Psychological targeting as an effective approach to digital mass persuasion.

People are exposed to persuasive communication across many different contexts: Governments, companies, and political parties use persuasive appeals to encourage people to eat healthier, purchase a particular product, or vote for a specific candidate. Laboratory studies show that such persuasive appeals are more effective in influencing behavior when they are tailored to individuals' unique psychological characteristics. However, the investigation of large-scale psychological persuasion in the real world has been hindered by the questionnaire-based nature of psychological assessment. Recent research, however, shows that people's psychological characteristics can be accurately predicted from their digital footprints, such as their Facebook Likes or Tweets. Capitalizing on this form of psychological assessment from digital footprints, we test the effects of psychological persuasion on people's actual behavior in an ecologically valid setting. In three field experiments that reached over 3.5 million individuals with psychologically tailored advertising, we find that matching the content of persuasive appeals to individuals' psychological characteristics significantly altered their behavior as measured by clicks and purchases. Persuasive appeals that were matched to people's extraversion or openness-to-experience level resulted in up to 40% more clicks and up to 50% more purchases than their mismatching or unpersonalized counterparts. Our findings suggest that the application of psychological targeting makes it possible to influence the behavior of large groups of people by tailoring persuasive appeals to the psychological needs of the target audiences. We discuss both the potential benefits of this method for helping individuals make better decisions and the potential pitfalls related to manipulation and privacy.

Usability of daily SF36 questionnaires to capture the QALD variation experienced after vaccination with AS03A-adjuvanted monovalent influenza A (H5N1) vaccine in a safety and tolerability study.

BACKGROUND: This study aims to describe the short-term reactogenicity of the AS03-adjuvanted H5N1 vaccine expressed through adverse events (AEs) and quality-adjusted life-day (QALD) scores. The AEs are likely to be short-term and therefore the quality of life (QoL) questionnaire, SF-36v2, was administered daily to record changes over seven days. A more sensitive application of this instrument should allow for a better understanding of short-term tolerability of adjuvanted vaccines. METHODS: Participants (N = 50) received a 2-dose vaccination schedule. Solicited (collected daily: days 0 to 7 [post dose 1] and 21 to 28 [post dose 2]) and unsolicited (collected weekly until day 21) AEs were collected via diary cards. The QoL questionnaires were completed daily (days 0-6) and weekly (days 0, 6, 21, 27) after dose one. Questionnaire data were transformed into SF-6D scores to report QALDs. It was hypothesized post-hoc that the QALD and daily AEs scores should correlate if discrete QoL-changes were captured. RESULTS: Pain (92%) and muscle ache (66%) were the most commonly reported solicited local and general AEs respectively, neither increased in intensity nor in frequency after dose 2. No safety concerns were identified during the study. A correlation between the daily AEs and QALD scores existed (correlation coefficient, - 0.97 (p < 0.001)). The impact of the AEs scores on the QALD was marginal (- 0.02 max for one day). CONCLUSION: Similarly with other H5N1 studies, no safety concern was identified throughout the study. Some time-limited variations in QALD-scores were reported. Our results imply that daily administration of the SF-36v2 captures changes in QALD-scores. TRIAL REGISTRATION: ClinicalTrials.gov . NCT01788228. Registered 11 February 2013.

The French-Canadian validation of a disease-specific, patient-reported outcome measure for lupus.

OBJECTIVES: The objective of this paper is to perform the cross-cultural validation of the French version of the LupusPRO, a disease-targeted patient-reported outcome measure, among systemic lupus erythematosus (SLE) patients in Canada. METHODS: The French version of the LupusPRO and the MOS SF-36 were administered; demographic, clinical and serological characteristics were obtained. Disease activity (SELENA-SLEDAI and the Lupus Foundation of America definition of flare) and damage (SLICC/ACR SDI) were assessed. Physician disease activity and damage assessments were ascertained using visual analog scales. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent and discriminant validity (against corresponding domains of the SF-36), criterion validity (against disease activity, damage or health status) and known group validity were tested. RESULTS: A total of 99 French-Canadian SLE patients participated (97% women, mean (SD) age 45.2 (14.5) years). The median (IQR) SELENA-SLEDAI and SDI were 3.5 (6.0) and 1.0 (2.0), respectively. The ICR of the LupusPRO domains ranged from 0.81 to 0.93 (except for lupus symptoms, procreation and coping), while TRT ranged from 0.72 to 0.95. Convergent and discriminant validity, criterion validity and known group validity against disease activity, damage and health status measures were observed. Confirmatory factor analysis showed a good fit. CONCLUSION: The LupusPRO has fair psychometric properties among French-Canadian patients with SLE.

Qualitative validation of the FACIT-fatigue scale in systemic lupus erythematosus.

OBJECTIVE: Fatigue in systemic lupus erythematosus (SLE) is burdensome and must be assessed using validated scales. Although the psychometric properties of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale in SLE have been evaluated previously, its content validity in this disease remains to be evaluated. The study objective was, therefore, to evaluate content validity of the FACIT-Fatigue in SLE. METHODS: Three SLE focus groups (n=21) in the United States were conducted using semi-structured interviews. Participant comments were categorized by response type, and relative response strength was qualitatively assessed. RESULTS: Participants were mostly female (90%; n=19), white (57%; n=12) with a mean age of 43.7 years (range=28-70). Most scale items were considered relevant with the exception of four items for which participant interpretations varied. Consistent with the scale's measurement model, "listless" on item 3 ("I feel listless ('washed out')") was interpreted as physical or mental impairment. Participant responses to item 8 ("I am able to do my usual activities") sometimes included influence of other health conditions, which is acceptable because it is difficult to separate disease-specific and general fatigue. Some participants found item 7 ("I have energy") irrelevant and most could not relate to item 10 ("I am too tired to eat"). However, both items were intended to capture the extreme ends of fatigue (item 7, ceiling; item 10, floor). CONCLUSIONS: From a content perspective, items of the FACIT-Fatigue scale were relevant for measuring fatigue in SLE.

Cross-cultural validation of a disease-specific patient-reported outcome measure for lupus in Philippines.

OBJECTIVE: LupusPRO is a disease-targeted patient-reported outcome measure that was developed and validated among US patients with systemic lupus erythematosus (SLE). We report the cross-cultural validation results of the LupusPRO English-language version among Filipino SLE patients. METHOD: The 43-item LupusPRO was pretested in 15 SLE individuals, then administered to 106 SLE patients, along with short-form SF36 and the EQ5D visual analogue scale. A mail/drop-back LupusPRO and change in health status item survey were returned within two to three days. Demographics, clinical and serological characteristics, disease activity and damage measured by PGA, SELENA-SLEDAI, LFA Flare, and SLICC-ACR SLE damage index (SDI) were collected. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent validity (corresponding SF36 domains) and criterion validity (against general health and disease activity measures) were tested. Reported p values are two tailed. RESULTS: A total of 121 Filipino SLE subjects (95% women, median age 31.0 ± 16 years) with at least a high school level of English instruction participated. Median (IQR) PGA, SLEDAI and SDI were 0.0 (1.0), 2.0 (10) and 0 (1), respectively. ICR exceeded 0.7 for all domains except the lupus symptoms domain. TRT was greater than 0.85 for all LupusPRO domains. Convergent and criterion validity were observed against corresponding SF36 domains and disease activity measures. The tool was well received by patients. Confirmatory factor analysis showed good fit. CONCLUSION: English LupusPRO has fair psychometric properties among SLE patients in the Philippines, and is now available for inclusion in clinical trials and longitudinal studies to test responsiveness to change.

Spanish LupusPRO: cross-cultural validation study for lupus.

PURPOSE: LupusPRO is a disease-targeted, patient-reported, outcome measure that was developed and validated among US patients with systemic lupus erythematosus (SLE). To expand the availability and use of the tool, we undertook a cross-cultural adaptation and validation study of the Spanish-translated version of the LupusPRO. METHOD: Forward and back translations of the 43-item English LupusPRO were undertaken and pretested in five individuals. The finalized Spanish version was administered to 211 SLE patients of Hispanic ancestry from the US and Latin America. Short Form-36 (Spanish) and Spanish LupusPRO were also administered. Disease activity was ascertained using the systemic lupus erythematosus disease activity index. A Spanish LupusPRO questionnaire that could be completed within 2-3 days was mailed to SLE patients of Hispanic ancestry and they mailed it back. Internal consistency reliability, test-retest reliability, criterion validity (against disease activity or health status) and convergent validity were tested. All reported p values are two-tailed. RESULTS: A total of 211 Spanish-speaking SLE patients (90% women) participated. Test-retest reliability of LupusPRO domains ranged from 0.80-0.95, while internal consistency reliability of the domains ranged from 0.71-0.96. Convergent validity with corresponding domains of the SF-36 was present. All health-related quality of life domains of the LupusPRO (except procreation) performed well against disease activity measures, establishing its criterion validity. Confirmatory factor analysis showed a good fit. CONCLUSION: The Spanish LupusPRO has fair psychometric properties and is now available to be included in clinical trials and in longitudinal studies for testing of responsiveness to change.

68Ga-NODAGA-RGDyK for αvß3 integrin PET imaging. Preclinical investigation and dosimetry.

AIM: To visualize neovasculature and/or tumour integrin αvß3 we selected the binding moiety Arg-Gly-Asp-D-Tyr-Lys (RGDyK) coupled to NODAGA for labeling with 68Ga. METHODS: NODAGA-RGDyK (ABX) was labeled with the 68Ga eluate from the 68Ge generator IGG100 using the processor unit PharmTracer. Biodistribution was measured in female Hsd mice sacrificed 10, 30, 60 and 90 min after i.v. injection of 68Ga-NODAGA-RGDyK for OLINDA dosimetry extrapolated to humans. Tumour targeting was studied in SCID mice bearing A431 and other tumour transplants using microPET and biodistribution measurements. RESULTS: Effective half-life of 68Ga-NODAGA-RGDyK was ~25 min for total body and most organs except liver and spleen that showed stable activity retention. With a bladder voiding interval of 0.5 h the calculated effective dose (ED) was 0.012 and 0.016 mSv/MBq for males and females, respectively. Rapid uptake within 10 min was observed in A431 tumours with dynamic PET followed by a slow release. Biodistribution measurements showed a 68Ga-NODAGA-RGDyK uptake in A431 tumours of 3.4±0.4 and 2.7±0.3%ID/g at 1 and 2 h, respectively. Similar uptakes were observed in a mouse and human breast and ovarian cancer xenografts. Co-injection of excess (5 mg/kg) unlabeled NODAGA-RGDyK with the radiotracer reduced tumour uptake at one hour to 0.23±0.01%ID/g, but similarly decreased uptake in normal organs as well. When unlabeled peptide was injected 15 min after 68Ga-NODAGA-RGDyK, uptake diminished particularly in tumour and adrenals, suggestive of a different binding mode compared with other normal tissues. CONCLUSION: NODAGA-RGDyK was reliably labeled with 68Ga and revealed a predicted ED of 0.014 mSv/MBq. Tumour uptake was rapid and significant and was chased with unlabeled RGDyK in a similar manner as adrenal uptake.

A sperm cytoskeletal protein that signals oocyte meiotic maturation and ovulation.

Caenorhabditis elegans oocytes, like those of most animals, arrest during meiotic prophase. Sperm promote the resumption of meiosis (maturation) and contraction of smooth muscle-like gonadal sheath cells, which are required for ovulation. We show that the major sperm cytoskeletal protein (MSP) is a bipartite signal for oocyte maturation and sheath contraction. MSP also functions in sperm locomotion, playing a role analogous to actin. Thus, during evolution, MSP has acquired extracellular signaling and intracellular cytoskeletal functions for reproduction. Proteins with MSP-like domains are found in plants, fungi, and other animals, suggesting that related signaling functions may exist in other phyla.

Fluorodeoxyuridine mediated cell cycle synchronization in S-phase increases the Auger radiation cell killing with 125I-iododeoxyuridine.

AIM: 125I-iododeoxyuridine is a potential Auger radiation therapy agent. Its incorporation in DNA of proliferating cells is enhanced by fluorodeoxyuridine. Here, we evaluated therapeutic activities of 125I-iododeoxyuridine in an optimized fluorodeoxyuridine pre-treatment inducing S-phase synchronization. METHODS: After S-phase synchronization by fluorodeoxyuridine, cells were treated with 125I-iododeoxyuridine. Apoptosis analysis and S-phase synchronization were studied by flow cytometry. Cell survival was determined by colony-forming assay. Based on measured growth parameters, the number of decays per cell that induced killing was extrapolated. RESULTS: Treatment experiments showed that 72 to 91% of synchronized cells were killed after 0.8 and 8 kBq/ml 125I-iododeoxyuridine incubation, respectively. In controls, only 8 to 38% of cells were killed by corresponding 125I-iododeoxyuridine activities alone and even increasing the activity to 80 kBq/ml gave only 42 % killing. Duplicated treatment cycles or repeated fluorodeoxyuridine pre-treatment allowed enhancing cell killing to >95 % at 8 kBq/ml 125I-iododeoxyuridine. About 50 and 160 decays per S-phase cells in controls and S-phase synchronization, respectively, were responsible for the observed cell killing at 0.8 kBq/ml radio-iododeoxyuridine. CONCLUSION: These data show the successful application of fluorodeoxyuridine that provided increased 125I-iododeoxyuridine Auger radiation cell killing efficacy through S-phase synchronization and high DNA incorporation of radio-iododeoxyuridine.

GARDASIL: prophylactic human papillomavirus vaccine development--from bench top to bed-side.

GARDASIL (Merck, Whitehouse Station, NJ) is a non-infectious recombinant, quadrivalent vaccine prepared from the highly purified virus-like particles (VLPs) of the major capsid proteins of human papillomavirus (HPV) types 6, 11, 16, and 18. GARDASIL is the first vaccine approved for use in women aged 9-26 years for the prevention of cervical cancer and genital warts, as well as vulvar and vaginal precancerous lesions. This report describes some of the key preclinical efforts, achievements in pharmaceutical development, in vivo animal evaluation, and clinical trial data.

Endovascular isolated hepatic perfusion under pneumoperitoneum.

AIMS: Isolated hepatic perfusion (IHP) allows loco-regional administration of high drug doses for cancer treatment. Minimally invasive endovascular occlusion techniques can be used for IHP, but control of leakage remains a major drawback. We hypothesized that the increased intraabdominal pressure generated by a CO(2)-pneumoperitoneum (PP) can reduce the leakage rate of hypoxic endovascular IHP by mechanical compression of the capillary beds connecting the liver to the systemic circulation. METHODS: IHP was performed on adult pigs through laparotomy using a fenestrated double balloon-catheter placed into the retrohepatic vena cava to collect the hepatic outflow which was reinfused into the hepatic artery through an extracorporeal circulation system. Each pig underwent IHP during four consecutive phases: abdomen open (Phase I), abdomen closed under a 15 and 20 mmHg pneumoperitoneum (Phase II and III, respectively) and abdomen re-opened (Phase IV). The leakage rate from the liver to the systemic circulation was continuously monitored using a nuclear medicine technique. The systemic arterial pressure, the IHP inflow and outflow pressures and the flow rate were recorded. RESULTS: Leakage from the hepatic extracorporeal circulation to the systemic circulation occurred in all animals during Phase I. Under PP (Phases II and III), two leakage profiles were observed: (1) a major increase of the leakage rate in two animals with a high differential pressure (>50 mmHg) between the IHP inflow and the systemic pressures; (2) no change or a decrease of the leakage rate in the other three animals who had a low or negative differential pressure (<30 mmHg). Leakage was undetectable in all animals after exsufflation of the PP (Phase IV). CONCLUSIONS: IHP under PP is feasible. Leakage is not reduced during PP. A high gradient between the IHP inflow and the systemic pressure increases systemic leakage during PP. Upon release of the PP, the leakage is most likely redirected towards the volume depleted low resistance portal territory.

A Caenorhabditis elegans wee1 homolog is expressed in a temporally and spatially restricted pattern during embryonic development.

A wee1 homolog, wee-1.1, is expressed in both a temporally and spatially restricted pattern during early Caenorhabditis elegans embryogenesis, and is undetectable throughout the remainder of embryogenesis. The wee-1.1 message appears to be zygotically expressed in the somatic founder cell E of the 12-cell embryo. This expression disappears when the E blastomere divides for the first time. The wee-1.1 message then appears transiently in the nuclei of the eight great-granddaughter cells of the AB somatic founder cell, just before these cells divide in the 16-cell embryo. Following this division, the wee-1.1 mRNA is no longer detectable throughout the remainder of embryogenesis. The expression of wee-1.1 in the E blastomere and in the AB progeny appears to be restricted to nuclei in prophase and metaphase of the cell cycle. Analysis of the wee-1.1 mRNA expression pattern in maternal-effect lethal mutants suggests that this expression pattern is restricted to cells of the E and AB fates in the early embryo. This mRNA expression pattern is restricted to a 10-15-min span of embryonic development and may be regulating the timing of crucial cell divisions at this early stage of development.

The four cdc25 genes from the nematode Caenorhabditis elegans.

During eukaryotic evolution, multicellular organisms have evolved multiple members of gene families that may display unique, partially overlapping, or redundant functions during development. More than 75% of the C. elegans genome has been sequenced, which represents approximately 95% of the coding sequences. This provides a unique opportunity to identify most, if not all, of the members of a given gene family. We have searched the C. elegans genome database for members of a key family of cell cycle regulators, the CDC25 phosphatases, and have identified four genes. The four C. elegans genes represent a larger family within a single organism than has been reported so far in Drosophila, mice and humans. An amino acid comparison revealed a high degree of similarity and identity within the phosphatase domain. This analysis also identified an expanded consensus sequence that can be used to discover new members of the CDC25 phosphatase family. However, the four C. elegans sequences display a few novel amino acid substitutions in the residues surrounding the invariant catalytic motif CX5R. These data demonstrate the value of genome database searching for identifying new members of known gene families, understanding genetic diversity, and for studying gene structure.

Psychometric and clinical tests of validity of the Japanese SF-36 Health Survey.

Cross-sectional data from a representative sample of the general population in Japan were analyzed to test the validity of Japanese SF-36 Health Survey scales as measures of physical and mental health. Results from psychometric and clinical tests of validity were compared. Principal components analyses were used to test for the hypothesized physical and mental dimensions of health and the pattern of scale correlations with those components. To test the clinical validity of SF-36 scale scores, self-reports of chronic medical conditions and the Zung Self-Rating Depression Scale were used to create mutually exclusive groups differing in the severity of physical and mental conditions. The pattern of correlations between the SF-36 scales and the two empirically derived components generally confirmed hypotheses for most scales. Results of psychometric and clinical tests of validity were in agreement for the Physical Functioning, Role-Physical, Vitality, Social Functioning, and Mental Health scales. Relatively less agreement between psychometric and clinical tests of validity was observed for the Bodily Pain, General Health, and Role-Emotional scales, and the physical and mental health factor content of those scales was not consistent with hypotheses. In clinical tests of validity, the General Health, Bodily Pain, and Physical Functioning scales were the most valid scales in discriminating between groups with and without a severe physical condition. Scales that correlated highest with mental health in the components analysis (Mental Health and Vitality) also were most valid in discriminating between groups with and without depression. The results of this study provide preliminary interpretation guidelines for all SF-36 scales, although caution is recommended in the interpretation of the Role-Emotional, Bodily Pain, and General Health scales pending further studies in Japan.

The factor structure of the SF-36 Health Survey in 10 countries: results from the IQOLA Project. International Quality of Life Assessment.

Studies of the factor structure of the SF-36 Health Survey are an important step in its construct validation. Its structure is also the psychometric basis for scoring physical and mental health summary scales, which are proving useful in simplifying and interpreting statistical analyses. To test the generalizability of the SF-36 factor structure, product-moment correlations among the eight SF-36 Health Survey scales were estimated for representative samples of general populations in each of 10 countries. Matrices were independently factor analyzed using identical methods to test for hypothesized physical and mental health components, and results were compared with those published for the United States. Following simple orthogonal rotation of two principal components, they were easily interpreted as dimensions of physical and mental health in all countries. These components accounted for 76% to 85% of the reliable variance in scale scores across nine European countries, in comparison with 82% in the United States. Similar patterns of correlations between the eight scales and the components were observed across all countries and across age and gender subgroups within each country. Correlations with the physical component were highest (0.64 to 0.86) for the Physical Functioning, Role Physical, and Bodily Pain scales, whereas the Mental Health, Role Emotional, and Social Functioning scales correlated highest (0.62 to 0.91) with the mental component. Secondary correlations for both clusters of scales were much lower. Scales measuring General Health and Vitality correlated moderately with both physical and mental health components. These results support the construct validity of the SF-36 translations and the scoring of physical and mental health components in all countries studied.

The equivalence of SF-36 summary health scores estimated using standard and country-specific algorithms in 10 countries: results from the IQOLA Project. International Quality of Life Assessment.

Data from general population surveys (n = 1771 to 9151) in nine European countries (Denmark, France, Germany, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom) were analyzed to test the algorithms used to score physical and mental component summary measures (PCS-36/MCS-36) based on the SF-36 Health Survey. Scoring coefficients for principal components were estimated independently in each country using identical methods of factor extraction and orthogonal rotation. PCS-36 and MCS-36 scores were also estimated using standard (U.S.-derived) scoring algorithms, and results were compared. Product-moment correlations between scores estimated from standard and country-specific scoring coefficients were very high (0.98 to 1.00) for both physical and mental health components in all countries. As hypothesized for orthogonal components, correlations between physical and mental components within each country were very low (0.00 to 0.12) for both estimation methods. Mean scores for PCS-36 differed by as much as 3.0 points across countries using standard scoring, and mean scores for MCS-36 differed across countries by as much as 6.4 points. In view of the high degree of equivalence observed within each country, using standard and country-specific algorithms, we recommend use of standard scoring algorithms for purposes of multinational studies involving these 10 countries.

Structural characteristics of an abnormal protein influencing its proteolytic susceptibility.

Structural properties of two similar beta-galactosidase fragments were investigated to determine how they influence the fragments' degradation rate in Escherichia coli. Both fragments resulting from a C-terminal nonsense mutation in lacZ, the CSH11 polypeptide and its 90 kDa degradative intermediate, exist predominantly as monomer subunits instead of in the tetrameric form characteristic of the native enzyme. However, both fragments appear to produce trace amounts of dimers and tetramers. The tetramer and higher molecular weight aggregates formed by the wild-type subunit confer greater protection for the enzyme's N-terminal auto-alpha polypeptide than does the monomer state of the beta-galactosidase fragments. The thermally induced aggregation of both beta-galactosidase fragments correlates with their sensitivity to alpha-chymotrypsin. The relatively low thermal stability of the 90 kDa degradative intermediate appears to be the cause of the significant increase in its proteolytic susceptibility at moderately high temperatures.