.
Primary Peritoneal Carcinoma: A Report of Twelve Cases and a Review of the Literature

Primary peritoneal carcinoma (PPC) is rare tumor histologically identical to epithelial ovarian carcinoma (EOC); it is differentiated from EOC based on the extent of gross ovarian involvement and microscopic invasion of the cortex. We report 12 cases of PPC which were diagnosed in our Department during a 9-year period. Total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy were performed in 9 patients, while 3 underwent only explorative laparotomy with bilateral salpingo-oophorectomy. All patients were treated with postoperative platinum-based chemotherapy. After a median follow-up of 42 months, only 5 patients are alive without disease. PPC is a rare tumor currently managed in the same way as ovarian cancer. Primary debulking surgery and chemotherapy represent the cornerstones of treatment. Considering the limited number of patients with PPC, no definitive conclusion can be drawn concerning the prognostic factors for survival.
Halothane Increases Epinephrine Threshold for the Development of Slow Responses in Isolated Canine Trabeculae

We studied halothane/epinephrine interaction in isolated canine trabeculae using the doses of epinephrine necessary to produce slow responses (epinephrine threshold for the development of slow responses, ETSR) as an indicator. The preparations were depolarized in Tyrode's solution containing 26 mmol/L of KC1, then epinephrine concentrations in the solution were increased in a stepwise manner. Halothane (1%) had no significant effect, whereas 2% and 4% halothane significantly increased the ETSR. α1 Blockade with either 4, 8, or 16 ng/mL of prazosin or 20, 40, or 80 ng/mL of droperido! did not alter the ETSR, whereas β1-adrenergic blockade with 8, 17, or 34 ng/mL of metoprolol significantly increased the ETSR. The same trend was observed when either 8 ng/mL of prazosin or 17 ng/mL of metoprolol was given in combination with 2% halothane. Verapamil (5, 10, or 20 ng/mL) increased the ETSR in a dose-dependent manner. These results indicate that halothane decreases rather than increases the sensitivity of slow calcium channels to epinephrine and that any increase above the baseline ETSR after halothane administration cannot be ascribed to halothane/adrenoceptor interaction but rather to calcium entry-blocking effects of halothane. As slow responses are induced by the activation of slow calcium channels, our findings are consistent with known data that halothane can interfere with slow calcium channel conductance.
Familial Language Impairment:More English Evidence

Subjects between the ages of 9 and 22 with a history of familial language impairment were tested on a wide range of linguistic tasks. The data show that they are not different from the non-impaired members of their family or from external controls in their ability to hear and understand the morphological marker for plural or to understand a narrative, but they are significantly different in recognizing or correcting grammatical errors, in producing tense or number marking, and in understanding sentences with non-canonical word order. This pattern of deficits is similar to that which occurs cross-linguistically and in on-line processing tasks. These data support the hypothesis that these subjects do not build normal representations in their grammar nor construct productive grammatical rules. However, they are able to use other means such as memory and explicit rules to simulate grammar.
Immunogenicity of a 48-Kilodalton Recombinant T-Cell-Reactive Protein of Coccidioides immitis

ABSTRACT The outcome of coccidioidomycosis depends to a large extent on the effectiveness of the T-cell-mediated immune (CMI) response to the fungal pathogen. For this reason, identification of Coccidioides immitis antigens which stimulate T cells is important for understanding the nature of host defense against the organism and essential for the development of an effective vaccine. Here we describe the immunogenicity of a 48-kDa T-cell-reactive protein (TCRP). The antigen is expressed by parasitic cells and localized in the cytoplasm. It stimulates the proliferative response and production of gamma interferon by T cells of mice immunized with C. immitisspherules. Specific antibody reactive with the recombinant TCRP (rTCRP) was detected in sera of patients with confirmed coccidioidal infection, and the highest titers of antibody to the recombinant protein correlated with elevated titers to the serodiagnostic complement fixation antigen of C. immitis. These results suggest that the TCRP is presented to the host during the course of infection. Immunization of BALB/c and C3H/HeN mice with the rTCRP affords a modest but significant level of protection against an intraperitoneal challenge with C. immitis. It is suggested that the rTCRP may be able to contribute to a multicomponent vaccine designed to stimulate CMI response against the parasitic cycle of C. immitis.
World-line quantum Monte Carlo algorithm for a one-dimensional Bose model.

In this paper we provide a detailed description of the ground-state phase diagram of interacting, disordered bosons on a lattice. We describe a quantum Monte Carlo algorithm that incorporates in an efficient manner the required bosonic wave-function symmetry. We consider the ordered case, where we evaluate the compressibility gap and show the lowest three Mott insulating lobes. We obtain the critical ratio of interaction strength to hopping at which the onset of superfluidity occurs for the first lobe, and the critical exponents {nu} and {ital z}. For the disordered model we show the effect of randomness on the phase diagram and the superfluid correlations. We also measure the response of the superfluid density, {rho}{sub {ital s}}, to external perturbations. This provides an unambiguous characterization of the recently observed Bose and Anderson glass phases.
Distal Anterior Interosseous Nerve Transfer to the Deep Motor Branch of the Ulnar Nerve for Reconstruction of High Ulnar Nerve Injuries

Proximal ulnar nerve injuries can result in loss of intrinsic muscle function of the hand, and distal nerve transfers provide nerve coaptation close to the target muscle. This retrospective chart review evaluated patient outcome following a distal nerve transfer of the anterior interosseous nerve (AIN) to the deep motor branch of the ulnar nerve. There were eight patient charts reviewed, three women, and five men. The mean patient age was 38 years (standard deviation: 22 years). The mean time from injury to surgery was 3 months (standard deviation: 3 months), and mean postoperative follow-up time was 18 months (standard deviation: 11 months). All patients had reinnervation of the ulnar nerve intrinsic hand muscles with improved postoperative lateral pinch and grip strength. One patient had a secondary tendon transfer. No functional deficit in performing tasks in pronation was reported. The distal nerve transfer of the AIN to the deep motor branch of the ulnar nerve provides good reinnervation of the ulnar-nerve-innervated intrinsic muscles of the hand.
Neural Correlates of Letter-String Length and Lexicality during Reading in a Regular Orthography

Behavioral studies have shown that short letter strings are read faster than long letter-strings and words are read faster than nonwords. Here, we describe the dynamics of letter-string length and lexicality effects at the cortical level, using magnetoencephalography, during a reading task in Finnish with long (eight-letter) and short (four-letter) word/nonword stimuli. Length effects were observed in two spatially and temporally distinct cortical activations: (1) in the occipital cortex at about 100 msec by the strength of activation, regardless of the lexical status of the stimuli, and (2) in the left superior temporal cortex between 200 and 600 msec by the duration of activation, with words showing a smaller effect than nonwords. A significant lexicality effect was also evident in this later activation, with stronger activation and longer duration for nonwords than words. There seem to be no distinct cortical areas for reading words and nonwords. The early length effect is likely to be due to the low-level visual analysis common to all stimulus letter-strings. The later lexicality and length effects apparently reflect converging lexico-semantic and phonological influences, and are discussed in terms of dual-route and single-route connectionist models of reading.
Temporal and quantitative profiles of growth factors and metalloproteinases in acute wound fluid after mastectomy

Seventy‐three samples of acute wound fluid were collected from 47 patients during the first 3 postoperative days (POD) following mastectomy for cancer (n=47 on POD‐1, n=19 on POD‐2, and n=7 POD‐3). Samples were analyzed by enzyme‐linked immunosorbent assay for growth factor levels (epidermal [EGF], platelet‐derived [PDGF], basic fibroblast [bFGF], transforming growth factor‐β1 [TGF‐β1], vascular endothelial [VEGF]), interleukin‐6 (IL‐6), matrix metalloproteinases (MMPs‐2, ‐3, ‐9), and the tissue inhibitor of metalloproteinase 1 (TIMP‐1). The levels of EGF, bFGF, PDGF, and interleukin‐6 peaked on POD‐1, with a significant decrease by POD‐3, while total and active MMP‐2, MMP‐3, and tissue inhibitor of metalloproteinase 1 showed a progressive and significant increase from days 1 to 3. The wounds that later developed an infection (11%) were found to have a significantly lower PDGF and EGF on day 1 (PDGF, median 169 pg/mL [range, 86–2,595]) than the noninfected wounds (2,098 [17–66,506] p<0.05, Mann–Whitney U‐test). Sixty‐two percent patients developed a seroma and the levels of bFGF were significantly less in these patients (441 pg/mL [45–4,108]) than in those patients where there was no seroma (807 [245–3,133] p<0.05). The levels of certain growth factors in acute wound fluid may be important markers for wound outcomes.
Estrogen-independent proliferation is present in estrogen-receptor HER2-positive primary breast cancer after neoadjuvant letrozole.

PURPOSE To investigate the impact of human epidermal growth factor receptor (HER) 1 and HER2 gene amplification on endocrine therapy responsiveness, a fluorescence in situ hybridization (FISH) study was conducted on tumor samples from 305 postmenopausal patients with stage II and III estrogen receptor (ER) -positive (ER > or = 10%) breast cancers treated on two independent neoadjuvant endocrine therapy trials. PATIENTS AND METHODS FISH analysis focused on HER1 and/or HER2 immunohistochemistry (IHC) -positive patients and a random selection of HER1/2 IHC-negative patients. HER2 FISH status was correlated with response and changes in the proliferation marker Ki67. RESULTS HER1 was rarely amplified (< 1%), and HER2 amplification was observed in 9.2% of patients. Letrozole response by clinical measurement (71% HER2 FISH positive v 71% HER2 FISH negative), mammogram (44% HER2 FISH positive v 47% HER2 FISH negative), or ultrasound (47% HER2 FISH positive v 54% HER2 FISH negative) was not impaired by HER2 FISH-positive status. In contrast, HER2 FISH-positive tumors showed higher histologic grade (P = .009), higher pretreatment Ki67 (P = .005), and less Ki67 suppression after letrozole when compared with HER2 FISH-negative tumors (P = .0001). Similar observations regarding Ki67 were made in a smaller cohort of tamoxifen-treated tumors. CONCLUSION Neoadjuvant letrozole is clinically effective in ER-positive HER2 FISH-positive tumors, indicating sensitivity to short-term estrogen deprivation. However, continued proliferation despite ongoing letrozole or tamoxifen treatment in the majority of ER-positive HER2 FISH-positive samples (88%) could imply therapeutic resistance that may manifest later in the clinical course of the disease. Discordance between clinical and biomarker findings in this study serves to emphasize the need for surrogate end point validation in neoadjuvant endocrine trials through correlation with information on long-term outcomes.
TNFRSF25 Agonistic Antibody and Galectin-9 Combination Therapy Controls Herpes Simplex Virus-Induced Immunoinflammatory Lesions

ABSTRACT Ocular infection with herpes simplex virus 1 (HSV-1) results in a chronic immunoinflamammtory reaction in the cornea, which is primarily orchestrated by CD4+ T cells. Hence, targeting proinflammatory CD4+ T cells or increasing the representation of cells that regulate their function is a relevant therapeutic strategy. In this report, we demonstrate that effective therapeutic control can be achieved using a combination of approaches under circumstances where monotherapy is ineffective. We use a convenient and highly effective monoclonal antibody (MAb) approach with MAbT25 to expand cells that express the tumor necrosis factor receptor superfamily member 25 (TNFRSF25). In naïve animals, these are predominantly cells that are Foxp3-positive regulatory T cells. MAbT25 treatment before or at the time of initial HSV infection was an effective means of reducing the severity of subsequent stromal keratitis lesions. However, MAbT25 treatment was not effective if given 6 days after infection since it expanded proinflammatory effector T cells, which also express TNFRSF25. Therefore, the MAbT25 procedure was combined with galectin-9 (Gal-9), an approach that compromises the activity of T cells involved in tissue damage. The combination therapy provided highly effective lesion control over that achieved by treatment with one of them. The beneficial outcome of the combination therapy was attributed to the expansion of the regulatory T cell population that additionally expressed activation markers such as CD103 needed to access inflammatory sites. Additionally, there was a marked reduction of CD4+ gamma interferon-producing effector T cells responsible for orchestrating the tissue damage. The approach that we describe has potential application to control a wide range of inflammatory diseases, in addition to stromal keratitis, an important cause of human blindness.
Three-dimensional ground displacements from static pipe bursting in stiff clay

Three-dimensional ground surface displacements from 20 m long static pipe-bursting experiments are reported. These experiments were conducted with firm-to-stiff clay backfill in a trench with very stiff clay sidewalls at three different burial depths. Multiple digital cameras and image analysis were used to quantify the surface response as the expander progressed through the original pipe. The experiments quantified the upward surface movement as the expander approached, the effect of burial depth on maximum uplift, and the final amount of uplift after it decreased to a residual displacement. The experiments also quantified the axially forward ground surface movement as the expander approached, reaching maximum just ahead of the expander, and decreasing to almost zero after the expander had passed by. Lateral movements of the ground surface away from the centreline are also reported, which were essentially zero at the centre line, increasing to a maximum and then decreasing with distance from the centreli.
Racial disparity in utilization of therapeutic modalities among multiple myeloma patients: a SEER‐medicare analysis

Outcomes have improved considerably in multiple myeloma (MM), but disparities among racial‐ethnic groups exist. Differences in utilization of novel therapeutics are likely contributing factors. We explored such differences from the SEER‐Medicare database. A utilization analysis of lenalidomide, thalidomide, bortezomib, and stem cell transplant (SCT) was performed for patients diagnosed with MM between 2007 and 2009, including use over time, use by race, time‐dependent trends for each racial subgroup, and survival analysis. A total of 5338 MM patients were included with median 2.4‐year follow‐up. Within the first year of MM diagnosis, utilization of lenalidomide, bortezomib, SCT, and more than one novel agent increased over time while utilization of thalidomide decreased. There was significantly lower utilization of lenalidomide among African‐Americans (P < 0.01), higher thalidomide use among Hispanics and Asians (P < 0.01), and lower bortezomib use among Asians (P < 0.01). Hispanics had the highest median number of days to first dose of bortezomib (P = 0.02) and the lowest utilization of SCT (P < 0.01). Hispanics and Asians were the only groups without notable increases in lenalidomide and bortezomib use, respectively. SCT utilization increased over time for all except African‐Americans. SCT use within the first year after diagnosis was associated with better overall survival (HR 0.52; 95% CI: 0.4–0.68), while bortezomib use was associated with inferior survival (HR 1.14; 95% CI 1.02–1.28). We noted considerable variability in MM therapeutics utilization with seeming inequity for racial‐ethnic minorities. These trends should be considered to eliminate drug access and utilization disparities and achieve equitable benefit of therapeutic advances across all races.