Institutionalizing Innovation: From Pilot to Scale for Co-Packaged Oral Rehydration Salts and Zinc-A Case Study in Zambia.

We document the development and institutionalization in Zambia of a health innovation for diarrhea treatment aimed at children aged younger than 5 years: a unique oral rehydration salts and zinc (ORSZ) co-pack. Seven recommendations from the World Health Organization/ExpandNet are used retrospectively to analyze and describe the successful scale-up of this innovation from its concept stage, including in-country expansion and policy, institutional, and regulatory changes. The 7 recommendations comprise using a participatory process, tailoring to the country context, designing research to test the innovation, testing the innovation, identifying success factors, and scaling up. The scale-up of co-packaged ORSZ in Zambia is shown to be sustainable. Five years after donor funding ended in 2018, an independent, local manufacturer continues to supply the private and public sectors on a commercially viable basis. Furthermore, national coverage of ORSZ increased from less than 1% in 2012 to 34% in 2018. A key success factor was the continuous facilitation over 8 years (spanning planning, trial, evaluation, and scale-up) by a learning and steering group chaired by the Ministry of Health, open to all and focused on learning transfer and ongoing alignment with other initiatives. Other success factors included a long lead-in of inclusive initial consultation, ideation, and planning with all key stakeholders to build on and mobilize existing resources, knowledge, structures, and systems; alignment with government policy; thorough testing and radical review of the product and its value chain before scale-up, including manufacture, distribution, policy, and regulatory matters; and adoption by the government of a co-packaging strategy to ensure cases of childhood diarrhea are treated with ORSZ. With appropriate local adaptations, this approach to scale-up could be replicated in other low- and middle-income countries as a strategy to increase coverage of ORSZ and potentially other health products.

Age of Diagnosis, Fidelity and Acceptability of an Early Diagnosis Clinic for Cerebral Palsy: A Single Site Implementation Study.

Cerebral palsy (CP) diagnosis is historically late, at between 12 and 24 months. We aimed to determine diagnosis age, fidelity to recommended tests and acceptability to parents and referrers of an early diagnosis clinic to implement a recent evidence-based clinical guideline for the early diagnosis of CP. A prospective observational case series of infants <12 months with detectable risks for CP attending our clinic was completed with data analysed cross-sectionally. Infants had a high risk of CP diagnosis at a mean age of 4.4 (standard deviation [SD] 2.3) months and CP diagnosis at 8.5 [4.1] months. Of the 109 infants seen, 57% had a diagnosis of CP or high risk of CP, showing high specificity to our inclusion criteria. Parent and referrer acceptability of the clinic was high. Paediatricians had the highest rate of referral (39%) followed by allied health (31%), primary carer (14%) and other health workers (16%). Fidelity to the guideline was also high. All infants referred <5 mths had the General Movements Assessment (GMA) and all except one had the Hammersmith Infant Neurological Examination (HINE) administered. N = 92 (84%) of infants seen had neuroimaging, including n = 53 (49%) who had magnetic resonance imaging (MRI), showing recommended tests are feasible. Referral to CP-specific interventions was at 4.7 [3.0] months, sometimes before referral to clinic. Clinicians can be confident CP can be diagnosed well under 12 months using recommended tools. This clinic model is acceptable to parents and referrers and supports access to CP-specific early interventions when they are likely to be most effective.

Evidence for Age-Equivalent and Task-Dissociative Metacognition in the Memory Domain.

Research suggests that metacognitive monitoring ability does not decline with age. For example, judgments-of-learning (JOL) accuracy is roughly equivalent between younger and older adults. But few studies have asked whether younger and older adults' metacognitive ability varies across different types of memory processes (e.g., for items vs. pairs). The current study tested the relationship between memory and post-decision confidence ratings at the trial level on item (individual words) and associative (word pairs) memory recognition tests. As predicted, younger and older adults had similar metacognitive efficiency, when using meta-d'/d', a measure derived from Signal Detection Theory, despite a significant age effect favoring younger adults on memory performance. This result is consistent with previous work showing age-equivalent metacognitive efficiency in the memory domain. We also found that metacognitive efficiency was higher for associative memory than for item memory across age groups, even though associative and item recognition memory (d') were statistically equivalent. Higher accuracy on post-test decision confidence ratings for associative recognition relative to item recognition on resolution accuracy itself (meta-d') and when corrected for performance differences (meta-d'/d') are novel findings. Implications for associative metacognition are discussed.

Evidence for an Age-Related Positivity Effect in Metacognitive Judgments.

OBJECTIVES: If older adults (OAs) are focused on emotionally meaningful goals in late life, they should demonstrate memory biases for positive stimuli over neutral and negative stimuli and, arguably, these cognitive biases should be reflected in their metacognitive judgments of learning (JOLs). To address this question, we examined age differences in metacognitive monitoring of emotionally valenced stimuli. METHOD: Younger adults (YAs) and OAs (N = 85) studied positive, neutral, and negative words and made immediate JOLs, followed by a 2-alternative forced choice (2AFC) recognition memory task. RESULTS: Analyses of JOLs revealed evidence for a positivity effect in metacognitive judgments for OAs and an emotional salience effect in YAs. YAs recognized more words than OAs, but valence did not affect number of words recognized and did not moderate age differences in memory (p = .055). Memory monitoring as measured by resolution accuracy was equivalent in YAs and OAs. Positive affect was higher and negative affect was lower in OAs relative to YAs, lending additional evidence to the emergence of a positive orientation in older adulthood. DISCUSSION: These results provide intriguing and novel support for the positivity effect in the domain of metacognitive aging, adding to what is known in memory, attention, and emotion domains. Our findings fall squarely within socioemotional and metacognitive theoretical frameworks from which they were derived. We discuss research directions that might identify mechanisms by which affective states and stimuli interact to produce metacognitive outcomes in late life.

Correction: Artificial neural networks reveal individual differences in metacognitive monitoring of memory.

[This corrects the article DOI: 10.1371/journal.pone.0220526.].

Artificial neural networks reveal individual differences in metacognitive monitoring of memory.

Previous work supports an age-specific impairment for recognition memory of pairs of words and other stimuli. The present study tested the generalization of an associative deficit across word, name, and nonword stimulus types in younger and older adults. Participants completed associative and item memory tests in one of three stimulus conditions and made metacognitive ratings of perceptions of self-efficacy, task success ("postdictions"), strategy success, task effort, difficulty, fatigue, and stamina. Surprisingly, no support was found for an age-related associative deficit on any of the stimulus types. We analyzed our data further using a multilayer perceptron artificial neural network. The network was trained to classify individuals as younger or older and its hidden unit activities were examined to identify data patterns that distinguished younger from older participants. Analysis of hidden unit activities revealed that the network was able to correctly classify by identifying three different clusters of participants, with two qualitatively different groups of older individuals. One cluster of older individuals found the tasks to be relatively easy, they believed they had performed well, and their beliefs were accurate. The other cluster of older individuals found the tasks to be difficult, believed they were performing relatively poorly, yet their beliefs did not map accurately onto their performance. Crucially, data from the associative task were more useful for neural networks to discriminate between younger and older adults than data from the item task. This work underscores the importance of considering both individual and age differences as well as metacognitive responses in the context of associative memory paradigms.

The role of encoding strategy in younger and older adult associative recognition: A think-aloud analysis.

Older adults have especially poor recognition memory for word pairs, and research suggests this associative deficit manifests primarily in older adults' higher rates of false alarms. This could result from older adults either failing to generate meaningful (deep) mediators at study, or failing to benefit from having generated deep mediators at test. Younger and older adults performed a recognition memory task for words and word pairs. A think-aloud analysis of their spontaneous encoding strategies (repetition, shallow mediators, deep mediators) revealed that generation of deep mediators did not differ between younger and older adults, and was associated with high hit rates for items and associates in both age groups. However, generation of deep mediators was inversely related to false alarm rates in younger adults but not older adults. A trial-level analysis of encoding strategies and recognition responses revealed that younger adults benefited from having generated deep mediators when presented with corresponding recombined pairs at test as shown in their lower false alarm rates. In contrast, older adults who generated deep mediators during study (e.g., to blanket-figure) did not benefit from having done so when they encountered the corresponding recombined pairs at test (blanket-summer and district-figure). Their false alarm rates to pairs at test were unrelated to generation of deep mediators at study. These results suggest that many older adults have difficulty retrieving their mediators when presented with recombined pairs at test, or their mediators are not distinct enough to distinguish intact pairs from recombined pairs at test, or some combination of both. (PsycINFO Database Record

Perceptions of competence: age moderates views of healthy aging and Alzheimer's disease.

UNLABELLED: BACKGROUND/STUDY CONTEXT: Older adults have more complex and differentiated views of aging than do younger adults, but less is known about age-related perceptions of Alzheimer's disease. This study investigated age-related perceptions of competence of an older adult labeled as "in good health" (healthy) or "has Alzheimer's disease" (AD), using a person-perception paradigm. It was predicted that older adults would provide more differentiated assessments of the two targets than would younger adults. METHODS: Younger (n=86; 18-36 years) and older (n=66; 61-95 years) adults rated activities of daily living (ADL), instrumental activities of daily living (IADL), and memory abilities of a female target aged 75 years, described as healthy or with AD. Data on anxiety about aging, knowledge of and experience with aging and AD, knowledge of memory aging, and positive and negative biases toward aging and AD were also collected. RESULTS: Older adults perceived the healthy target as more capable of cognitively effortful activities (e.g., managing finances) and as possessing better memory abilities than the AD target. As predicted, these differences were greater than differences between targets perceived by younger adults. The interaction effect remained significant after statistically controlling for relevant variables, including education and gender. Additionally, exploratory analyses revealed that older adults held less positively biased views of AD than younger adults, but negatively biased views were equivalent between age groups. CONCLUSION: The results demonstrate that mere labels of "healthy" and "Alzheimer's disease" produce significant and subtle age differences in perceived competencies of older adults, and that biases towards AD vary by age group and valence. Our findings extend the person-perception paradigm to an integrative analysis of aging and AD, are consistent with models of adult development, and complement current research and theory on stereotypes of aging. Future directions for research on perceptions of aging are suggested.

Are vocabulary tests measurement invariant between age groups? An item response analysis of three popular tests.

Relatively high vocabulary scores of older adults are generally interpreted as evidence that older adults possess more of a common ability than younger adults. Yet, this interpretation rests on empirical assumptions about the uniformity of item-response functions between groups. In this article, we test item response models of differential responding against datasets containing younger-, middle-aged-, and older-adult responses to three popular vocabulary tests (the Shipley, Ekstrom, and WAIS-R) to determine whether members of different age groups who achieve the same scores have the same probability of responding in the same categories (e.g., correct vs. incorrect) under the same conditions. Contrary to the null hypothesis of measurement invariance, datasets for all three tests exhibit substantial differential responding. Members of different age groups who achieve the same overall scores exhibit differing response probabilities in relation to the same items (differential item functioning) and appear to approach the tests in qualitatively different ways that generalize across items. Specifically, younger adults are more likely than older adults to leave items unanswered for partial credit on the Ekstrom, and to produce 2-point definitions on the WAIS-R. Yet, older adults score higher than younger adults, consistent with most reports of vocabulary outcomes in the cognitive aging literature. In light of these findings, the most generalizable conclusion to be drawn from the cognitive aging literature on vocabulary tests is simply that older adults tend to score higher than younger adults, and not that older adults possess more of a common ability.

Metacognitive awareness of the associative deficit for words and names.

Older adults have considerable impairment in associative recognition despite minimal age differences in item recognition. The magnitude of this associative deficit varies by type of stimuli, strategy utilization, and other mediators and moderators ( Old & Naveh-Benjamin, 2008 , Psychology and Aging, 23, 104-118). Name pair stimuli have not been used to test the associative deficit hypothesis (ADH), although tests using name-face stimuli support the ADH. Additionally, metacognitive awareness of the ADH has not been investigated. We tested the ADH with word and name pair stimuli, and predicted that age-related associative deficits would be larger for words than names because names, unlike most common nouns, lack certain semantic properties that could be used to bind pairs of names together. Results supported the ADH for words but not names: Younger and older adults recognized equivalently fewer names on the associative test relative to the item test. As predicted, self-efficacy was higher for younger than older adults. Surprisingly, self-efficacy for the associative test was higher than for the item test but post-test estimates of performance success (postdictions) were higher for the item test than for the associative test, suggesting sensitivity by participants to different task demands in the item and associative tests following recognition attempts. Metacognitive accuracy was better for words than names and for the item test than associative test, and equivalent between age groups. Overall, participants overestimated their name recognition abilities. Our findings extend support for the ADH to a conceptually important and ecologically valid domain (names) and provide new data on metacognitive aspects of the ADH.

Psychometric properties of scores on three Black racial identity scales.

In this study, we examined the internal consistency and the structural validity of scores on the African Self-Consciousness Scale (ASCS), the Multidimensional Inventory of Black Identity (MIBI), and the Cross Racial Identity Scale (CRIS). Participants consisted of 225 African American college students--75 attending predominantly White institutions (PWIs) and 150 attending historically Black colleges and universities (HBCUs). Internal consistency estimates were above .60 for scores on one ASCS subscale, six MIBI subscales, and six CRIS subscales. Exploratory factor analytic procedures supported a two-factor structure for ASCS scores, a five-factor structure for MIBI scores, and a six-factor structure for CRIS scores. Implications for Black racial identity and scale development are discussed.

Quinols as novel therapeutic agents. 2.(1) 4-(1-Arylsulfonylindol-2-yl)-4-hydroxycyclohexa-2,5-dien-1-ones and related agents as potent and selective antitumor agents.

A series of substituted 4-(1-arylsulfonylindol-2-yl)-4-hydroxycyclohexa-2,5-dien-1-ones (indolylquinols) has been synthesized on the basis of the discovery of lead compound 1a and screened for antitumor activity. Synthesis of this novel series was accomplished via the "one-pot" addition of lithiated (arylsulfonyl)indoles to 4,4-dimethoxycyclohexa-2,5-dienone followed by deprotection under acidic conditions. Similar methodology gave rise to the related naphtho-, 1H-indole-, and benzimidazole-substituted quinols. A number of compounds in this new series were found to possess in vitro human tumor cell line activity substantially more potent than the recently reported antitumor 4-substituted 4-hydroxycyclohexa-2,5-dien-1-ones(1) with similar patterns of selectivity against colon, renal, and breast cell lines. The most potent compound in the series in vitro, 4-(1-benzenesulfonyl-6-fluoro-1H-indol-2-yl)-4-hydroxycyclohexa-2,5-dienone (1h), exhibits a mean GI(50) value of 16 nM and a mean LC(50) value of 2.24 muM in the NCI 60-cell-line screen, with LC(50) activity in the HCT 116 human colon cancer cell line below 10 nM. The crystal structure of the unsubstituted indolylquinol 1a exhibits two independent molecules, both participating in intermolecular hydrogen bonds from quinol OH to carbonyl O, but one OH group also interacts intramolecularly with a sulfonyl O atom. This interaction, which strengthens upon ab initio optimization, may influence the chemical environment of the bioactive quinol moiety. In vivo, significant antitumor activity was recorded (day 28) in mice bearing subcutaneously implanted MDA-MB-435 xenografts, following intraperitoneal treatment of mice with compound 1a at 50 mg/kg.

4-Substituted 4-hydroxycyclohexa-2,5-dien-1-ones with selective activities against colon and renal cancer cell lines.

The synthesis and antitumor evaluation of a series of new heteroaromatic- and aromatic-substituted hydroxycyclohexadienones ("quinols"), and their imine counterparts, are described. The quinols were synthesized via the addition of a lithiated aromatic moiety to a quinone ketal followed by deprotection. When the aromatic portion of the molecule is a fused heterobicyclic structure (e.g., benzothiazole derivative 7a), potent in vitro antitumor activity was observed in HCT 116 (GI50 = 40 nM) and HT 29 (GI50 = 380 nM) human colon as well in as MCF-7 and MDA 468 human breast cancer cell lines. When examined on the NCI Developmental Therapeutics Screening Program in vitro screen (60 human cancer cell lines), active compounds in this series consistently displayed a highly unusual pattern of selectivity; cytotoxicity (LC50) was concentrated in certain colon and renal cell lines only. Analogue 7a also showed in vivo antitumor activity against human RXF 944XL renal xenografts in nude NMRI mice and is the focus of further study.

Synthesis and biological evaluation of an N10-Psec substituted pyrrolo[2,1-c][1,4]benzodiazepine prodrug.

The first example of an N10-protected (e.g., Psec, 15) pyrrolo[2,1-c][1,4]benzodiazepine (PBD) analogue that retains significant cytotoxicity in a number of tumour cell lines is reported. This prototype could lead to a new generation of clinically useful N10-protected PBD prodrugs.

Self-schematic representation of the type A and B behavior patterns.

Past research has established clear behavioral differences between Type A and B individuals. The purpose of our research was to examine how these behavioral differences are represented in the self-definitions of Type As and Bs. We investigated the existence of Type A and B self-schemata by using two tasks designed to measure the influence of these hypothetical structures on speed of processing and memory interference. During an initial task, Type As and Bs made self-relevant decisions (like me, not like me) in response to trait adjectives previously scaled as Type A, Type B, or neutral in content. Reaction times for the decisions were measured, and results indicated that both Type As and Bs made faster decisions for schema-compatible responses than for schema-incompatible responses. On a second task, Type As and Bs were tested for recognition memory after they attempted to memorize half of the aforementioned trait list. Memory errors were examined and indicated that Type As and Bs made more errors that were compatible with their respective self-schemata. Taken together, these results indicate that a Type A and B distinction forms a reliable organizing framework for the self-definitions of Type As and Bs. The existence of stable cognitive structures that parallel the behavioral differences between Type As and Bs has important implications for both theory and application.