Combining Isolation-Free and Co-Processing Manufacturing Approaches to Access Room Temperature Ionic Liquid Forms of APIs.

The addition of non-active components at the point of active pharmaceutical ingredient (API) isolation by means of co-processing is an attractive approach for improving the material properties of APIs. Simultaneously, there is increased interest in the pharmaceutical industry in continuous manufacturing processes. These often consist of liquid feeds which maintain materials in solution and mean that solids handling is avoided until the final step. Such techniques enable new forms of APIs to be used in final dosage forms which have been overlooked due to unfavourable material properties. API-based ionic liquids (API-ILs) are an example of a class of compounds that exhibit exceptional solubility and stability qualities at the cost of their physical characteristics. API-ILs could benefit from isolation-free manufacturing in combination with co-processing approaches to circumvent handling issues and make them viable routes to formulating poorly soluble APIs. However, API-ILs are most commonly synthesised via a batch reaction that produces an insoluble solid by-product. To avoid this, an ion exchange resin protocol was developed to enable the API-IL to be synthesised and purified in a single step, and also produce it in a liquid effluent that can be integrated with other unit operations. Confined agitated bed crystallisation and spray drying are examples of processes that have been adapted to produce or consume liquid feeds and were combined with the ion exchange process to incorporate the API-IL synthesis into isolation-free frameworks and continuous manufacturing streams. This combination of isolation-free and co-processing techniques paves the way towards end-to-end continuous manufacturing of API-IL drug products.

Integrated Purification and Formulation of an Active Pharmaceutical Ingredient via Agitated Bed Crystallization and Fluidized Bed Processing.

Integrated API and drug product processing enable molecules with high clinical efficacy but poor physicochemical characteristics to be commercialized by direct co-processing with excipients to produce advanced multicomponent intermediates. Furthermore, developing isolation-free frameworks would enable end-to-end continuous processing of drugs. The aim of this work was to purify a model API (sodium ibuprofen) and impurity (ibuprofen ethyl ester) system and then directly process it into a solid-state formulation without isolating a solid API phase. Confined agitated bed crystallization is proposed to purify a liquid stream of impure API from 4% to 0.2% w/w impurity content through periodic or parallelized operations. This stream is combined with a polymer solution in an intermediary tank, enabling the API to be spray coated directly onto microcrystalline cellulose beads. The spray coating process was developed using a Design of Experiments approach, allowing control over the drug loading efficiency and the crystallinity of the API on the beads by altering the process parameters. The DoE study indicated that the solvent volume was the dominant factor controlling the drug loading efficiency, while a combination of factors influenced the crystallinity. The products from the fluidized bed are ideal for processing into final drug products and can subsequently be coated to control drug release.

Catecholamines in neuroblastoma: Driver of hypertension, or solely a marker of disease?

BACKGROUND: Neuroblastoma is a common solid tumor of childhood and is often associated with hypertension. Potential etiologies contributing to hypertension include renal compression, pain, volume overload, and catecholamine secretion. CASES: We completed a single center retrospective review of children with neuroblastoma and ≥stage II hypertension (per Hypertension Canada guidelines) over a 2-year period. All patients (n = 10) had elevated urine normetanephrine levels and eight had intra-abdominal tumors. Four patients had refractory hypertension requiring > three agents, of which three required alpha/beta blockade. CONCLUSION: Although multifactorial, hypertension in neuroblastoma often has a neuroendocrine component. Excess normetanephrine production in neuroblastoma may be a more common hypertensive mechanism than previously appreciated. Urinary normetanephrine elevation could suggest potential neuroendocrine-mediated hypertension.

Design of a Combined Modular and 3D-Printed Falling Film Solution Layer Crystallizer for Intermediate Purification in Continuous Production of Pharmaceuticals.

A highly scalable combined modular and 3D-printed falling film crystallization device is developed and demonstrated herein; the device uses a small, complex, printed overflow-based film distribution part that ensures formation of a well-distributed heated liquid film around a modular, tubular residence time/crystallizer section, enabling extended residence times to be achieved. A model API (ibuprofen) and impurity (ibuprofen ethyl ester) were used as a test system in the evaluation of the novel crystallizer design. The proposed crystallizer was run using three operational configurations: batch, cyclical batch, and continuous feed, all with intermittent removal of product. Results were suitable for intermediate purification requirements, and stable operation was demonstrated over multiple cycles, indicating that this approach should be compatible with parallel semicontinuous operation for intermediate purification and solvent swap applications in the manufacture of drugs.

Emotional Eating in Adults: The Role of Sociodemographics, Lifestyle Behaviors, and Self-Regulation-Findings from a U.S. National Study.

BACKGROUND: Emotional eating, the tendency to overeat in response to negative emotions, has been linked to weight gain. However, scant evidence exists examining the prevalence and correlates of emotional eating among large samples of adults in the United States (U.S.). Hence, we examine the relationship among individual and socioeconomic factors, health behaviors, and self-regulation with emotional eating patterns among U.S. adults. METHODS: Cross-sectional analysis of 5863 Family Health Habits Survey participants. Multivariable, ordered, logistic regression was employed to examine the relationship between the frequency of the desire to eat when emotionally upset (never, rarely, sometimes, often, and very often) and the independent variables. RESULTS: Analysis reveals that 20.5% of the sample tended to emotionally eat often or very often. Being female, non-Hispanic White, and of younger age were all related to a higher likelihood of emotional eating. Additionally, inability to delay gratification (impatience) was related to an 18% increased likelihood (95% confidence interval (CI) 1.05-1.33) for emotional eating. Finally, emotional eating was significantly related to more frequent fast-food consumption. CONCLUSIONS: Program planners might need to develop targeted interventions aimed at enhancing emotional regulation skills while addressing these less healthful behaviors (e.g., fast-food intake) with the goal of obesity and chronic disease prevention.

Heterogeneity in the Effects of Food Vouchers on Nutrition Among Low-Income Adults: A Quantile Regression Analysis.

PURPOSE: To determine whether baseline fruit and vegetable (FV) intake or other predictors are associated with response to food vouchers (change in FV intake) among low-income adults. DESIGN: Secondary analysis of a randomized, 2 x 2-factorial, community-based trial. SETTING: San Francisco, California. SUBJECTS: 359 low-income adults aged ≥21 years old. INTERVENTION: Participants were mailed $20 of food vouchers monthly for 6 months, and randomized to 1 of 4 arms according to: eligible foods (FV only or any foods) and redemption schedule (weekly or monthly). MEASURES: Change in FV intake measured in cup equivalents between baseline and month 6 of the trial, based on 24-hour dietary recalls. ANALYSIS: Quantile multivariate regressions were employed to measure associations between key predictors and change in FV intake across study arms. RESULTS: FV-only weekly vouchers were associated with increased FV intake at the 25th percentile (0.24 cups/day, p = 0.048) and 50th percentile (0.37 cups/day, p = 0.02) of the distribution, but not at lower and higher quantiles. Response to the vouchers diminished 0.10 cups/day for each additional household member (p = 0.02). CONCLUSION: Response to food vouchers varied along the FV intake distribution, pointing to some more responsive groups and others potentially needing additional support to increase FV intake. Larger households likely need vouchers of higher dollar value to result in similar changes in dietary intake as that observed in smaller households.

Evaluating A USDA Program That Gives SNAP Participants Financial Incentives To Buy Fresh Produce In Supermarkets.

Pricing incentives may reduce disparities in obesity among Supplemental Nutrition Assistance Program (SNAP) participants by increasing fruit and vegetable purchases. However, few studies have evaluated the feasibility and effectiveness of those incentives in supermarkets, as opposed to farmers markets. In 2015 and 2016, as part of a US Department of Agriculture (USDA) pilot program, a dollar-matching program in Michigan provided SNAP participants with a subsidy on fresh produce purchases. Using data on millions of individual transactions from thirty-two stores, we found that SNAP participants' spending on fresh produce was significantly higher at stores that implemented the subsidy than at control stores during both intervention periods (7.4 percent and 2.2 percent higher in 2015 and 2016, respectively). Our results highlight the effectiveness and feasibility of dollar-matching programs for fruit and vegetable purchases by SNAP participants who shop at supermarkets, and they support the USDA's expansion of existing programs to that setting in additional states.

The intergenerational transmission of obesity: The role of time preferences and self-control.

Previous research has found that impatient time preferences and self-control problems (present bias) are related to increased obesity risk. However, scant evidence exists pertaining to whether parents' impatience and self-control problems impact the obesity status of their children, too. Accordingly, we explore this study question among a large national sample of US adults and their children. Study results confirm previous findings indicating that intertemporal preferences are related to adults' obesity status. Moreover, these results extend the literature by finding that children of impatient or present-biased parents have a significantly higher likelihood of being obese, too. Specifically, parents' low levels of patience and present bias were each independently related to a five-percentage point increase in the likelihood of obesity of their children. These findings were more pronounced when all children were combined in analyses and for the first child; however, they varied for the second and third child. Thus, findings suggest that parents' time preferences and self-control problems likely affect not only their own weight status but that of their children.

Deal or no deal? The prevalence and nutritional quality of price promotions among U.S. food and beverage purchases.

OBJECTIVE: This study examines trends in the prevalence of price promotions among packaged food and beverage purchases, differences in prevalence by household race/ethnicity or income, and the association between price promotions and the nutritional profile of purchases. DESIGN: This cross-sectional study utilizes a dataset of 90 million purchases from 38,744 (2008) to 45,042 (2012) US households in 2008-2012. Chi-square tests were used to examine whether the proportion of purchases with price promotions changed over time or differed by household race/ethnicity or income. T-tests were used to compare purchased products' nutritional profiles. RESULTS: Prevalence of price promotions among packaged food and beverage purchases increased by 8% and 6%, respectively, from 2008 to 2012, with both reaching 34% by 2012. Higher-income households had greater proportions of purchases with price promotions than lower-income households. Asian households had the highest proportion of purchases with any price promotion, followed by non-Hispanic whites. While total price-promoted packaged food purchases had higher mean energy, total sugar, and saturated fat densities than purchases with no price promotions, absolute differences were small. CONCLUSIONS: Prevalence of price promotions among US household purchases increased from 2008 to 2012 and was greater for higher-income households. No clear associations emerged between presence of price promotions and nutritional quality of purchases.

Galvanic Corrosion of Lead by Iron (Oxyhydr)Oxides: Potential Impacts on Drinking Water Quality.

Lead exposure via drinking water remains a significant public health risk; this study explored the potential effects of upstream iron corrosion on lead mobility in water distribution systems. Specifically, galvanic corrosion of lead by iron (oxyhydr)oxides was investigated. Coupling an iron mineral cathode with metallic lead in a galvanic cell increased lead release by 531 µg L-1 on average-a 9-fold increase over uniform corrosion in the absence of iron. Cathodes were composed of spark plasma sintered Fe3O4 or α-Fe2O3 or field-extracted Fe3O4 and α-FeOOH. Orthophosphate immobilized oxidized lead as insoluble hydroxypyromorphite, while humic acid enhanced lead mobility. Addition of a humic isolate increased lead release due to uniform corrosion by 81 µg L-1 and-upon coupling lead to a mineral cathode-release due to galvanic corrosion by 990 µg L-1. Elevated lead in the presence of humic acid appeared to be driven by complexation, with 208Pb and UV254 size-exclusion chromatograms exhibiting strong correlation under these conditions (R2average = 0.87). A significant iron corrosion effect was consistent with field data: lead levels after lead service line replacement were greater by factors of 2.3-4.7 at sites supplied by unlined cast iron distribution mains compared with the alternative, lined ductile iron.

No Fat, No Sugar, No Salt . . . No Problem? Prevalence of "Low-Content" Nutrient Claims and Their Associations with the Nutritional Profile of Food and Beverage Purchases in the United States.

BACKGROUND: Nutrient claims are a commonly used marketing tactic, but the association between claims and nutritional quality of products is unknown. The objective of this study was to examine trends in the proportion of packaged food and beverage purchases with a nutrient claim, whether claims are associated with improved nutritional profile, and whether the proportion of purchases with claims differs by race/ethnicity or socioeconomic status. METHODS: This cross-sectional study examined nutrient claims on more than 80 million food and beverage purchases from a transaction-level database of 40,000 US households from 2008 to 2012. χ2 Tests were used to examine whether the proportion of purchases with a low/no-content claim changed over time or differed by race/ethnicity or household socioeconomic status. Pooled transactions were examined using t-tests to compare products' nutritional profiles overall and by food and beverage group. RESULTS: Thirteen percent of food and 35% of beverage purchases had a low-content claim. Prevalence of claims among purchases did not change over time. Low-fat claims were most prevalent for both foods and beverages (10% and 19%, respectively), followed by low-calorie (3% and 9%), low-sugar (2% and 8%), and low-sodium (2% for both) claims. Compared to purchases with no claim, purchases with any low-content claim had lower mean energy, total sugar, total fat, and sodium densities. However, the association between particular claim types and specific nutrient densities varied substantially, and purchases featuring a given low-content claim did not necessarily offer better overall nutritional profiles or better profiles for the claimed nutrient, relative to products without claims. In addition, there was substantial heterogeneity in associations between claims and nutrient densities within food and beverage groups. CONCLUSIONS: Variations in nutrient density by claim type and food and beverage group suggests that claims may have differential utility for certain foods or nutrients and, in some cases, may mislead about the overall nutritional quality of the food.

The effect of prices on nutrition: Comparing the impact of product- and nutrient-specific taxes.

This paper provides an analysis of the role of prices in determining food purchases and nutrition using very detailed transaction-level observations for a large, nationally-representative sample of US consumers over the period 2002-2007. Using product-specific nutritional information, we develop a new method of partitioning the product space into relevant nutritional clusters that define a set of nutritionally-bundled goods, which parsimoniously characterize consumer choice sets. We then estimate a large utility-derived demand system over this joint product-nutrient space that allows us to calculate price and expenditure elasticities. Using our structural demand estimates, we simulate the role of product taxes on soda, sugar-sweetened beverages, packaged meals, and snacks, and nutrient taxes on fat, salt, and sugar. We find that a 20% nutrient tax has a significantly larger impact on nutrition than an equivalent product tax, due to the fact that these are broader-based taxes. However, the costs of these taxes in terms of consumer utility are only about 70 cents per household per day. A sugar tax in particular is a powerful tool to induce healthier nutritive bundles among consumers.

3D printed fluidics with embedded analytic functionality for automated reaction optimisation.

Additive manufacturing or '3D printing' is being developed as a novel manufacturing process for the production of bespoke micro- and milliscale fluidic devices. When coupled with online monitoring and optimisation software, this offers an advanced, customised method for performing automated chemical synthesis. This paper reports the use of two additive manufacturing processes, stereolithography and selective laser melting, to create multifunctional fluidic devices with embedded reaction monitoring capability. The selectively laser melted parts are the first published examples of multifunctional 3D printed metal fluidic devices. These devices allow high temperature and pressure chemistry to be performed in solvent systems destructive to the majority of devices manufactured via stereolithography, polymer jetting and fused deposition modelling processes previously utilised for this application. These devices were integrated with commercially available flow chemistry, chromatographic and spectroscopic analysis equipment, allowing automated online and inline optimisation of the reaction medium. This set-up allowed the optimisation of two reactions, a ketone functional group interconversion and a fused polycyclic heterocycle formation, via spectroscopic and chromatographic analysis.

Economic preferences and fast food consumption in US adults: Insights from behavioral economics.

OBJECTIVE: To examine the relationship between economic time preferences and frequency of fast food and full-service restaurant consumption among U.S. adults. METHODS: Participants included 5871U.S. adults who responded to a survey conducted in 2011 pertaining to the lifestyle behaviors of families and the social context of these behaviors. The primary independent variable was a measure of time preferences, an intertemporal choice assessing delay discounting. This was elicited via responses to preferences for an immediate dollar amount or a larger sum in 30 (30-day time horizon) or 60days (60-day time horizon). Outcomes were the frequency of fast food and full-service restaurant consumption. Ordered logistic regression was performed to examine the relationship between time preferences and food consumption while adjusting for covariates (e.g. socio-demographics). RESULTS: Multivariable analysis revealed that higher future time preferences were significantly related to less frequent fast food intake for both the 30- and 60-day time horizon variables (P for linear trend <0.05; both). Notably, participants with the highest future time preference were significantly less likely to consume fast food than those with very low future time preferences (30-day: OR=0.74, 95%CI: 0.62-0.89; and 60-day: OR=0.86, 95%CI: 0.74-1.00). In comparison, higher future time preferences were not significantly associated with full-service restaurant intake (30-day: p for linear trend=0.73; 60-day: p for linear trend=0.83). CONCLUSIONS: Higher future time preferences were related to a lower frequency of fast food consumption. Utilizing concepts from behavioral economics (e.g. pre-commitment contracts) to facilitate more healthful eating is warranted using experimental studies.

Within-family obesity associations: evaluation of parent, child, and sibling relationships.

BACKGROUND: How parent and sibling obesity status comparatively shape a child's obesity is unknown. PURPOSE: To investigate how the obesity status of different children within the same family is related to a parent or sibling's obesity. METHODS: A national sample of adults in 10,244 American households was surveyed during 2011; data were analyzed in 2012-2013. Of these households, 1,948 adults had one or two children; provided sociodemographic information; and reported on adult and child height and weight, physical activity, and food environment. Logistic regression models were estimated in which the outcome of interest was child obesity status, with parent and sibling obesity as key predictors, adjusting for a range of both adult and child social and demographic confounders. RESULTS: In one-child households, it was 2.2 times more likely (SE=0.5) that the child would be obese if a parent was obese. In households with two children, having an obese younger sibling was more strongly associated with elder-child obesity (OR=5.4, SE=1.9) than parent's obesity status (OR=2.3, SE=0.8). Having an obese elder sibling was associated with younger-child obesity (OR=5.6, SE=1.9), and parent obesity status was no longer significant. Within-family sibling obesity was more strongly patterned between siblings of the same gender than between different genders, and child physical activity was significantly associated with obesity status. CONCLUSIONS: Considering offspring composition and sibling gender may be beneficial in childhood obesity prevention and intervention.

Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders.

UNLABELLED: Merimepodib (MMPD) is an orally administered, inosine monophosphate dehydrogenase inhibitor that has shown antiviral activity in nonresponders with chronic hepatitis C (CHC) when combined with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) and ribavirin (RBV). We conducted a randomized, double-blind, multicenter, phase 2b study to evaluate the antiviral activity, safety, and tolerability of MMPD in combination with Peg-IFN-alfa-2a and RBV in patients with genotype 1 CHC who were nonresponders to prior therapy with Peg-IFN and RBV. Patients received 50 mg MMPD, 100 mg MMPD, or placebo every 12 hours, in addition to Peg-IFN-alfa-2a and RBV, for 24 weeks. Patients with a 2-log or more decrease from baseline or undetectable hepatitis C virus (HCV) RNA levels at week 24 were then eligible to continue Peg-IFN-alfa-2a and RBV for a further 24 weeks, followed by 24 weeks of follow-up. The primary efficacy endpoint was sustained virological response (SVR) rate at week 72 in all randomized patients who received at least one dose of study drug and had a history of nonresponse to standard therapy. A total of 354 patients were randomized to treatment (117 to placebo; 119 to 50 mg MMPD; 118 to 100 mg MMPD), and 286 completed the core study. The proportion of patients who achieved SVR was similar among the treatment groups: 6% (6/107) for 50 mg MMPD, 4% (5/112) for 100 mg MMPD, and 5% (5/104) for placebo (P = 0.8431). Adverse-event profiles for the MMPD combination groups were similar to that for Peg-IFN-alfa and RBV alone. Nausea, arthralgia, cough, dyspnea, neutropenia, and anemia were more common in patients taking MMPD. CONCLUSION: The addition of MMPD to Peg-IFN-alfa-2a and RBV combination therapy did not increase the proportion of nonresponder patients with genotype 1 CHC achieving an SVR.

A phase I dose-ranging study of the pharmacokinetics, pharmacodynamics, safety, and tolerability of AVN944, an IMPDH inhibitor, in healthy male volunteers.

A phase I study of AVN944, an inosine monophosphate dehydrogenase (IMPDH) inhibitor, was carried out to assess its safety, tolerability, pharmacokinetics, and pharmacodynamics. Healthy male volunteers (N = 25) participated in this double-blind, randomized, placebo-controlled trial. Sixteen received oral doses ranging from 25 to 250 mg on 3 separate occasions at intervals of 3 or 6 days after overnight fasting. Six participants received two 100-mg doses, and 2 participants received 2 placebo doses, one with food and the other after fasting overnight. Clinical and laboratory parameters, including excretion of AVN944 and thiocyanate and IMPDH inhibition, were made at intervals for 48 hours postdosing. There were 13 mild and 2 moderate but no serious adverse events. One mild and 1 moderate event could be treatment related. AVN944 disappeared rapidly from plasma, but clearance decreased at doses > 50 mg. Food reduced absorption, with a geometric mean Cmax ratio of 33% and a geometric mean AUC0-infinity ratio of 44%. Urinary excretion was negligible. AVN944 doses > 100 mg showed definite IMPDH inhibition lasting at least 4 to 6 hours. AVN944, when administered orally to healthy volunteers, is well tolerated, absorbs better with fasting, and exhibits a pharmacodynamic profile that suggests potential for significant anticancer activity.

A phase II study of the safety and efficacy of the multidrug resistance inhibitor VX-710 combined with doxorubicin and vincristine in patients with recurrent small cell lung cancer.

BACKGROUND: Tumors with multidrug resistance (MDR) frequently up-regulate efflux proteins, including MDR-associated protein (MRP-1) and P-glycoprotein (Pgp). MDR represents an obstacle to successful chemotherapy treatment and is reversible in Pgp- or MRP-1-expressing cells by the inhibitor VX-710. A Phase II study was designed to evaluate VX-710 in combination with doxorubicin and vincristine in patients with sensitive, recurrent small cell lung cancer (SCLC). METHODS: Eligible patients had recurrent SCLC after a response to first-line chemotherapy. Stage 1 safety evaluation was completed with planned expansion if 9 responses were confirmed in the first 35 patients. Patients were treated every 21 days until progression or intolerable adverse events (AEs). RESULTS: Thirty-six patients were enrolled from 1998 to 2000. Neutropenia was the major toxicity, occurring in 26 of 36 patients (72%). Neutropenia was more severe (30% vs 20% grade 4) and developed earlier (58% vs 38% in Cycle 1) among the 15 patients who were enrolled prior to an amendment that required neutropenia prophylaxis. Four patients died on study: 2 from infections likely related to therapy and 2 from cancer progression. Seven of 36 patients (19%) had partial responses; 6 patients sustained responses through 6 cycles of treatment, with 1 response lasting 3 years. Three additional patients had unconfirmed responses, and 4 patients had stable disease. The median survival was 6 months. No correlative (99m)Tc-sestamibi uptake in tumor tissue was observed with the addition of VX-710 in this study. CONCLUSIONS: The addition of VX-710 to doxorubicin and vincristine therapy did not significantly enhance antitumor activity or survival. Although there were durable responses, criteria were not met to proceed with Stage 2 expansion.

The Aurora kinase inhibitor VX-680 induces endoreduplication and apoptosis preferentially in cells with compromised p53-dependent postmitotic checkpoint function.

VX-680 is a potent inhibitor of Aurora kinases that induces the accumulation of cells with > or =4N DNA content, followed by cell death. Here, we define the role of p53 and p21(Waf1/Cip1) in cell cycle perturbations following exposure to VX-680. Endoreduplication and apoptosis in response to VX-680 are limited in A549 and MCF-7 cells expressing wild-type p53, and markedly enhanced in cells lacking p53, including those engineered to express the HPV16-E6 oncoprotein or short interfering RNA pools targeting p53. In contrast, endoreduplication and apoptosis occur in the p53 wild-type cell lines, RKO and U2OS. The difference in response to VX-680 among these cell lines correlates with the timing of induction of p21(Waf1/Cip1) and its ability to inhibit cyclin E-cdk2 activity. In A549 cells, VX-680 induces the expression of p53 and p21(Waf1/Cip1) within 24 hours, with consequent inhibition of cyclin E-cdk2, and reduction of retinoblastoma protein phosphorylation, limiting endoreduplication. In RKO and U2OS cells, the induction of p21(Waf1/Cip1) is delayed and associated with higher residual cyclin E-cdk2 kinase activity and retinoblastoma protein phosphorylation, followed by progressive endoreduplication and apoptosis. Abrogation of p21(Waf1/Cip1) expression by short interfering RNA targeting in A549 cells results in a substantial increase in the degree of endoreduplication, whereas inducible expression of p21(Waf1/Cip1) in p53-negative NCI-H1299 cells inhibits VX-680-induced endoreduplication and cell death. These data suggest that the integrity of the p53-p21(Waf1/Cip1)-dependent postmitotic checkpoint governs the response to Aurora kinase inhibition. Although cells with intact checkpoint function arrest with 4N DNA content, those with compromised checkpoint function are more likely to undergo endoreduplication followed by eventual apoptosis.

When do false memories cross language boundaries in English-Spanish bilinguals?

To determine whether false memories cross language boundaries, we presented English-Spanish bilinguals with conceptually related word lists for five study-test trials. Some lists were heard in English, some in Spanish, and they were then followed by a recognition memory test composed of studied words, conceptually related nonstudied critical words, and unrelated words presented in the same language used at study or in a different language. Even though participants were instructed to recognize only previously heard words, they falsely recognized both same-language and different-language critical words. With practice, participants increased their accurate recognition of list words and decreased their false recognition of critical words when the study-test language was the same, and they decreased their false recognition of list words and critical words when the language differed. False memories can cross language boundaries when participants rely on conceptual representations from the word lists, but these errors decrease over trials as participants increasingly rely on language-specific lexical representations.