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Fostering students' competence in applying interdisciplinary knowledge to solve problems has been recognized as an important and challenging issue globally. This is why STEM (Science, Technology, Engineering, Mathematics) education has been emphasized at all levels in schools. Meanwhile, the use of robotics has played an important role in STEM learning design. The purpose of this study was to fill a gap in the current review of research on Robotics-based STEM (R-STEM) education by systematically reviewing existing research in this area. This systematic review examined the role of robotics and research trends in STEM education. A total of 39 articles published between 2012 and 2021 were analyzed. The review indicated that R-STEM education studies were mostly conducted in the United States and mainly in K-12 schools. Learner and teacher perceptions were the most popular research focus in these studies which applied robots. LEGO was the most used tool to accomplish the learning objectives. In terms of application, Technology (programming) was the predominant robotics-based STEM discipline in the R-STEM studies. Moreover, project-based learning (PBL) was the most frequently employed learning strategy in robotics-related STEM research. In addition, STEM learning and transferable skills were the most popular educational goals when applying robotics. Based on the findings, several implications and recommendations to researchers and practitioners are proposed. [ABSTRACT FROM AUTHOR]

This study used Hofstede's cultural dimensions theory to examine Generation Z investors' socially responsible investment perceptions, utilizing data collected from Taiwan and the United States. Generation Z is the most global and socially empowered generation in history, and whether social responsibility appeals to Generation Z warrants investigation. Of 412 questionnaires collected in the United States, 380 were usable, and of 475 collected in Taiwan, 439 were usable. This study exained four variables, namely nationality, gender, work experience, and share ownership; these variables affected how the participants in this study understood and accepted the concept of socially responsible investment. These results provide interesting insight into Generation Z's pro-social attitudes, Perceived consumer effectiveness and trust. This paper suggests implications for cross-cultural study theory and practice, as well as future research directions. [ABSTRACT FROM AUTHOR]

The size and diversity of the Hispanic population in the United States has dramatically increased, with vast implications for health research. We conducted a systematic review of the characterization of the Hispanic population in health research and described its implications. Relevant studies were identified by searches of PubMed, Embase Scopus, and Science/Social Sciences Citation Index from 2000 to 2011. 131 articles met criteria. 56 % of the articles reported only 'Hispanic' or 'Latino' as the characteristic of the Hispanic research population while no other characteristics were reported. 29 % of the articles reported language, 27 % detailed country of origin and 2 % provided the breakdown of race. There is great inconsistency in reported characteristics of Hispanics in health research. The lack of detailed characterization of this population ultimately creates roadblocks in translating evidence into practice when providing care to the large and increasingly diverse Hispanic population in the US. [ABSTRACT FROM AUTHOR]

To aid in understanding the contribution of exterior dust/soil lead to postintervention interior dust lead, a subset of housing from the HUD Lead-Based Paint Hazard Control Grant Program Evaluation was selected for study. Housing from 12 state and local governments was included. Exterior entry and street dust samples were obtained by a vacuum method, and soil samples were building perimeter core composites. Interior dust wipe lead data ( μg/ft²) and paint lead data (mg/cm²) were also available for each of the dwelling units and included in the modeling. Results from 541 dwelling units revealed a wide range of exterior dust and soil lead levels, within and between grantees. Minimum and maximum geometric mean lead levels, by grantee, were 126 and 14,400 μg/ft² for exterior entry dust; 325 and 4, 610 μg/ft² for street dust; and, for soil concentration, 383 and 2640 ppm. Geometric mean exterior entry dust lead concentration (1641 ppm) was almost four times as high as street dust lead concentration (431 ppm), suggesting that lead dust near housing was often a source of street dust lead. Geometric mean exterior entry dust lead loading was more than four times as high as window trough dust lead loading and more than an order of magnitude higher than interior entry dust lead loading.
Statistical modeling revealed pathways from exterior entry dust lead loading to loadings on interior entryway floors, other interior floors, and windowsills. Paint lead was found to influence exterior entry dust lead. Results of this study show that housing where soil lead hazard control activities had been performed had lower postintervention exterior entry, interior entry floor, windowsills, and other floor dust loading levels. Soil was not present for almost half the buildings. Statistical analysis revealed that exterior strategy influenced soil lead concentration, and soil lead concentration influenced street dust lead loading. This study represents one of the few where an impact of soil treatments on dust lead levels within the housing has been documented and may represent the first where an impact on exterior entry dust lead has been found. The inclusion of measures to mitigate the role of exterior sources in lead hazard control programs needs consideration. [ABSTRACT FROM AUTHOR]

Abstract: The Evaluation of the US Department of Housing and Urban Development Lead-Based Paint Hazard Control Grant Program studied the effectiveness of the housing intervention performed in reducing the blood lead of children at four post-intervention times (6-months, 1-year, 2-years, and 3-years). A repeat measures analysis showed that blood lead levels declined up to three-years post-intervention. The results at each successive collection time were significantly lower than at the previous post-intervention time except for the difference between the levels at two and three years. At two-years post-intervention, geometric mean blood lead levels were approximately 37% lower than at pre-intervention. Children with pre-intervention blood lead levels as low as 10μg/dL experienced substantial declines in blood lead levels. Previous studies have found substantial improvements only if a child''s pre-intervention blood lead level was above 20μg/dL. Individual interior lead hazard control treatments as grouped by Interior Strategy were not a significant predictor of post-intervention blood lead levels. However, children living in dwellings where exterior lead hazard control interventions were done had lower blood lead levels at one-year post-intervention than those living in dwellings without the exterior interventions (all other factors being equal), but those differences were only significant when the mean exterior paint lead loading at pre-intervention was about the 90th percentile (7.0mg/cm2). This observation suggests that exterior lead hazard control can be an important component of a lead hazard control plan. Children who were six to eleven months of age at pre-intervention had a significant increase in blood lead at one-year post-intervention, probably due to other exposures. [Copyright &y& Elsevier]

Abstract: The US Department of Housing and Urban Development (HUD) undertook an evaluation of its Lead Hazard Control Grant Program between 1994 and 1999. The Evaluation is the largest study ever done on the effectiveness of lead hazard controls implemented in residential dwellings. The Evaluation had several major objectives: determining the effectiveness of various lead hazard controls in reducing residential dust lead levels and children''s blood lead levels, establishing the costs of doing lead hazard control work and factors that influence those costs, determining the rate of clearance testing failures and their causes, and identifying possible negative effects of lead hazard control work on children''s blood lead levels. This paper reports the overall research design and data collection methods of the Evaluation. The large number of dwelling units enrolled in the Evaluation was possible only by the innovative partnership among HUD, the Evaluators, and the grantees. HUD and the Evaluators relied on the grantees for essentially all of the data collection. The 14 participating HUD Lead Hazard Control Grantees were responsible for implementing the lead hazard control programs in their communities and collecting the study data. This paper describes the methods for recruiting and enrolling dwellings and families, collecting environmental and housing data, interviewing participating families, and collecting data on lead hazard control work performed and its costs. The paper also describes the basic quality control and quality assurance procedures used. The principal outcome measures were lead in dust collected using wipes from floors, window sills, and window troughs and lead in blood collected from children who were 6 years old or younger at enrollment. Data collection was conducted before intervention, immediately postintervention, and 6 and 12 months postintervention. For a subset of dwellings undergoing an extended follow-up data were also collected at 24 and 36 months postintervention. This paper provides the context for subsequent reports that will describe such findings as the influence of lead hazard control work on serial dust lead levels, the influence of lead hazard control work on serial blood lead levels in children, the nature and costs of the lead hazard control work done at the dwellings, and the experience of the grantees in meeting clearance testing requirements. [Copyright &y& Elsevier]

Abstract: From 1994 to 1999, the Evaluation of the US Department of Housing and Urban Development Lead-Based Paint Hazard Control Grant Program studied the intervention experiences of over 2800 homes in 11 states in the USA. Each interior intervention was categorized as (in order of increasing intensity) (a) cleaning/spot painting; (b) complete repainting; (c) complete repainting plus window treatments; (d) window abatement plus treatments to other components; (e) abatement of all lead-based paint hazards; or (f) abatement of all lead-based paint. Complete dust testing and environmental data were available for 1034 and 278 dwellings through 12 and 36 months postintervention, respectively. Strategies ranging from complete repainting to window abatement plus other treatments reduced geometric mean preintervention windowsill and floor dust lead loadings up to 36 months postintervention (reductions for complete repainting, from 16 to 5μg/ft2 on floors and 182 to 88μg/ft2 on sills; for window abatement plus other treatments, 27–8μg/ft2 on floors and 570–124μg/ft2 on sills). Full abatement reduced windowsill and floor loadings from baseline to 12 months postintervention [95–6μg/ft2 on floors and 518–30μg/ft2 on sills (data were not available for this strategy at 36 months)]. Window lead-hazard abatement was the most effective measure to reduce dust lead loadings on windows, but this treatment would need to be performed in conjunction with treatments to floors as well as exterior and soil treatments for the most effective control of dust lead on floors. [Copyright &y& Elsevier]

• A high-salt diet induces hypertension, which eventually leads to cardiovascular remodeling. • High-salt induced hypertensive mice have obvious oxidative stress and endothelial dysfunction. • As a prescription that has been used in clinical practice for many years,Xin-Ji-Er-Kanghas the function of antioxidant and balance endothelin system. • XJEK mitigates cardiac remodeling in high-salt-induced hypertensive mice. Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula that has beenreported to exert effective protection against cardiovascular diseases, such as hypertension and myocarditis. The aim of the present study was to investigate the effect of XJEK on high-salt-induced hypertensive mice and its possible mechanism. The model of hypertension was established through a high-salt diet. Sixty male Kunming mice were randomized into six groups, namely the Control, Model, Low-dose XJEK, Middle-dose XJEK, High-dose XJEK and Fosinopril groups (n= 10 per group). Different steady interventions were given to each group: 0.9% Sodium chloride was added to the diet of the Control group and 8% sodium chloride to the diet of the other five groups from the very beginning. An additional 4, 8 and 12 g/kg/day XJEK were intragastrically administered to the Low-dose, Middle-dose and High-dose XJEK groups, respectively, and 2 mg/kg/day fosinopril to the fosinopril group, from the start of week 5. Systolic blood pressure (SBP) was measured weekly from weeks 1 to 8 using the tail-cuff method. At the end of week 8, left ventricular (LV) systolic pressure, LV end-diastolic pressure and rate of rise of LV pressure were examined using a TransonicScisense catheter (Transonic Systems Inc,Ithaca, NY,USA). Endothelium-dependent relaxations induced by acetylcholine were observed in an isolated thoracic aorta ring. Serum and heartsweresampled for the measurement of the following indexes:Serum nitric oxide (NO), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content (determined by colorimetricanalysis); serum angiotensin II(Ang II), endothelin-1, endothelial NO synthase (eNOS), asymmetric dimethylarginine (ADMA), tetrahydrobiopterin (BH 4) concentration and l -arginine (determined by enzyme-linked immunosorbent assay); heart to body weight (HW/BW) ratio; myocardial morphological change (determined by HE and VG staining); myocardial eNOS expression (determined by immunofluorescence), and myocardial endothelin receptor A (ET A) expression (determined by western blotting). Results:Statistical data showed that the HW/BW ratio was significantly decreased in the drug treatment group. XJEK treatment could improve the heart systolic and diastolic function and ameliorate hemodynamic parameters and vascular remodeling indexes. Colorimetric results showed that, compared with the model group, XJEK increased serum SOD, NOlevels, and decreased those of serum MDA and Ang II. XJEK reverted changes in cardiac pathology, decreased the myocardial cross-sectional area, collagen volume fraction and perivascular collagen area and improved endothelial dysfunction (ED) by promoting eNOS activity, enhancing NO bioavailability, increasing the expression of BH 4 and decreasing ET A content. In addition, treatment with XJEK decreased ADMA content in the myocardium. Conclusion:In conclusion, XJEK mitigates cardiac remodeling in high-salt-induced hypertensive mice. The potential mechanism involves improved oxidative stress and endothelial dysfunction, independently of ameliorating BP. [ABSTRACT FROM AUTHOR]

Poly(ADP-ribose) polymerase (PARP) inhibitors have demonstrated promising clinical activity in multiple cancers. However, resistance to PARP inhibitors remains a substantial clinical challenge. In the present study, we report that anaplastic lymphoma kinase (ALK) directly phosphorylates CDK9 at tyrosine-19 to promote homologous recombination (HR) repair and PARP inhibitor resistance. Phospho-CDK9-Tyr19 increases its kinase activity and nuclear localization to stabilize positive transcriptional elongation factor b and activate polymerase II-dependent transcription of HR-repair genes. Conversely, ALK inhibition increases ubiquitination and degradation of CDK9 by Skp2, an E3 ligase. Notably, combination of US Food and Drug Administration-approved ALK and PARP inhibitors markedly reduce tumor growth and improve survival of mice in PARP inhibitor-/platinum-resistant tumor xenograft models. Using human tumor biospecimens, we further demonstrate that phosphorylated ALK (p-ALK) expression is associated with resistance to PARP inhibitors and positively correlated with p-Tyr19-CDK9 expression. Together, our findings support a biomarker-driven, combinatorial treatment strategy involving ALK and PARP inhibitors to induce synthetic lethality in PARP inhibitor-/platinum-resistant tumors with high p-ALK-p-Tyr19-CDK9 expression., (© 2022. The Author(s).)

Underserved populations, including those from racial and ethnic groups and with low socioeconomic status, often lack access to mobile apps aimed at reducing health risk factors. This study evaluated the feasibility, acceptability, and preliminary effectiveness of the mobile app, My Wellness Coach (MWC), designed to promote behavior change in seven core areas of integrative health among underserved populations. Patients and staff were recruited from clinic and other settings. Some participants used MWC in a weekly group setting (n = 5); others on their own with support from a coordinator (n = 36). Health outcomes were assessed at baseline and 3 months. Mobile app ratings were collected at 5 weeks and 3 months. Goal setting data were analyzed at 3 months. Most participants (76%) set at least one goal, 71% created action steps for goals, and 29% completed a goal. Patients in the group setting had the highest rate of goal completion (60%) compared to patients (20%) and staff (27%) using the app on their own. Significant (p < .05) changes in pre- and post-test scores were documented for overall wellbeing, global physical health, BMI, vigorous physical activity, and eHealth literacy. Most participants (75%-91%) gave MWC high ratings for impact on behavior change, help seeking, intent to change, attitudes, knowledge, and awareness. This study documented preliminary evidence of the potential benefits of MWC among underserved communities. Future evaluations of Spanish and Android versions and comparisons between group and individual administration will inform implementation strategies for scaling MWC-based interventions to reach underserved communities nationally., (© Society of Behavioral Medicine 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

One of the most effective approaches to improve resource usage efficiency and degree of resource collecting is to integrate resources. Many studies on the integration of information resources are also available. The search engines are the most well-known. At the same time, this article intends to optimize the integration of British and American literature information resources by employing distributed cloud computing, based on the needs of British and American literature. This research develops a model for the dispersed nature of cloud computing. It optimizes the method by fitting the mathematical model of transmission cost and latency. This article analyzes the weaknesses of the current British and American literature information resource integration and optimizes them for the integration of British and American literature resources. The Random algorithm has the longest delay, according to the results of this paper's experiments (maximum user weighted distance). The algorithms NPA-PDP and BWF have longer delays than the algorithm Opt. The percentage decline varies between 0.17 percent and 1.11 percent for different algorithms. It demonstrates that the algorithm presented in this work can be used to integrate and maximize information resources from English and American literature., Competing Interests: The author does not have any possible conflicts of interest., (Copyright © 2022 Mei Chen.)

Importance: Due to the evolving variants of coronavirus disease 2019 (COVID-19), it is important to understand the relationship between the disease condition and socioeconomic, demographic, and health indicators across regions., Background: Studies examining the relationships between infectious disease and socioeconomic variables are not yet well established., Design: A total of 3042 counties in the United States are included as the observation unit in the study. Two outcome variables employed in the study are the control of disease spread and infection prevalence rates in each county., Method: Data are submitted to quantile regression, hierarchical regression, and random forest analyses to understand the extent to which health outcomes are affected by demographics, socioeconomics, and health indicators., Results: Counties with better control of the disease spread tend to have lower infection rates, and vice versa. When measuring different outcome variables, the common risk factors for COVID-19 with a 5% level of statistical significance include employment ratio, female labor ratio, young population ratio, and residents' average health risk factors, while protective factors include land size, housing value, travel time to work, female population ratio, and ratio of residents who identify themselves as mixed race., Conclusions: The implications of the findings are that the ability to maintain social distancing and personal hygiene habits are crucial in deterring disease transmission and lowering incidence rates, especially in the early stage of disease formation. Relevant authorities should identify preventive factors and take early actions to fight infectious diseases in the future.

Significance: Since the last Food and Drug Administration (FDA) approval of a wound healing therapeutic in 1997, no new therapeutic candidate (excluding physical therapies, devices, dressings, and antimicrobial agents) has advanced to clinical applications. During this period, the FDA drug approvals for tumors, which have been referred to as "wounds that do not heal," have reached a total of 284 (by end of 2018). Both political and scientific factors may explain this large discrepancy in drug approvals for the two seemingly related and equally complex pathophysiological conditions. Recent Advances: Using the current research funding ratio of 1:150 for wound healing to cancer and the 5% FDA drug approval rate for oncology, we reach a crude estimate of a 0.03% success rate for wound healing therapeutics. Unless a drastic improvement of the current situation, we express a pessimistic outlook toward new and effective wound healing drugs. Critical Issues: We argue that successful development of wound healing therapeutics will rely on identification of wound healing driver genes (WDGs), and the focus should be on WDGs for the wound closure phase of wound healing. Therefore, WDGs must be both necessary and sufficient for wound closure; the absence of a WDG disrupts wound closure, while its supplementation alone is sufficient to restore full wound closure. Successful translation of a WDG into therapeutics requires availability of well-defined animal models with a high degree of relevance to humans. This review discusses the main hurdles faced by the wound healing research community behind the development of so-called "rescuing drugs" for wound healing. Future Directions: Given the lack of new wound healing drugs for the past 23 years, there is a need for a wide range of fresh, innovative, and thorough debates on wound healing drug development, including an organized movement to raise public support for wound healing research.

The Center for Drug Evaluation and Research (CDER) within the US Food and Drug Administration (FDA) is tracking the use of nanotechnology in drug products by building and interrogating a technical profile of products containing nanomaterials submitted to CDER. In this Analysis, data from more than 350 products show an increase in the submissions of drug products containing nanomaterials over the last two decades. Of these, 65% are investigational new drugs, 17% are new drug applications and 18% are abbreviated new drug applications, with the largest class of products being liposomal formulations intended for cancer treatments. Approximately 80% of products have average particle sizes of 300 nm or lower. This analysis identifies several trends in the development of drug products containing nanomaterials, including the relative rate of approvals of these products, and provides a comprehensive overview on the landscape of nanotechnology application in medicine.

The National Institutes of Health (NIH) is the largest source of funding for biomedical research in the world. This funding is largely effected through a competitive grants process. Each year the Center for Scientific Review (CSR) at NIH manages the evaluation, by peer review, of more than 55,000 grant applications. A relevant management question is how this scientific evaluation system, supported by finite resources, could be continuously evaluated and improved for maximal benefit to the scientific community and the taxpaying public. Towards this purpose, we have created the first system-level description of peer review at CSR by applying text analysis, bibliometric, and graph visualization techniques to administrative records. We identify otherwise latent relationships across scientific clusters, which in turn suggest opportunities for structural reorganization of the system based on expert evaluation. Such studies support the creation of monitoring tools and provide transparency and knowledge to stakeholders.

Highly variable (HV) drugs are defined as those for which within-subject variability (%CV) in bioequivalence (BE) measures is 30% or greater. Because of this high variability, studies designed to show whether generic HV drugs are bioequivalent to their corresponding HV reference drugs may need to enroll large numbers of subjects even when the products have no significant mean differences. To avoid unnecessary human testing, the US Food and Drug Administration's Office of Generic Drugs developed a reference-scaled average bioequivalence (RSABE) approach, whereby the BE acceptance limits are scaled to the variability of the reference product. For an acceptable RSABE study, an HV generic drug product must meet the scaled BE limit and a point estimate constraint. The approach has been implemented successfully. To date, the RSABE approach has supported four full approvals and one tentative approval of HV generic drug products.

Regulatory approaches for evaluating therapeutic equivalence of multisource (or generic) drug products vary among different countries and/or regions. Harmonization of these approaches may decrease the number of in vivo bioequivalence studies and avoid unnecessary drug exposure to humans. Global harmonization for regulatory requirements may be promoted by a better understanding of factors underlying product performance and expectations from different regulatory authorities. This workshop provided an opportunity for pharmaceutical scientists from academia, industry and regulatory agencies to have open discussions on current regulatory issues and industry practices, facilitating harmonization of regulatory approaches for establishing therapeutic equivalence and interchangeability of multisource drug products., (Published by Elsevier B.V.)

Assessment of bioavailability/bioequivalence generally relies on the comparison of rate and extent of drug absorption between products. Rate of absorption is commonly expressed by peak concentration (C(max)) and time to peak concentration (T(max)), although these parameters are indirect measures of absorption rate. Recognizing the importance of systemic exposure to drug efficacy and safety, FDA recommended that systemic exposure be better used for bioavailability/bioequivalence assessment. Apart from peak exposure and total exposure, FDA also recommended a new metric for early exposure that is considered necessary when a control of input rate is critical to ascertain drug efficacy and/or safety profile. The early exposure can be measured by truncating the area under the curve at T(max) of the reference product (PAUC(r,tmax)) or some designated early time after dosing. The choice of truncation is most appropriately based on PK/PD relationship or efficacy/safety data for the drug under examination. Compared with C(max), PAUC(r,tmax) has higher sensitivity in detecting formulation differences and may be more variable. If the metric is highly variable, the reference-scaling approach can be employed for bioequivalence evaluation. The partial area metric is useful in PK/PD characterization as well as in the evaluation of bioavailability, bioequivalence and/or comparability.

Background: To promote results in the National Lung Screening Trial (NLST) that are generalizable across the entire US population, a subset of NLST sites developed dedicated strategies for minority recruitment., Purpose: To report the effects of targeted strategies on the accrual of underrepresented groups, to describe participant characteristics, and to estimate the costs of targeted enrollment., Methods: The 2002-2004 Tobacco Use Supplement was used to estimate eligible proportions of racial and ethnic categories. Strategic planning included meetings/conferences with key stakeholders and minority organizations. Potential institutions were selected based upon regional racial/ethnic diversity and proven success in recruitment of underrepresented groups. Seven institutions submitted targeted recruitment strategies with budgets. Accrual by racial/ethnic category was tracked for each institution. Cost estimates were based on itemized receipts for minority strategies relative to minority accrual., Results: Of 18,842 participants enrolled, 1576 (8.4%) were minority participants. The seven institutions with targeted recruitment strategies accounted for 1223 (77.6%) of all minority participants enrolled. While there was a significant increase in the rate of minority accrual pre-implementation to post-implementation for the institutions with targeted recruitment (9.3% vs. 15.2%, p <  0.0001), there was no significant difference for the institutions without (3.5% vs. 3.8%, p = 0.46). Minority enrollees at the seven institutions tended to have less than a high school education, be economically disadvantaged, and were more often uninsured. These socio-demographic differences persisted at the seven institutions even after adjusting for race and ethnicity. The success of different strategies varied by institution, and no one strategy was successful across all institutions. Costs for implementation were also highly variable, ranging from $146 to $749 per minority enrollee., Limitations: Data on minority recruitment processes were not consistently kept at the individual institutions. In addition, participant responses via newspaper advertisements and the efforts of minority staff hired by the institutions could not be coded on Case Report Forms., Conclusions: Strategic efforts were associated with significant increases in minority enrollment. The greatest successes require that a priori goals be established based on eligible racial/ethnic proportions; the historical performance of sites in minority accrual should factor into the selection of sites; recruitment planning must begin well in advance of trial launch; and there must be endorsement by prominent representatives of the racial groups of interest.

The use of lipid-based dosage forms for enhancement of drug absorption or delivery has drawn considerable interest from pharmaceutical scientists. The unique characteristics of these dosage forms, however, present significant challenges to pharmaceutical industry and regulatory agencies in many ways. For example, safety assessment is necessary when the use of a new lipid excipient is considered. An important question for lipid formulation is whether the drug remains in solubilised form along the gastrointestinal (GI) tract after it is administered. Certain lipid excipients and surfactants have been reported to change intestinal permeability or interfere with enzyme/transporter activity, thereby affecting drug bioavailability. The potential influence of biopharmaceutical and/or pathophysiological factors on the drug or lipid excipient(s) needs to be explored. For a complex lipid-based dosage form, the conventional in vitro dissolution methods may not be appropriate for predicting in vivo performance in view of the convoluted GI processing of the lipid vehicle and formulation Of paramount importance is to identify any gaps in the scientific understanding of lipid-based dosage forms so that regulatory issues can be addressed. More mechanistic studies should be encouraged to facilitate a better understanding of the pharmaceutical characteristics of lipid formulations and complex interactions between lipid excipient, drug and physiological environment. This review discusses some regulatory considerations in the use of lipid excipients and delivery systems for pharmaceutical development. Implications in the regulatory determination of pharmaceutical equivalence, bioequivalence and therapeutic equivalence are also illustrated.

Over the past decade, concerns have been expressed increasingly regarding the difficulty for highly variable drugs and drug products (%CV greater than 30) to meet the standard bioequivalence (BE) criteria using a reasonable number of study subjects. The topic has been discussed on numerous occasions at national and international meetings. Despite the lack of a universally accepted solution for the issue, regulatory agencies generally agree that an adjustment of the traditional BE limits for these drugs or products may be warranted to alleviate the resource burden of studying relatively large numbers of subjects in bioequivalence trials. This report summarizes a careful examination of all the statistical methods available and extensive simulations for BE assessment of highly variable drugs/products. Herein, the authors present an approach of scaling an average BE criterion to the within-subject variability of the reference product in a crossover BE study, together with a point-estimate constraint imposed on the geometric mean ratio between the test and reference products. The use of a reference-scaling approach involves the determination of variability of the reference product, which requires replication of the reference treatment in each individual. A partial replicated-treatment design with this new data analysis methodology will thus provide a more efficient design for BE studies with highly variable drugs and drug products.

At the conclusion of most lead hazard control interventions in federally assisted housing built before 1978, a certified clearance examiner must verify that the lead hazard control work was completed as specified and that the area is safe for residents, a process referred to as clearance. This study explores the experience of 14 grantees participating in the Evaluation of the HUD Lead-Based Paint Hazard Control Grant Program in passing clearance. The study also considers how preintervention lead levels (interior dust and paint), building condition/characteristics, and the scope of work influenced initial clearance dust lead loadings and clearance rates. At the initial clearance inspection, 80% of the 2682 dwellings achieved grantee-specific clearance standards on windowsills, window troughs (500 microg/ft2 and 800 microg/ft2, respectively), and floors (80, 100, or 200 microg/ft2 depending on state/local regulations at the dates of clearance in the mid-1990s), with individual grantee success rates ranging from 63 to 100%. Dwellings that failed initial clearance required an average of 1.13 retests to clear. The high level of success at clearance demonstrates that following methods for work site containment, lead hazard control, and cleaning similar to those recommended in the HUD Guidelines for the Evaluation and Control of Lead-Based Paint in Housing is effective. The most common lead hazard control intervention was window abatement accompanied by the repair or abatement of all other deteriorated lead-based paint (56% of dwellings). An additional 5% of dwellings were fully abated, 29% had lower intensity interventions. Interventions including window replacement are recommended to reduce dust lead loading on windowsills and troughs at clearance, but lower level interventions such as full paint stabilization are just as good at reducing floor dust lead loadings. Whatever lead hazard control activities are selected, the condition of the surfaces of interest should be in good condition at clearance.

This study designed a modified light path of a phase-contrast microscope to evaluate the feasibility of fiber counting on a television screen (TVS). A comparison also was made of the fiber counts, fiber density, and precision derived from repeatedly counting fibers through eyepieces (EPs) and on a TVS connected to a phase contrast microscope. Thirty asbestos fiber samples were counted 10 times repeatedly. Ten samples were counted by viewing the same field through an EP and on a TVS alternately, whereas the other 20 samples were counted separately by using an EP and a TVS. The A rules of National Institute for Occupational Safety and Health (NIOSH) 7400 method was quoted. No statistically significant difference of fiber density (p = 0.39) or fiber counts (p > 0.05) was observed between the TVS and EP methods, though TVS gave a slightly lower value than EP did. The bias of the two methods was 7.7 +/- 8.0% on an average. The relative standard deviations (RSDs) for both methods were the same, 0.40, which resembled the theoretical RSD, 0.44, of NIOSH 7400. Meanwhile, the theoretical and experimental RSDs were not significantly different for either method (p > 0.05). The modified light path of a phase contrast microscope provided a compatible view with less eye strain on a TVS than a conventional EP. Moreover, operator biases and variability might be greatly reduced by training several counters simultaneously on the TVS.

Data from an evaluation of the HUD Lead Hazard Control Grant Program were used to evaluate the prevalence and location of teeth marks on painted surfaces in residential housing. The results of these analyses will be useful in the development of more effective pediatric lead poisoning prevention programs. These programs have historically placed considerable emphasis on surfaces accessible to children for mouthing activities. This study analyzes the largest set of data ever assembled on the prevalence of teeth marks in housing. Data from 308,851 observations in 3,454 housing units were analyzed to determine the prevalence of teeth mark observations per surface, dwelling unit, and building component, and by housing age, inspector, and grantee. An average of 4.0 teeth marks per 10,000 surfaces with paint-lead greater than or equal to 1.0 mg/cm2 were observed. For surfaces with less than 1.0 mg/cm2 lead the rate was 1.5 teeth marks/10,000 surfaces. The number of teeth marks per 10,000 surfaces increased with age of housing for surfaces with 1.0 mg/cm2 or higher lead but not for surfaces with less than 1.0 mg/cm2 lead. Teeth mark observation rates were 36 times higher for windowsills than for other components and ranged up to 11 per 10,000 surfaces and 9 dwellings per 100 dwelling units for 2 grantees with the highest rates. Blood lead levels in children exhibiting moderate to high mouthing behavior were higher than in children without such behavior, especially in housing where teeth marks were observed. Special priority should be given to windowsills when making decisions on lead hazard control for "accessible," "chewable," or "mouthable" surfaces.

The current BSC guidance issued by the FDA allows for biowaivers based on conservative criteria. Possible new criteria and class boundaries are proposed for additional biowaivers based on the underlying physiology of the gastrointestinal tract. The proposed changes in new class boundaries for solubility and permeability are as follows: 1. Narrow the required solubility pH range from 1.0-7.5 to 1.0-6.8. 2. Reduce the high permeability requirement from 90% to 85%. The following new criterion and potential biowaiver extension require more research: 1. Define a new intermediate permeability class boundary. 2. Allow biowaivers for highly soluble and intermediately permeable drugs in IR solid oral dosage forms with no less than 85% dissolved in 15 min in all physiologically relevant dissolution media, provided these IR products contain only known excipients that do not affect the oral drug absorption. The following areas require more extensive research: 1. Increase the dose volume for solubility classification to 500 mL. 2. Include bile salt in the solubility measurement. 3. Use the intrinsic dissolution method for solubility classification. 4. Define an intermediate solubility class for BCS Class II drugs. 5. Include surfactants in in vitro dissolution testing.