A comprehensible SOM-based scoring system.

The significant growth of consumer credit has resulted in a wide range of statistical and non-statistical methods for classifying applicants in 'good' and 'bad' risk categories. Traditionally, (logistic) regression used to be one of the most popular methods for this task, but recently some newer techniques like neural networks and support vector machines have shown excellent classification performance. Self-organizing maps (SOMs) have existed for decades and although they have been used in various application areas, only little research has been done to investigate their appropriateness for credit scoring. In this paper, it is shown how a trained SOM can be used for classification and how the basic SOM-algorithm can be integrated with supervised techniques like the multi-layered perceptron. Classification accuracy of the models is benchmarked with results reported previously.Decision; Knowledge; Knowledge discovery; Systems; Growth; Credit; Methods; Risk; Regression; Neural networks; Networks; Classification; Performance; Area; Research; Credit scoring; Models; Model;

Targeting Chromatin Complexes in Myeloid Malignancies and Beyond: From Basic Mechanisms to Clinical Innovation

The aberrant function of chromatin regulatory networks (epigenetics) is a hallmark of cancer promoting oncogenic gene expression. A growing body of evidence suggests that the disruption of specific chromatin-associated protein complexes has therapeutic potential in malignant conditions, particularly those that are driven by aberrant chromatin modifiers. Of note, a number of enzymatic inhibitors that block the catalytic function of histone modifying enzymes have been established and entered clinical trials. Unfortunately, many of these molecules do not have potent single-agent activity. One potential explanation for this phenomenon is the fact that those drugs do not profoundly disrupt the integrity of the aberrant network of multiprotein complexes on chromatin. Recent advances in drug development have led to the establishment of novel inhibitors of protein–protein interactions as well as targeted protein degraders that may provide inroads to longstanding effort to physically disrupt oncogenic multiprotein complexes on chromatin. In this review, we summarize some of the current concepts on the role epigenetic modifiers in malignant chromatin states with a specific focus on myeloid malignancies and recent advances in early-phase clinical trials

Stratospheric OClO and NO2 measured by groundbased UV/Vis-spectroscopy in Greenland in January and February 1990 and 1991

Groundbased UV/Vis-spectroscopy of zenith scattered sunlight was performed at Sondre Stromfjord (Greenland) during Jan/Feb 1990 and Jan/Feb 1991. Considerable amounts of OClO were observed during both campaigns. Maximum OClO vertical column densities at 92 deg solar zenith angle (SZA) were 7.4 x 10(exp 13) molec/sq cm in 1990 and 5.7 x 10(exp 13) molec/sq cm in 1991 (chemical enhancement is included in the calculation of the air mass factor (AMF)). A threshold seems to exist for OClO detection: OClO was detected on every day when the potential vorticity at the 475 K level of potential temperature was higher than 35 x 10(exp -6)Km(exp 2)kg(exp -1)s(exp -1). NO2 vertical columns lower than 1 x 10(exp 15) molec/sq cm were frequently observed in both winters

Mice Transgenic for the Human Carcinoembryonic Antigen Gene Maintain Its Spatiotemporal Expression Pattern

The tumor marker carcinoembryonic antigen (CEA) is predominantly expressed in epithelial cells along the gastrointestinal tract and in a variety of adenocarcinomas. As a basis for investigating its in vivo regulation and for establishing an animal model for tumor immunotherapy, transgenic mice were generated with a 33-kilobase cosmid clone insert containing the complete human CEA gene and flanking sequences. CEA was found in the tongue, esophagus, stomach, small intestine, cecum, colon, and trachea and at low levels in the lung, testis, and uterus of adult mice of independent transgenic strains. CEA was first detected at day 10.5 of embryonic development (embryonic day 10.5) in primary trophoblast giant cells and was found in the developing gut, urethra, trachea, lung, and nucleus pulposus of the vertebral column from embryonic day 14.5 onwards. From embryonic day 16.5 CEA was also visible in the nasal mucosa and tongue. Because this spatiotemporal expression pattern correlates well with that known for humans, it follows that the transferred genomic region contains all of the regulatory elements required for the correct expression of CEA. Furthermore, although mice apparently lack an endogenous CEA gene, the entire repertoire of transcription factors necessary for correct expression of the CEA transgene is conserved between mice and humans. After tumor induction, these immunocompetent mice will serve as a model for optimizing various forms of immunotherapy, using CEA as a target antigen

Human prostate sphere-forming cells represent a subset of basal epithelial cells capable of glandular regeneration in vivo.

BackgroundProstate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these cells may have therapeutic implications. Cells from dissociated tissues that form spheres in vitro often represent stem/progenitor cells. A subset of human prostate cells that form prostaspheres were evaluated for self-renewal and tissue regeneration capability in the present study.MethodsProstaspheres were generated from 59 prostatectomy specimens. Lineage marker expression and TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in situ hybridization (FISH). Subpopulations of prostate epithelial cells were isolated by cell sorting and interrogated for sphere-forming activity. Tissue regeneration potential was assessed by combining sphere-forming cells with rat urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice.ResultsProstate tissue specimens were heterogeneous, containing both benign and malignant (Gleason 3-5) glands. TMPRSS-ERG fusion was found in approximately 70% of cancers examined. Prostaspheres developed from single cells at a variable rate (0.5-4%) and could be serially passaged. A basal phenotype (CD44+CD49f+CK5+p63+CK8-AR-PSA-) was observed among sphere-forming cells. Subpopulations of prostate cells expressing tumor-associated calcium signal transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo implantation of sphere-forming cells and rUGSM regenerated tubular structures containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in prostaspheres derived from fusion-positive tumor tissue, suggesting a survival/growth advantage of benign prostate epithelial cells.ConclusionHuman prostate sphere-forming cells self-renew, have tissue regeneration capability, and represent a subpopulation of basal cells

Children's suggestibility in relation to their understanding about sources of knowledge

In the experiments reported here, children chose either to maintain their initial belief about an object's identity or to accept the experimenter's contradicting suggestion. Both 3– to 4–year–olds and 4– to 5–year–olds were good at accepting the suggestion only when the experimenter was better informed than they were (implicit source monitoring). They were less accurate at recalling both their own and the experimenter's information access (explicit recall of experience), though they performed well above chance. Children were least accurate at reporting whether their final belief was based on what they were told or on what they experienced directly (explicit source monitoring). Contrasting results emerged when children decided between contradictory suggestions from two differentially informed adults: Three– to 4–year–olds were more accurate at reporting the knowledge source of the adult they believed than at deciding which suggestion was reliable. Decision making in this observation task may require reflective understanding akin to that required for explicit source judgments when the child participates in the task

Comparison of routes for achieving parenteral access with a focus on the management of patients with Ebola virus disease.

Dehydration is an important cause of death in patients with Ebola virus disease (EVD). Parenteral fluids are often required in patients with fluid requirements in excess of their oral intake. The peripheral intravenous route is the most commonly used method of parenteral access, but inserting and maintaining an intravenous line can be challenging in the context of EVD. Therefore it is important to consider the advantages and disadvantages of different routes for achieving parenteral access (e.g. intravenous, intraosseous, subcutaneous and intraperitoneal). To compare the reliability, ease of use and speed of insertion of different parenteral access methods. We ran the search on 17 November 2014. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, Ovid MEDLINE(R) and Ovid OLDMEDLINE(R), Embase Classic + Embase (OvidSP), CINAHL (EBSCOhost), clinicaltrials.gov and screened reference lists. Randomised controlled trials comparing different parenteral routes for the infusion of fluids or medication. Two review authors examined the titles and abstracts of records obtained by searching the electronic databases to determine eligibility. Two review authors extracted data from the included trials and assessed the risk of bias. Outcome measures of interest were success of insertion; time required for insertion; number of insertion attempts; number of dislodgements; time period with functional access; local site reactions; clinicians' perception of ease of administration; needlestick injury to healthcare workers; patients' discomfort; and mortality. For trials involving the administration of fluids we also collected data on the volume of fluid infused, changes in serum electrolytes and markers of renal function. We rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach for the following outcomes: success of insertion, time required for insertion, number of dislodgements, volume of fluid infused and needlestick injuries. We included 17 trials involving 885 participants. Parenteral access was used to infuse fluids in 11 trials and medications in six trials. None of the trials involved patients with EVD. Intravenous and intraosseous access was compared in four trials; intravenous and subcutaneous access in 11; peripheral intravenous and intraperitoneal access in one; saphenous vein cutdown and intraosseous access in one; and intraperitoneal with subcutaneous access in one. All of the trials assessing the intravenous method involved peripheral intravenous access.We judged few trials to be at low risk of bias for any of the assessed domains.Compared to the intraosseous group, patients in the intravenous group were more likely to experience an insertion failure (risk ratio (RR) 3.89, 95% confidence interval (CI) 2.39 to 6.33; n = 242; GRADE rating: low). We did not pool data for time to insertion but estimates from the trials suggest that inserting intravenous access takes longer (GRADE rating: moderate). Clinicians judged the intravenous route to be easier to insert (RR 0.15, 95% CI 0.04 to 0.61; n = 182). A larger volume of fluids was infused via the intravenous route (GRADE rating: moderate). There was no evidence of a difference between the two routes for any other outcomes, including adverse events.Compared to the subcutaneous group, patients in the intravenous group were more likely to experience an insertion failure (RR 14.79, 95% CI 2.87 to 76.08; n = 238; GRADE rating: moderate) and dislodgement of the device (RR 3.78, 95% CI 1.16 to 12.34; n = 67; GRADE rating: low). Clinicians also judged the intravenous route as being more difficult to insert and patients were more likely to be agitated in the intravenous group. Patients in the intravenous group were more likely to develop a local infection and phlebitis, but were less likely to develop erythema, oedema or swelling than those in the subcutaneous group. A larger volume of fluids was infused into patients via the intravenous route. There was no evidence of a difference between the two routes for any other outcome.There were insufficient data to reliably determine if the risk of insertion failure differed between the saphenous vein cutdown (SVC) and intraosseous method (RR 4.00, 95% CI 0.51 to 31.13; GRADE rating: low). Insertion using SVC took longer than the intraosseous method (MD 219.60 seconds, 95% CI 135.44 to 303.76; GRADE rating: moderate). There were no data and therefore there was no evidence of a difference between the two routes for any other outcome.There were insufficient data to reliably determine the relative effects of intraperitoneal or central intravenous access relative to any other parenteral access method. There are several different ways of achieving parenteral access in patients who are unable meet their fluid requirements with oral intake alone. The quality of the evidence, as assessed using the GRADE criteria, is somewhat limited because of the lack of adequately powered trials at low risk of bias. However, we believe that there is sufficient evidence to draw the following conclusions: if peripheral intravenous access can be achieved easily, this allows infusion of larger volumes of fluid than other routes; but if this is not possible, the intraosseous and subcutaneous routes are viable alternatives. The subcutaneous route may be suitable for patients who are not severely dehydrated but in whom ongoing fluid losses cannot be met by oral intake.A film to accompany this review can be viewed here (http://youtu.be/ArVPzkf93ng)