LLukas22/scidocs huggingface dataset:
Validation of analytical methods used in cleaning validation

15 The information used to establish a positive cleaning validation is based on the result of validated analytical measurements. There must be a high degree of confidence in these results, as human safety depends on the lack of residues remaining on equipment. This article will describe various aspects regarding the validation of analytical methods used in cleaning validations. The validation elements are explored from both a theoretical point of view and through examples. References are provided to guide the reader to more in-depth information. A n analytical method is one of the deciding factors in establishing the cleanliness of pharmaceutical manufacturing equipment. It is, therefore, important that there be a high level of confidence in the results obtained using the method. This high level of confidence is established by testing and defining the usefulness of the analytical method. A properly developed cleaning validation strategy includes the analytical method validation, which defines the method parameters necessary in providing a high level of confidence in the cleaning results. The analytical method validation study demonstrates to scientific staffs, manufacturing personnel, and regulatory agencies, that the method performs as required, and that the results are reliable. There are many articles available that address analytical method validation within and outside of the pharmaceutical industry, both domestically and worldwide. Personnel other than analytical chemists may not understand the need for analytical method validation, let alone the extent to which these methods need to be evaluated. They may not understand that analytical method validation, as well as cleaning validation, has an important impact on everyday pharmaceutical manufacturing. 9 As is the case with cleaning validation, analytical methods may need to be revalidated. 10 This revalidation may arise from changes in in-strumentation, analytes or manufacturing methods, or cleaning processes that affect the ability of the analytical method to determine the correct analyte level. Measuring cleanliness is a difficult task. Essentially, trace residues on surfaces are the target analytes. The residue must first be extracted from a surface, recovered from the extraction medium, and then suitably quantitated. Residue analysis is quite different from analyzing bulk or formulated drug ac-tives, as obtainable precisions and accuracies may be larger than the analyst is accustomed. Sensitivity levels of the techniques employed need to be considered for linearity, precision , and accuracy. The first decision to be made is the decision as to which residue will be measured. This residue could be the …
Couple-Oriented Education and Support Intervention for Osteoarthritis: Effects on Spouses' Support and Responses to Patient Pain.

The purpose of this study was to determine whether a couple-oriented education and support intervention for osteoarthritis was more efficacious than a similar patient-oriented intervention in terms of enhancing spouses' support of patients and their positive and negative responses to patient pain. Repeated-measures analyses of covariance with the completers sample (N = 103 dyads) showed that at the postintervention assessment, patients in the couple-oriented intervention reported a greater decrease in their spouses' punishing responses (e.g., anger, irritation) than did patients in the patient-oriented intervention. In addition, a trend effect was observed in regard to the advantage of couple-oriented intervention for increasing spouses' attempts to distract patients from their pain. At the 6-month follow-up, patients in the couple-oriented intervention reported greater increased spouse support than those in the patient-oriented intervention. Findings illustrate the value of examining change in specific types of marital interactions targeted in a couples intervention, and the need to strengthen the impact of future couple-oriented interventions.
Essays and English Traits

grounds. But they give a voice to the class who, at the moment, take the lead; and they have an instinct for finding where the power now lies, which is eternally shifting its banks. Sympa­ thizing with and speaking for the class that rules the hour, yet being apprised of every ground-swell, every Chartist resolution, every Church squabble, every strike in the mills, they detect the first tremblings of change. They watch the hard and bitter struggles of the authors of each liberal movement, year by year,—watching them only to taunt and obstruct them,—until, at last, when they see that these have established their fact, that power is on the point of passing to them,—they strike in, with the voice of a monarch, astonish those whom they succor, as much as those whom they desert, and make victory sure. O f course, the aspirants see that the "Times" is one of the goods of fortune, not to be won but by winning their cause. "Punch" is equally an expression of English good sense, as the "London Times ." It is the comic version of the same sense. Many of its caricatures are equal to the best pamphlets, and will convey to the eye in an instant the popular view which was taken of each turn of public affairs. Its sketches are usually made by masterly hands, and sometimes with genius; the delight of every class, because uniformly guided by that taste which is tyrannical in England. It is a new trait of the nineteenth century that the wit and humor of England, as in Punch, so in the humorists, Jerrold, Dickens, Thack­ eray, Hood, have taken the direction of humanity and freedom. T h e "Times ," like every important institution, shows the way to a better. It is a l iving index of the colossal British power. Its existence honors the people who dare to print all they know, dare to know all the facts, and do not wish to be flattered by hiding the extent of the public disaster. There is always safety in valor. I wish I could add that this journal aspired to deserve the power it wields, by guidance of the public sentiment to the right. It is usually pretended, in Parliament and elsewhere, that the English press has a high tone, —which it has not. It has an imperial tone as of a powerful and independent nation. But as with other empires, its tone is prone to be official, and even officinal. T h e " T i m e s " shares all the limitadons of the governing classes, and wishes never to be in a minority. If
Job satisfaction among nurses in a hospital.

BACKGROUND
Nursing is one of the stressful jobs in health sector. The level of job satisfaction in the profession remains a matter of concern. This study means to explore the job satisfaction among the nurses of Dhulikhel Hospital.


METHODS
A Descriptive cross sectional study design was conducted in Dhulikhel Hospital; a community based Hospital of Nepal Health Research Council from January to December 2009. All the nursing staffs that consented to the study filled up a standard questionnaire.


RESULTS
A total of 85 nurses completed the study. The mean age of the respondents' was 23. 80.6% of the nursing staffs were satisfied. "Being considered a resource of health" provided highest sense of satisfaction, while "Lack of opportunities for further education and training" provided lowest sense of satisfaction.


CONCLUSIONS
Majority of the nurses were satisfied with their present condition of work. Since job satisfaction is a dynamic process, the result may not be static or consistence. Working environment and employees expectations should receive attention.
Evaluation of breakdown characteristics of gas insulated switchgears for non-standard lightning impulse waveforms - method for converting non-standard lightning impulse waveforms into standard lightning impulse waveforms -

To lower the lightning impulse withstand voltage of gas insulated switchgear (GIS) while maintaining the high reliability of its insulation performance, it is important to define in an organized way the insulation characteristics for non-standard lightning impulse voltage waveforms that represent actual surge waveforms in the field and compare them with the characteristics for the standard lightning impulse waveform quantitatively. In the preceding researches, lightning surge waveforms and disconnector switching surge waveforms at UHV, 500 kV, and 275 kV substations were analyzed and five to six kinds of non-standard lightning impulse waveforms with basic frequencies of 0.6 to 5.0 MHz were identified. Then, the dielectric breakdown voltage iquest time characteristics were measured under several different conditions on the quasi-uniform SF6 gas gaps and partly the coneshaped insulating spacers that represent insulation elements of GIS for six kinds of nonstandard lightning impulse waveforms. In this paper, the resultant breakdown voltages were evaluated in terms of the overvoltage duration, which led to their formulation in a unified way. On the basis of these insulation characteristics and their unified formulation, the paper investigated a method for converting non-standard lightning impulse waveforms into standard lightning impulse waveforms with equivalent stress for the insulation. When the constructed algorithm was applied to five examples of representative two type waveforms in the lightning surge time region, they were converted into standard lightning impulse waveforms with crest values reduced by 20% to 34%, suggesting potentiality for reduction of lightning impulse insulation specifications of GIS.
Autonomous and controlled motivational regulations for multiple health-related behaviors: between- and within-participants analyses

Self-determination theory has been applied to the prediction of a number of health-related behaviors with self-determined or autonomous forms of motivation generally more effective in predicting health behavior than non-self-determined or controlled forms. Research has been confined to examining the motivational predictors in single health behaviors rather than comparing effects across multiple behaviors. The present study addressed this gap in the literature by testing the relative contribution of autonomous and controlling motivation to the prediction of a large number of health-related behaviors, and examining individual differences in self-determined motivation as a moderator of the effects of autonomous and controlling motivation on health behavior. Participants were undergraduate students (N = 140) who completed measures of autonomous and controlled motivational regulations and behavioral intention for 20 health-related behaviors at an initial occasion with follow-up behavioral measures taken four weeks later. Path analysis was used to test a process model for each behavior in which motivational regulations predicted behavior mediated by intentions. Some minor idiosyncratic findings aside, between-participants analyses revealed significant effects for autonomous motivational regulations on intentions and behavior across the 20 behaviors. Effects for controlled motivation on intentions and behavior were relatively modest by comparison. Intentions mediated the effect of autonomous motivation on behavior. Within-participants analyses were used to segregate the sample into individuals who based their intentions on autonomous motivation (autonomy-oriented) and controlled motivation (control-oriented). Replicating the between-participants path analyses for the process model in the autonomy- and control-oriented samples did not alter the relative effects of the motivational orientations on intention and behavior. Results provide evidence for consistent effects of autonomous motivation on intentions and behavior across multiple health-related behaviors with little evidence of moderation by individual differences. Findings have implications for the generalizability of proposed effects in self-determination theory and intentions as a mediator of distal motivational factors on health-related behavior.
The Effect of Retrieval Focus and Emotional Valence on the Medial Temporal Lobe Activity during Autobiographical Recollection

Laboratory-based episodic memory studies, using micro-events (pictures/words), point to a role of the amygdala (AMY), an emotion-based region, in the encoding and retrieval of emotionally valenced memories. However, autobiographical memory (AM) studies, using real-life personal events, do not conclusively support AMY's involvement in AM recollection. This could be due to differences in instructions across the AM studies - i.e., whether emotional aspects were explicitly emphasized or not. The present study investigated the effect of retrieval focus on activity in emotion (AMY) and memory (hippocampus - HC) based regions of the medial temporal lobe in 17 subjects, who remembered emotional AMs while event-related fMRI data were recorded. The retrieval focus was manipulated by instructions to focus either on emotional (Emotion condition) or on other contextual (Context condition) details of the recollected AMs. The effect of retrieval focus according to the valence of AMs was also investigated by involving an equal proportion of positive and negative AMs. There were four main findings, showing both similarities and differences in retrieving positive and negative AMs. Regarding similarities, (1) focusing on Emotion was associated with increased scores of subjective re-experience of emotion and increased activity in the left AMY, for both positive and negative AMs, compared to focusing on Context; (2) the subjective emotional ratings were also positively correlated with bilateral AMY activity for both positive and negative AMs. Regarding differences, (3) focusing on Emotion was associated with increased activity for positive but not for negative AMs in the right AMY, and with (4) opposing patterns of activity linked to the valence of AMs in the left HC - i.e., increased activity for positive and decreased activity for negative AMs. These findings shed light on the role of AMY and HC in emotional AM recollection, linked to the retrieval focus and the valence of memories.
Multiple levels of regulation of the interleukin-6 system in stroke.

BACKGROUND AND PURPOSE
Serum levels of the cytokine interleukin-6 (IL-6) rise markedly in stroke. IL-6 is a key regulator of inflammatory mechanisms that play an important part in stroke pathophysiology. The action of IL-6 is modified by its soluble receptor subunits sgp130 and sIL-6R. The purpose of this study was to investigate whether serum levels of the receptor subunits are changed after ischemic stroke and to define the role of genetic influences on IL-6 expression in acute stroke.


METHODS
In 48 patients with acute stroke and 48 age- and sex-matched control subjects, serum concentrations of IL-6, sgp130, and sIL-6R were measured by enzyme-linked immunosorbent assay. Furthermore, IL-6 promoter haplotypes comprising 4 different polymorphisms (-597G-->A, -572G-->C, -373A(n)T(n), -174G-->C) were determined by DNA sequencing and allele-specific oligonucleotide polymerase chain reaction. The effect of the common haplotypes on IL-6 gene transcription was tested by transfecting reporter fusion genes in the astrocytelike cell line U373.


RESULTS
Whereas serum concentrations of IL-6 significantly rose (P<0.001), sgp130 levels were transiently reduced after stroke (P<0.05), and sIL-6R levels remained unchanged. IL-6 levels depended on the infarct size and the haplotype of the promoter region. The common haplotype A-G-8/12-C was associated with low IL-6 levels after stroke and a reduced induction of IL-6 transcription on stimulation with an adenosine analog in vitro.


CONCLUSIONS
The data demonstrate genetic variation in the expression of IL-6 in stroke. Induction of the inflammatory response by IL-6 might be enhanced by a transient downregulation of the potential IL-6 antagonist sgp130.
Pharmacokinetics and safety of itraconazole in patients with cystic fibrosis.

OBJECTIVE
To assess the pharmacokinetics of itraconazole and hydroxy-itraconazole in patients with cystic fibrosis.


METHODS
Patients were divided into those <16 and >/=16 years of age. All received itraconazole oral solution 2.5 mg/kg twice daily for 14 days. Serial blood samples were taken for itraconazole and hydroxy-itraconazole plasma level measurements. Safety was assessed from biochemistry and haematology data and reported adverse events.


RESULTS
Seventeen patients entered the study. Steady-state concentrations were achieved after maximally 8 days of dosing. On day 14 average peak plasma concentrations were 404 +/- 268 ng/mL (<16 years, n = 5) and 779 +/- 470 ng/mL (>/=16 years, n = 11 excluding one patient concurrently receiving oral clarithromycin). A high inter-subject variability in itraconazole pharmacokinetics was seen. Intra-subject variability was low. All the younger patients and 50% of the older patients failed to achieve a plasma steady-state trough concentration of >250 ng/mL. Adverse events were reported by 53% of subjects. Most were mild or moderate in intensity and not considered related to treatment. One patient withdrew from the study because of two severe adverse events. Ten significant laboratory abnormalities were reported in seven of 16 patients with paired data. Six of these were clinically relevant.


CONCLUSION
2.5 mg/kg itraconazole oral solution twice daily in patients with cystic fibrosis achieves steady-state concentrations in maximally 8 days. The pharmacokinetics showed marked inter-subject variability. Plasma concentrations of >250 ng/mL were not reached in the paediatric cohort or in 50% of the adult cohort. The dosage regimen was safe and well tolerated.
Short-course Combivir after single-dose nevirapine reduces but does not eliminate the emergence of nevirapine resistance in women.

BACKGROUND
In the Treatment Options Preservation Study (TOPS) trial, 4 or 7 days of Combivir (CBV; zidovudine/lamivudine) with maternal single-dose nevirapine (sdNVP) significantly reduced the emergence of NVP resistance as determined by virus population genotyping. To detect NVP resistance with greater sensitivity, we analysed TOPS samples by allele-specific real-time PCR (ASP).


METHODS
In a random subset of women from each arm of the trial, plasma samples from before and 6 weeks after sdNVP were analysed using ASP at codons 103, 181, 184 and 190.


RESULTS
Samples were analysed from 27 women in the sdNVP arm and 24 each in the CBV 4-day (sdNVP/CBV4) and 7-day (sdNVP/CBV7) arms. ASP detected NVP-resistant variants in week 6 samples from 70% of women in the sdNVP arm, 29% in the sdNVP/CBV4 arm and 33% in sdNVP/CBV7 arm (P<0.01 for sdNVP/CBV4 or sdNVP/CBV7 versus sdNVP; P=1.0 for sdNVP/CBV4 versus sdNVP/CBV7). Lamivudine resistance was detected by ASP in only 1 of 51 women who received CBV.


CONCLUSIONS
Short-course CBV significantly reduced but did not eliminate the emergence of NVP resistance after sdNVP. NVP-resistant variants were detected in about one-third of women despite CBV treatment, but the duration of persistence and clinical impact of these variants in response to antiretroviral therapy is uncertain.
Load-Sensitive Routing of Long-Lived IP Flows

Internet service providers face a daunting challenge in provisioning network resources, due to the rapid growth of the Internet and wide fluctuations in the underlying traffic patterns. The ability of dynamic routing to circumvent congested links and improve application performance makes it a valuable traffic engineering tool. However, deployment of load-sensitive routing is hampered by the overheads imposed by link-state update propagation, path selection, and signaling. Under reasonable protocol and computational overheads, traditional approaches to load-sensitive routing of IP traffic are ineffective, and can introduce significant route flapping, since paths are selected based on out-of-date link-state information. Although stability is improved by performing load-sensitive routing at the flow level, flapping still occurs, because most IP flows have a short duration relative to the desired frequency of link-state updates. To address the efficiency and stability challenges of load-sensitive routing, we introduce a new hybrid approach that performs dynamic routing of long-lived flows, while forwarding short-lived flows on static preprovisioned paths. By relating the detection of long-lived flows to the timescale of link-state update messages in the routing protocol, route stability is considerably improved. Through simulation experiments using a one-week ISP packet trace, we show that our hybrid approach significantly outperforms traditional static and dynamic routing schemes, by reacting to fluctuations in network load without introducing route flapping.
Facial Shape-from-shading and Recognition Using Principal Geodesic Analysis and Robust Statistics

The aim in this paper is to use principal geodesic analysis to model the statistical variations for sets of facial needle maps. We commence by showing how to represent the distribution of surface normals using the exponential map. Shape deformations are described using principal geodesic analysis on the exponential map. Using ideas from robust statistics we show how this deformable model may be fitted to facial images in which there is significant self-shadowing. Moreover, we demonstrate that the resulting shape-from-shading algorithm can be used to recover accurate facial shape and albedo from real world images. In particular, the algorithm can effectively fill-in the facial surface when more than 30% of its area is subject to self-shadowing. To investigate the utility of the shape parameters delivered by the method, we conduct experiments with illumination insensitive face recognition. We present a novel recognition strategy in which similarity is measured in the space of the principal geodesic parameters. We also use the recovered shape information to generate illumination normalized prototype images on which recognition can be performed. Finally we show that, from a single input image, we are able to generate the basis images employed by a number of well known illumination-insensitive recognition algorithms. We also demonstrate that the principal geodesics provide an efficient parameterization of the space of harmonic basis images.
COGNITIVE THERAPY FROM THE INSIDE: ENHANCING THERAPIST SKILLS THROUGH PRACTISING WHAT WE PREACH

Experiential training and personal therapy have rich traditions in various therapies as strategies to enhance self-awareness and therapist skills. However, personal experiential work has not traditionally been part of cognitive therapy (CT) training. The purpose of the present study is to map the impact of personal experiential work on CT skills in a group of CT practitioners. Fourteen cognitive therapists undertook training courses utilizing a structured approach to self-practice of CT techniques, known as self-practice/self-reflection (SP/ SR). Six therapists from one training group engaged in ‘‘co-therapy’’ sessions with a partner, while eight therapists from another training group practised CT techniques on their own. Both groups engaged in regular written reflections about their experience. Follow-up 1–5 months after the courses identified six areas of self-reported skill enhancement: Refinement of specific CT skills; Enriched communication of the conceptual framework of CT; Increased attention to the therapeutic relationship; Empathic attunement; Therapist self-reflection; and Therapeutic flexibility. The results suggested that SP/SR enhances the ‘‘professional artistry’’ of therapists, a finding consistent with literature suggesting that reflection is a key process in the development of therapist expertise. It is concluded that SP/SR represents a promising training strategy for cognitive therapists.