LLukas22/scidocs huggingface dataset:
A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors.

BACKGROUND
AT7519 is an inhibitor of multiple cyclin-dependent kinases (CDKs). Based on potent antitumor activity in preclinical models, a first-in-human clinical trial in refractory solid tumors investigated its safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD).


PATIENTS AND METHODS
AT7519 was administered in a '3 + 3' dose- escalation scheme on 5 consecutive days every 3 weeks to patients with advanced, refractory solid tumors. Samples to monitor AT7519 PK and PD were obtained.


RESULTS
Twenty-eight patients were treated at seven dose levels (1.8-40 mg/m(2)/day). At 40 mg/m(2)/day, one patient developed hypotension and ST segment elevation. At 34 mg/m(2)/day, dose-limiting toxic effects (DLTs) were QTc prolongation with one death (grade 5), fatigue (grade 4) and mucositis (grade 3). Electrocardiogram review suggested a dose-dependent increase in QTc and recruitment was discontinued without establishing a maximum tolerated dose. Four patients exhibited stable disease for >6 months and one had a prolonged partial response. PK profile revealed modest interpatient variation with linear exposure at increasing doses. Inhibition of markers of CDK activity was observed across the dose range and manifested in antiproliferative activity at a dose of 28 mg/m(2).


CONCLUSION
AT7519 elicited clinical and PD activity resulting from CDK inhibition at doses below the appearance of DLT of QTc prolongation.
One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis.

BACKGROUND
Since the use of parathyroid hormone as a treatment for osteoporosis is limited to two years or less, the question of whether antiresorptive therapy should follow parathyroid hormone therapy is important. We previously reported results after the first year of this randomized trial comparing the use of full-length parathyroid hormone (1-84) alone, alendronate alone, or both combined. In the continuation of this trial, we asked whether antiresorptive therapy is required to maintain gains in bone mineral density after one year of therapy with parathyroid hormone (1-84).


METHODS
In the data reported here, women who had received parathyroid hormone (1-84) monotherapy (100 microg daily) in year 1 were randomly reassigned to one additional year with either placebo (60 subjects) or alendronate (59 subjects). Subjects who had received combination therapy in year 1 received alendronate in year 2; those who had received alendronate monotherapy in year 1 continued with alendronate in year 2. Bone mineral density at the spine and hip was assessed with the use of dual-energy x-ray absorptiometry and quantitative computed tomography (CT).


RESULTS
Over two years, alendronate therapy after parathyroid hormone therapy led to significant increases in bone mineral density in comparison with the results for placebo after parathyroid hormone therapy, a difference particularly evident for bone mineral density in trabecular bone at the spine on quantitative CT (an increase of 31 percent in the parathyroid hormone-alendronate group as compared with 14 percent in the parathyroid hormone-placebo group). During year 2, subjects receiving placebo lost substantial bone mineral density.


CONCLUSIONS
After one year of parathyroid hormone (1-84), densitometric gains appear to be maintained or increased with alendronate but lost if parathyroid hormone is not followed by an antiresorptive agent. These results have clinical implications for therapeutic choices after the discontinuation of parathyroid hormone.
World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects.

Abstract These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia published in 2006. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful. They are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A-F) and five levels of recommendation (1-5) ( Bandelow et al. 2008a ,b, World J Biol Psychiatry 9:242, see Table 1 ). This second part of the updated guidelines covers long-term treatment as well as the management of relevant side effects. These guidelines are primarily concerned with the biological treatment (including antipsychotic medication and other pharmacological treatment options) of adults suffering from schizophrenia.
INTELLIGENT VIDEO SURVEILLANCE SYSTEM ARCHITECTURE FOR ABNORMAL ACTIVITY DETECTION

Video security is becoming more and more vital today due to rapid development of hardware equipments as the number of installed cameras can confirm. This paper presents the system architecture of IVSS, an Intelligent Video Surveillance System based on IPcameras and deployed in an academic environment. In fact, Video surveillance is increasingly found in academic institutions. It is used to oversee the safety of teachers and students, as well as to protect assets from vandalism and theft. In this work the surveillance system is deployed in our university environment, it is based on a set of digital IP video cameras linked by the university IP network infrastructure. Our system architecture is based on efficient moving object detecting and tracking algorithm and a robust statistical activity recognition framework based on SVM which is used for modeling activities. The experimental results on real-time video streams show the feasibility of our system and its effectiveness in human activity recognition.
MC1R gene mutation and its association with oculocutaneous albinism type (OCA) phenotype in a consanguineous Pakistani family.

[2] Brown SJ, McLean WH. One remarkable molecule: filaggrin. J Invest Dermatol 2012;132:751–62. [3] Sandilands A, Terron-Kwiatkowski A, Hull PR, O’Regan GM, Clayton TH, Watson RM, et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet 2007;39:650–4. [4] Margolis DJ, Apter AJ, Gupta J, Hoffstad O, Papadopoulos M, Campbell LE, et al. The persistence of atopic dermatitis and Filaggrin mutations in a US longitudinal cohort. J Allergy Clin Immunol 2012;130(4):912–7. [5] Smith FJ, Irvine AD, Terron-Kwiatkowski A, Sandilands A, Campbell LE, Zhao Y, et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 2006;38:337–42. [6] Paternoster L, Standl M, Chen CM, Ramasamy A, Bonnelykke K, Duijts L, et al. Meta-analysis of genome-wide association studies identifies three new risk Table 1 Reliability and validity comparisons for FLG null mutations as assayed by TaqMan and beadchip methods.
A comparative phase 1 clinical trial to identify anti-infective mechanisms of vitamin D in people with HIV infection

OBJECTIVES
To determine if there is a biological mechanism that explains the association between HIV disease progression and increased mortality with low circulating vitamin D levels; specifically, to determine if restoring vitamin D levels induced T-cell functional changes important for antiviral immunity.


DESIGN
This was a pilot, open-label, three-arm prospective phase 1 study.


METHODS
We recruited 28 patients with low plasma vitamin D (<50 nmol/l 25-hydroxyvitamin D3), comprising 17 HIV+ patients (11 on HAART, six treatment-naive) and 11 healthy controls, who received a single dose of 200 000 IU oral cholecalciferol. Advanced T-cell flow cytometry methods measured CD4 T-cell function associated with viral control in blood samples at baseline and 1-month after vitamin D supplementation.


RESULTS
One month of vitamin D supplementation restored plasma levels to sufficiency (>75 nmol/l) in 27 of 28 patients, with no safety issues. The most striking change was in HIV+ HAART+ patients, where increased frequencies of antigen-specific T cells expressing macrophage inflammatory protein (MIP)-1β - an important anti-HIV blocking chemokine - were observed, with a concomitant increase in plasma MIP-1β, both of which correlated significantly with vitamin D levels. In addition, plasma cathelicidin - a vitamin D response gene with broad antimicrobial activity - was enhanced.


CONCLUSION
Vitamin D supplementation modulates disease-relevant T-cell functions in HIV-infected patients, and may represent a useful adjunct to HAART therapy.
Facilitating Management Learning Developing Critical Reflection Through Reflective Tools

The aim of this article is to explore how the practice of critical reflection within a management learning process can be facilitated through the application of reflective processes and tools. A distinction is drawn between reflection as a form of individual development (of, say, the reflective practitioner), and critical reflection as a route to collective action and a component of organizational learning and change. Critical reflection, however, is not a process that comes naturally to many managers and may have to be learned or facilitated, either in formal classroom contexts, or through learning processes such as coaching, mentoring and action learning. The article discusses some of the tools available to learning facilitators, in helping a group or client towards a more critically reflective understanding of their situation and organization. These include processes such as storytelling, and reflective and reflexive conversations, and the use of tools such as reflective metaphors, critical incident analysis, reflective journals, repertory grids and concept mapping. Such tools provide an aid to critical reflection, which is seen as one process that mediates between experience, knowledge and action.
Stator Winding Thermal Conductivity Evaluation: An Industrial Production Assessment

The thermal conductivity between winding and lamination is one of the most critical parameters in electrical machine thermal analysis. Its value depends on the insulation material and on the manufacturing process of the winding system, and for this reason cannot be computed using analytical equations. In this paper, a practical investigation of equivalent thermal conductivity of electrical machines stator winding is presented and discussed. The fully experimental approach is based on a fast transient thermal test to evaluate the winding equivalent thermal conductivity. The test campaign is carried out on two sets of Total Enclosed Fan Cooled (TEFC) industrial induction motors produced by two different manufacturers; the rated power of the devices under test ranges from 1.5 to 55 kW.
An analog bionic ear processor with zero-crossing detection

A 75 dB 251 /spl mu/W analog speech processor is described that preserves the performance, robustness, and programmability needed for deaf patients at a reduced power consumption compared to that of implementations with A/D and DSP. It also provides zero-crossing outputs for stimulation strategies that use phase information to improve performance.
Can You Be Persuaded? Individual Differences in Susceptibility to Persuasion

Persuasive technologies are growing in popularity and many designers create systems which intentionally change users attitudes or behaviors. This study shows that peoples individual differences in susceptibility to persuasion, as implemented using the six persuasion principles proposed by Cialdini [2], relates to their compliance to a persuasive request which is accompanied by a persuasive cue. This result is a starting point for designers to start incorporating individual differences in susceptibility to persuasive cues in their adaptive persuasive systems.
Effect of single-dose anthelmintic treatment during pregnancy on an infant's response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial

BACKGROUND
Helminth infections affect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections affects development of an infant's immune response to immunisations and unrelated infections.


METHODS
In this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computer-generated random number sequence in blocks of 100, we assigned patients to 440 mg albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole-matching placebo (n=626), or an albendazole-matching placebo and praziquantel-matching placebo (n=628). All participants and hospital staff were masked to allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus, and measles immunisation; incidence of infectious diseases during infancy; and vertical HIV transmission. Analysis was by intention-to-treat. This trial is registered, number ISRCTN32849447.


FINDINGS
Data were available at delivery for 2356 women, with 2345 livebirths; 2115 (90%) of liveborn infants remained in follow-up at 1 year of age. Neither albendazole nor praziquantel treatments affected infant response to BCG, tetanus, or measles immunisation. However, in infants of mothers with hookworm infection, albendazole treatment reduced interleukin-5 (geometric mean ratio 0·50, 95% CI 0·30-0·81, interaction p=0·02) and interleukin-13 (0·52, 0·34-0·82, 0·0005) response to tetanus toxoid. The rate per 100 person-years of malaria was 40·9 (95% CI 38·3-43·7), of diarrhoea was 134·1 (129·2-139·2), and of pneumonia was 22·3 (20·4-24·4). We noted no effect on infectious disease incidence for albendazole treatment (malaria [hazard ratio 0·95, 95% CI 0·79-1.14], diarrhoea [1·06, 0·96-1·16], pneumonia [1·11, 0·90-1·38]) or praziquantel treatment (malaria [1·00, 0·84-1·20], diarrhoea [1·07, 0·98-1·18], pneumonia [1·00, 0·80-1·24]). In HIV-exposed infants, 39 (18%) were infected at 6 weeks; vertical transmission was not associated with albendazole (odds ratio 0·70, 95% CI 0·35-1·42) or praziquantel (0·60, 0·29-1·23) treatment.


INTERPRETATION
These results do not accord with the recently advocated policy of routine antenatal anthelmintic treatment, and the value of such a policy may need to be reviewed.


FUNDING
Wellcome Trust.
Two-Stage Approach for Detection and Reduction of Motion Artifacts in Photoplethysmographic Data

Corruption of photopleythysmograms (PPGs) by motion artifacts has been a serious obstacle to the reliable use of pulse oximeters for real-time, continuous state-of-health monitoring. In this paper, we propose an automated, two-stage PPG data processing method to minimize the effects of motion artifacts. The technique is based on our prior work related to motion artifact detection (stage 1) [R. Krishnan, B. Natarajan, and S. Warren, ``Analysis and detection of motion artifacts in photoplethysmographic data using higher order statistics,'' in Proc. IEEE Int. Conf. Acoust., Speech, Signal Process. (ICASSP 2008), Las Vegas, Nevada, Apr. 2008, pp. 613-616] and motion artifact reduction (stage 2) [R. Krishnan, B. Natarajan, and S. Warren, ``Motion artifact reduction in photoplethysmography using magnitude-based frequency domain independent component analysis,'' in Proc. 17th Int. Conf. Comput. Commun. Network, St. Thomas, Virgin Islands, Aug. 2008, pp. 1-5]. Regarding stage 1, we present novel and consistent techniques to detect the presence of motion artifact in PPGs given higher order statistical information present in the data. We analyze these data in the time and frequency domains (FDs) and identify metrics to distinguish between clean and motion-corrupted data. A Neyman-Pearson detection rule is formulated for each of the metrics. Furthermore, by treating each of the metrics as observations from independent sensors, we employ hard fusion and soft fusion techniques presented in [Z. Chair and P. Varshney, ``Optimal data fusion in multiple sensor detection systems,'' IEEE Trans. Aerosp. Electron. Syst., AES, vol. 1, no. 1, pp. 98-101, Jan. 1986] and [C. C. Lee and J. J. Chao, ``Optimum local decision space partitioning for distributed detection,'' IEEE Trans. Aerosp. Electron. Syst., AES, vol. 25, no. 7, pp. 536-544, Jul. 1989], respectively, in order to fuse individual decisions into a global system decision. For stage two, we propose a motion artifact reduction method that is effective even in the presence of severe subject movement. The approach involves an enhanced preprocessing unit consisting of a motion detection unit (MDU, developed in this paper), period estimation unit, and Fourier series reconstruction unit. The MDU identifies clean data frames versus those corrupted with motion artifacts. The period estimation unit determines the fundamental frequency of a corrupt frame. The Fourier series reconstruction unit reconstructs the final preprocessed signal by utilizing the spectrum variability of the pulse waveform. Preprocessed data are then fed to a magnitude-based FD independent component analysis unit. This helps reduce motion artifacts present at the frequencies of the reconstruction components. Experimental results are presented to demonstrate the efficacy of the overall motion artifact reduction method.
A Smart Home is No Castle: Privacy Vulnerabilities of Encrypted IoT Traffic

The increasing popularity of specialized Internetconnected devices and appliances, dubbed the Internet-of-Things (IoT), promises both new conveniences and new privacy concerns. Unlike traditional web browsers, many IoT devices have always-on sensors that constantly monitor fine-grained details of users’ physical environments and influence the devices’ network communications. Passive network observers, such as Internet service providers, could potentially analyze IoT network traffic to infer sensitive details about users. Here, we examine several commercially-available IoT smart home devices and find that their network traffic rates reveal potentially sensitive user interactions even when the traffic is encrypted. These results suggest technical approaches for protecting IoT device owner privacy and indicate that IoT-specific concerns must be considered in the ongoing policy debate around ISP data collection and usage.
Limited impact of a multicenter intervention to improve the quality and efficiency of pneumonia care.

STUDY OBJECTIVES
To evaluate the impact of a multifactorial intervention to improve the quality, efficiency, and patient understanding of care for community-acquired pneumonia.


DESIGN
Times series cohort study.


SETTING
Four academic health centers in the New York City metropolitan area.


PATIENTS OR PARTICIPANTS
All consecutive adults hospitalized for pneumonia during a 5-month period before (n = 1,013) and after (n = 1,081) implementation of an inpatient quality improvement (QI) initiative.


INTERVENTIONS
A multidisciplinary team of opinion leaders developed evidence-based treatment guidelines and critical pathways, conducted educational sessions with physicians, distributed pocket reminder cards, promoted standardized orders, and developed bilingual patient education materials.


MEASUREMENTS AND RESULTS
The average age was 71.4 years, and 44.1% of cases were low risk, 36.8% were moderate risk, and 19.2% were high risk. The preintervention and postintervention groups were well matched on age, sex, race, nursing home residence, pneumonia severity, initial presentation, and most major comorbidities. The intervention increased the use of guideline-recommended antimicrobial therapy from 78.1 to 83.4% (p = 0.003). There was also a borderline decrease in the proportion of patients being discharged prior to becoming clinically stable, from 27.0 to 23.5% (p = 0.06). However, there were no improvements in the other targeted indicators, including time to first dose of antibiotics, proportion receiving antibiotics within 8 h, timely switch to oral antibiotics, timely discharge, length of stay, or patient education outcomes.


CONCLUSIONS
This real-world QI program was able to improve modestly on some quality indicators, but not effect resource use or patient knowledge of their disease. Changing physician and organizational behavior in academic health centers will require the development and implementation of more intensive, system-oriented strategies.
The Rainbow Scale for Assessing Breast Ptosis: Validation of Three Different Views.

BACKGROUND
Photographic scales have become an increasingly used tool in objectively assessing outcomes in aesthetic surgery. However, no online photographic scale for assessing breast ptosis has been developed yet that is readily available.


OBJECTIVES
This study was designed to validate the online Rainbow Scale for the assessment of breast ptosis for the anterior-posterior (AP), lateral, and oblique views.


METHODS
For the five grades of the Rainbow Scale format, standardized reference photographs were selected. Six plastic surgeons rated 15 photographs for each view three times. Intra- and inter-observer agreements were calculated by using the weighted kappa coefficient and differences in intra- and inter-observer agreements between the three views were assessed for statistical significance using the Kruskal-Wallis test.


RESULTS
The mean intra-observer agreements were 0.91 (range, 0.82-0.98) for the AP view, 0.88 (range, 0.77-1.00) for the oblique view, and 0.86 (range, 0.74-0.97) for the lateral view and did not vary significantly between all three views. The mean inter-observer agreements were 0.88 (range, 0.77-0.95) for the AP view, 0.84 (range, 0.72-0.94) for the oblique view, and 0.82 (range, 0.58-0.95) for the lateral view. The mean inter-observer agreements of the AP view varied significantly from the oblique view (P = .012) and the lateral view (P = .001).


CONCLUSIONS
The Rainbow Scale for breast ptosis has been validated for the AP view, the lateral view, and the oblique view and is reproducible and reliable for the assessment of breast ptosis in three different views in an online setup.


LEVEL OF EVIDENCE
4 Diagnostic.
A monovalent streptavidin with a single femtomolar biotin binding site

Streptavidin and avidin are used ubiquitously because of the remarkable affinity of their biotin binding, but they are tetramers, which disrupts many of their applications. Making either protein monomeric reduces affinity by at least 104-fold because part of the binding site comes from a neighboring subunit. Here we engineered a streptavidin tetramer with only one functional biotin binding subunit that retained the affinity, off rate and thermostability of wild-type streptavidin. In denaturant, we mixed a streptavidin variant containing three mutations that block biotin binding with wild-type streptavidin in a 3:1 ratio. Then we generated monovalent streptavidin by refolding and nickel-affinity purification. Similarly, we purified defined tetramers with two or three biotin binding subunits. Labeling of site-specifically biotinylated neuroligin-1 with monovalent streptavidin allowed stable neuroligin-1 tracking without cross-linking, whereas wild-type streptavidin aggregated neuroligin-1 and disrupted presynaptic contacts. Monovalent streptavidin should find general application in biomolecule labeling, single-particle tracking and nanotechnology.