How Blackouts during Heat Waves Amplify Mortality and Morbidity Risk.

The recent concurrence of electrical grid failure events in time with extreme temperatures is compounding the population health risks of extreme weather episodes. Here, we combine simulated heat exposure data during historical heat wave events in three large U.S. cities to assess the degree to which heat-related mortality and morbidity change in response to a concurrent electrical grid failure event. We develop a novel approach to estimating individually experienced temperature to approximate how personal-level heat exposure changes on an hourly basis, accounting for both outdoor and building-interior exposures. We find the concurrence of a multiday blackout event with heat wave conditions to more than double the estimated rate of heat-related mortality across all three cities, and to require medical attention for between 3% (Atlanta) and more than 50% (Phoenix) of the total urban population in present and future time periods. Our results highlight the need for enhanced electrical grid resilience and support a more spatially expansive use of tree canopy and high albedo roofing materials to lessen heat exposures during compound climate and infrastructure failure events.

Safety of subcutaneous immunotherapy in patients with severe asthma.

BACKGROUND: Severe asthma (SA) has been identified as a risk factor for severe systemic reactions (SR) to allergen subcutaneous immunotherapy (SCIT). However, the incidence and characterization of SRs in SA in comparison to less severe or no asthma is not known. OBJECTIVE: The objective of this study was to characterize the incidence of SRs in patients with SA receiving SCIT in comparison to patients with no asthma or less SA. METHODS: A retrospective cohort study was performed on patients receiving SCIT from a multicenter national network of private allergy practices between January 2015 and December 2019. Demographics, asthma severity (International Classification of Diseases-10 codes), concomitant medications, aeroallergen skin testing, measures of asthma control with the asthma control test and forced expiratory volume in 1 second values, SCIT prescription, and an SR standardized form were assessed. RESULTS: A total of 65,855 patients, with 1072 patients having SA receiving SCIT, were included with a total of 4415 SRs (19.9 SR per 10,000 injection visits). Severe asthma had 23.9 SRs per 10,000 injection visits (incidence rate, 0.239; 95% confidence interval [0.189-0.298]). There were 155 grade III or IV SRs; 5 (3.2%) occurred in the SA group. There was no difference in rates of grade III or IV SRs between SA and no asthma and in rates of total SRs between SA and less SA. CONCLUSION: In a large cohort of patients with SA undergoing multiallergen SCIT drawn from a diverse outpatient allergy population, the diagnosis of SA was not associated with increased moderate-severe SRs compared with patients without asthma and any severity of asthma.

Compound Climate and Infrastructure Events: How Electrical Grid Failure Alters Heat Wave Risk.

The potential for critical infrastructure failures during extreme weather events is rising. Major electrical grid failure or "blackout" events in the United States, those with a duration of at least 1 h and impacting 50,000 or more utility customers, increased by more than 60% over the most recent 5 year reporting period. When such blackout events coincide in time with heat wave conditions, population exposures to extreme heat both outside and within buildings can reach dangerously high levels as mechanical air conditioning systems become inoperable. Here, we combine the Weather Research and Forecasting regional climate model with an advanced building energy model to simulate building-interior temperatures in response to concurrent heat wave and blackout conditions for more than 2.8 million residents across Atlanta, Georgia; Detroit, Michigan; and Phoenix, Arizona. Study results find simulated compound heat wave and grid failure events of recent intensity and duration to expose between 68 and 100% of the urban population to an elevated risk of heat exhaustion and/or heat stroke.

Real-world mapping of allergy immunotherapy in the United States: The argument for improving adherence.

Background: There is a dearth of real-world evidence studies focused on allergy immunotherapy (AIT) use among patients with allergic rhinitis (AR). Objective: This study examined claims data of AR patients residing in the United States to assess patient characteristics and health outcomes. Methods: AR patients were identified in the IBM MarketScan database between January 1, 2014, and March 31, 2017. Patients receiving AIT were identified with relevant billing codes (earliest AIT claim for vaccine as the index date); patients without AIT were identified with claims that contained a diagnosis code for AR (earliest AR claim as the index date). All the patients were required to have continuous enrollment 12 months prior to and following their index date. AIT patients reaching 25+ injection claims were analyzed as a separate maintenance cohort. Patients were assessed for demographic characteristics, comorbid conditions, and health care utilization. Results: A total of 2,334,530 AR patients were included; 103,207 had at least one AIT claim, with 45,279 (43.9%) of these patients reaching maintenance. Patients who reached AIT maintenance presented higher rates of baseline comorbidities than both the full AIT cohort and the patients with no AIT claims, including asthma (34.6% versus 30.1% versus 7.5%) and upper respiratory tract infections (63.1% versus 60.3% versus 34.2%). From baseline to follow-up, maintenance AIT patients demonstrated reductions in all AR-related comorbidities assessed, along with reductions in all-cause and AR-related service utilization. Conclusion: Patients initiating AIT presented the greatest need for therapeutic intervention, as evidenced by higher allergy-related comorbidities; those who reached maintenance demonstrated improved outcomes following the initiation of therapy. Continued efforts to increase patient awareness and adherence to AIT are needed.

A Premature Infant With Neonatal Actinomyces odontolyticus Sepsis.

We describe the presentation, diagnosis and management of a premature newborn with Actinomyces odontolyticus bacteremia; this is the first case report of neonatal sepsis secondary to this bacteria. Maternal dental infection was the likely source of the pathogen. The outcome was favorable, with good response to antimicrobial therapy with ampicillin/amoxicillin.

Heat-Related Illness Is Associated with Lack of Air Conditioning and Pre-Existing Health Problems in Detroit, Michigan, USA: A Community-Based Participatory Co-Analysis of Survey Data.

The objective of the study was to investigate, using academic-community epidemiologic co-analysis, the odds of reported heat-related illness for people with (1) central air conditioning (AC) or window unit AC versus no AC, and (2) fair/poor vs. good/excellent reported health. From 2016 to 2017, 101 Detroit residents were surveyed once regarding extreme heat, housing and neighborhood features, and heat-related illness in the prior 5 years. Academic partners selected initial confounders and, after instruction on directed acyclic graphs, community partners proposed alternate directed acyclic graphs with additional confounders. Heat-related illness was regressed on AC type or health and co-selected confounders. The study found that heat-related illness was associated with no-AC (n = 96, odds ratio (OR) = 4.66, 95% confidence interval (CI) = 1.22, 17.72); living ≤5 years in present home (n = 57, OR = 10.39, 95% CI = 1.13, 95.88); and fair/poor vs. good/excellent health (n = 97, OR = 3.15, 95% CI = 1.33, 7.48). Co-analysis suggested multiple built-environment confounders. We conclude that Detroit residents with poorer health and no AC are at greater risk during extreme heat. Academic-community co-analysis using directed acyclic graphs enhances research on community-specific social and health vulnerabilities by identifying key confounders and future research directions for rigorous and impactful research.

Reducing Vancomycin Use in a Level IV NICU.

BACKGROUND AND OBJECTIVES: Vancomycin remains one of the most commonly prescribed antibiotics in NICUs despite recommendations to limit its use for known resistant infections. Baseline data revealing substantially higher vancomycin use in our NICU compared to peer institutions informed our quality improvement initiative. Our aim was to reduce the vancomycin prescribing rate in neonates hospitalized in our NICU by 50% within 1 year and sustain for 1 year. METHODS: In the 60-bed level IV NICU of an academic referral center, we used a quality improvement framework to develop key drivers and interventions including (1) physician education with benchmarking antibiotic prescribing rates; (2) pharmacy-initiated 48-hour antibiotic time-outs on rounds; (3) development of clinical pathways to standardize empirical antibiotic choices for early-onset sepsis, late-onset sepsis, and necrotizing enterocolitis; coupled with (4) daily prospective audit with feedback from the antimicrobial stewardship program. RESULTS: We used statistical process u-charts to show vancomycin use declined from 112 to 38 days of therapy per 1000 patient-days. After education, pharmacy-initiated 48-hour time-outs, and development of clinical pathways, vancomycin use declined by 29%, and by an additional 52% after implementation of prospective audit with feedback. Vancomycin-associated acute kidney injury also declined from 1.4 to 0.1 events per 1000 patient-days. CONCLUSIONS: Through a sequential implementation approach of education, standardization of care with clinical pathways, pharmacist-initiated 48-hour time-outs, and prospective audit with feedback, vancomycin days of therapy declined by 66% over a 1-year period and has been sustained for 1 year.

Physical Activity in the Summer Heat: How Hot Weather Moderates the Relationship Between Built Environment Features and Outdoor Physical Activity of Adults.

BACKGROUND: Research has not yet examined how hot weather moderates the relationship between the built environment and outdoor physical activity levels. The authors posited that hot days will increase the magnitude of the expected directional effect of built environment features on physical activity. METHODS: This longitudinal study included 134 US adults from the Three city Heat and Electrical failure AdapTation study. Adults self-reported physical activity for multiple summer days (nstudy-days = 742) in 2016. Hot days were defined as ≥90th percentile of daily maximum heat index. Built environment features included density, safety, trees, hilliness, connectivity, access to parks, and access to shops + services. Separate growth curve models with interaction terms (ie, hot day × built environment feature) were run for daily minutes of outdoor physical activity (ie, any activity and recommended activity). RESULTS: Neither hot days nor built environment features impacted outdoor physical activity significantly, and hot days did not moderate the relationship between built environment features and physical activity (P > .05). CONCLUSIONS: With adults failing to modify behavior on hot days, cities may be placing adults at increased risk of exertional heat illness. The authors recommend incorporating the risk of exertional heat illness in health impact assessments and deploying heat management strategies.

Retrospective Study on the Association of Biomarkers With Real-world Outcomes of Omalizumab-treated Patients With Allergic Asthma.

PURPOSE: Biomarkers, including blood eosinophils (EoS) and fractional exhaled nitric oxide (FeNO), may affect omalizumab outcomes in allergic asthma, but evidence in the literature remains mixed. This study assessed omalizumab outcomes in real-world patients with allergic asthma stratified by pretreatment biomarker levels. METHODS: Patients with allergic asthma aged ≥12 years initiated on omalizumab with ≥12 months of data after index were identified in the Allergy Partners electronic medical records (2007-2018). Patients with ≥1 diagnosis of chronic obstructive pulmonary disease in combination with ≥10 pack-years of smoking, cystic fibrosis, Alpha-1 antitrypsin deficiency, bronchiectasis, interstitial lung disease, and sarcoidosis in the 12 months before or after index were excluded. Patients were stratified by pretreatment EoS (≥/<300 cells/µL) and FeNO (≥/<25 parts per billion). Outcomes, including Asthma Control Test (ACT) scores, forced expiratory volume in 1 second (FEV1), and FEV1 as a percentage of predicted value (FEV1% predicted), were compared using generalized estimating equations at 6 and 12 months after versus before index date in stratified patients with outcome measures available at both time periods. FINDINGS: A total of 77 and 86 patients were stratified into the high and low EoS strata, respectively, and 56 patients into each of the intermediate-high and low FeNO strata. Compared with 6 months before index, mean difference (MD) in ACT scores at 6 months after index reached the minimally important difference of ≥3 points in high (MD = 3.75; 95% CI, 2.05-5.45) and low (MD = 4.56; 95% CI, 2.86-6.26) EoS, as well in the intermediate-high (MD = 3.75; 95% CI, 1.95-5.55) and low (MD = 3.55; 95% CI, 1.53-5.57) FeNO strata. Statistically significant improvements in mean FEV1 were observed in the high EoS (MD = 0.22 L/s; 95% CI, 0.08-0.35 L/s) and intermediate-high FeNO (MD = 0.13 L/s; 95% CI, 0.03-0.24 L/s) strata but not in the lower strata. In terms of mean FEV1% predicted, a statistically significant improvement was observed in high EoS stratum (MD = 4.95%; 95% CI, 0.60%-9.30%). Results that compared 12 months after versus before index date were similar. IMPLICATIONS: Omalizumab was associated with statistically significant improvements in ACT scores largely reaching or exceeding minimally important difference across biomarker levels and with a statistically significant improvement in lung function more evident in high biomarker strata. Although response varied by biomarkers for some outcomes, all strata indicated improvements on ≥1 measure. Real-world patients with allergic asthma could benefit from omalizumab regardless of pretreatment biomarker levels, suggesting that pretreatment biomarker levels might not inform response.

Patient and physician preferences for attributes of biologic medications for severe asthma.

OBJECTIVE: Despite the increased availability of biologic treatments indicated for severe asthma, patient and physician preferences for these medications remains largely unknown. The purpose of this study was to understand perceptions of biologic therapies, barriers to care with biologic medications, and preferences for biologic therapy attributes. METHODS: This mixed-methods study involved quantitative surveys and qualitative telephone interviews with patients and physicians from the United States. Participants described preferences for relevant attributes, and barriers to use of biologic medications. Participants rated, ranked, and indicated importance of preferences for different levels of key attributes including: mode of administration, administration setting, dosing frequency, number of injections, and time to onset of effect. Other attributes unique to each group were also included. RESULTS: A total of 47 patients and 25 physicians participated. Patients ranked out-of-pocket costs, mode of administration, time to onset of efficacy, and administration setting as the most important attributes. Physicians ranked mode of administration, time to onset of efficacy, dosing frequency, and insurance reimbursement/access as most important. Both groups expressed preferences for less frequent administrations (Q8W over Q4W or Q2W) (all P<0.01) and subcutaneous (SC) over intravenous injection (both P<0.0001). Key patient barriers to biologic medications include location of treatment, administration time, scheduling, cost/insurance coverage, number of injections, and mode of administration. Physicians identified patient candidacy, convincing patients, administration setting, mode of administration, cost, and administrative burden as key barriers to initiating therapy; and efficacy, speed of onset, convenience of administration, cost, and patient compliance as barriers to staying on therapy. CONCLUSIONS: Patients and physicians expressed strong preferences for less frequent dosing, SC administration, and faster onset. Cost/insurance coverage and convenience issues were key barriers to use. Increased awareness and understanding of preferences and barriers may be useful in facilitating physician-patient conversations with the goal of individualizing treatment.

Long-term omalizumab outcomes in chronic idiopathic urticaria: a real-world study.

Background: Although clinical trials documented omalizumab's efficacy in U.S. patients with chronic idiopathic urticaria (CIU), the real-world evidence on its long-term effectiveness is lacking. Objective: To assess omalizumab use and the long-term response in a large sample of U.S. real-world patients. Methods: Patients with CIU and ≥ 12 years old who were initiated on omalizumab (index date) and with ≥ 6 months of postindex data were identified in an electronic medical record system (2007-2018). Omalizumab use was described. Provider assessments of disease control and course, and patient-reported symptoms were compared at 6-month intervals postindex versus baseline in the patients with values available at both time points. Results: A total of 1096 patients (mean age, 44.1 years; 74.7% women) were followed up for a mean of 19 months postindex. Patients, predominantly initiated on a 300-mg dose, received a mean of 15 omalizumab administrations and were treated continuously for a mean of 14.2 months. At 6 months postindex versus baseline, the patients (n = 708) were more likely to be well controlled (odds ratio [OR] 31.68 [95% confidence interval {CI}, 17.20-58.36]) with an improved disease course (OR 15.73 [95% CI, 11.33-21.85]). Moreover, the patients (n = 373) were less likely to report itching (OR 0.39 [95% CI, 0.21-0.76]), rash (OR 0.59 [95% CI, 0.45-0.78]), and swelling (OR 0.46 [95% CI, 0.36-0.59]). Benefits associated with omalizumab treatment were sustained through month 24 and beyond. Conclusion: This real-world study showed that the patients who received a mean of 15 omalizumab administrations over a mean of 14.2 months experienced, starting at 6 and through 24 months after omalizumab initiation and beyond, improved CIU control, course, and symptoms.

How race, ethnicity, and income moderate the relationship between urban vegetation and physical activity in the United States.

To facilitate physical activity interventions, researchers identify which factors associate with physical activity, such as vegetation levels of the surrounding environment. While most studies examining vegetation and physical activity find a positive correlation, the literature does not investigate how vegetation may have a varied effect on physical activity based on demographic composition. This study examined how race, ethnicity, and income moderate the relationship between both non-tree vegetation and tree canopy on the percentage of individuals participating in leisure-time physical activity per census tract. Physical activity data from 2013 to 2014 for 7842 census tracts across 25 US cities originated from the CDC's 500 Cities project. Aerial images from the USDA's National Agriculture Imagery Program were used to classify vegetation levels per tract. Demographic variables originated from the American Community Survey 2011-2015 5-year estimates. Tracts were stratified into four types (Black + low income, Hispanic + low income, White + high income, and remaining) and assessed through multilevel modeling as to whether tract type moderated the relationship between vegetation and physical activity. Results showed that non-tree vegetation negatively associated with physical activity across all census tract types, while tree canopy exhibited a mixed association with physical activity, based on tract type. These findings can spur further research into how vegetation impacts physical activity of different demographic groups, and potentially inform greenspace and tree planting installments in those areas at greatest risk for physical inactivity-related diseases.

Description of Baseline Characteristics of Pediatric Allergic Asthma Patients Including those Initiated on Omalizumab.

BACKGROUND: Indication of omalizumab in the United States was recently extended to include pediatric (6-11 years) uncontrolled moderate-to-severe allergic asthma patients. OBJECTIVE: The purpose of this study was to describe baseline characteristics of this population from a real-world dataset. METHODS: Allergic asthma patients and uncontrolled moderate-to-severe allergic asthma patients, aged 6-11 years, were identified in the Allergy Partners Network Electronic Medical Records (2007-2016). The index date for allergic asthma patients was the latest between the second asthma-related visit and the allergic status confirmation. Uncontrolled moderate-to-severe allergic asthma patients were stratified into omalizumab-exposed (index date) or omalizumab-unexposed (index date randomly generated) groups. Characteristics were evaluated during the 12-month preindex period. RESULTS: A total of 5806 allergic asthma, 37 omalizumab-exposed, and 2620 omalizumab-unexposed patients were selected (mean age approximately 9 years). Allergic asthma and omalizumab-unexposed patients were predominantly white (70.2% and 61.2%) whereas the majority of omalizumab-exposed were African Americans (62.2%). Mean immunoglobulin E was 782.0 IU/ml in allergic asthma patients (available in 2.2%), 1134.4 IU/ml in omalizumab-exposed (available in 100.0%), and 746.1 IU/ml in omalizumab-unexposed (available in 3.1%). Allergic asthma patients were less severe than omalizumab-exposed and omalizumab-unexposed based on the forced expiratory volume in 1 s as a percentage of predicted value (FEV1% predicted) and the Childhood Asthma Control Test (C-ACT). FEV1% predicted was below normal (<80%) in 42.4% of omalizumab-exposed and 39.1% of omalizumab-unexposed patients, also 63.6% of omalizumab-exposed and 46.7% of omalizumab-unexposed had uncontrolled asthma (C-ACT score <20). In African American omalizumab-exposed patients, FEV1% predicted was below normal in 47.6% and 55.0% had uncontrolled asthma. CONCLUSIONS: In a real-world setting, pediatric patients with uncontrolled moderate-to-severe allergic asthma have a significant disease burden as shown by high rates of poor lung function, disease control, and symptoms. Currently available treatments could help improve disease management in this population.

Characterizing patients with asthma who received Global Initiative for Asthma steps 4-5 therapy and managed in a specialty care setting.

BACKGROUND: Severe asthma is recognized in the European Respiratory Society/American Thoracic Society guidelines as a major unmet need in the management of asthma. OBJECTIVE: The study objective was to describe the clinical burden of Global Initiative for Asthma (GINA) steps 4-5 asthma for patients treated by specialists in the U.S. community setting. METHODS: Patients, ages ≥12 years, with asthma who received GINA step 4 or 5 treatment and were treated at a large U.S. allergy practice network between January 1, 2010, and April 30, 2016, were retrospectively identified by using electronic health records. Clinical outcomes included lung function (forced expiratory volume in one second of expiration [FEV1] and FEV1% predicted), symptom control (Asthma Control Test [ACT]), the fractional exhaled nitric oxide (FeNO) value (FeNO ≥25 ppb indicates airway inflammation), and asthma medication use. The change in outcomes from baseline to 12 and 24 months after the index date was calculated. RESULTS: Of 120,116 patients with asthma, 12,922 (10.8%) had severe asthma, 68% (n = 8751) while on step 4 therapy. The mean baseline prebronchodilation FEV1% predicted was 79.7%, and the mean baseline ACT score was 17.0. With uncontrolled asthma defined as an ACT score of ≤19 and/or an FEV1 value of <80% predicted and/or oral corticosteroid use of ≥2 bursts, 52.5% and 57.7% of patients on step 4 and step 5 therapy, respectively, had uncontrolled asthma at baseline. Of a subset of patients, 40.9% had an eosinophil count of ≥300 cells/mm3 and 44% had an FeNO concentration of ≥25 ppb. Small increases in the FEV1 value were observed from baseline to 12 months (n = 4022) and 24 months (n = 2326) postindex (0.07 and 0.04 L, respectively). CONCLUSION: A considerable proportion of patients had uncontrolled asthma while on current GINA steps 4-5 treatment, which indicated that additional therapies may be required to reduce the clinical burden of severe asthma.

Asthma control, lung function, symptoms, and corticosteroid sparing after omalizumab initiation in patients with allergic asthma.

BACKGROUND: Omalizumab is approved in patients with moderate-to-severe allergic asthma with symptoms uncontrolled, despite the mainstay therapy. OBJECTIVE: Electronic medical records (EMR) were used to increase the knowledge of omalizumab effectiveness in a real-world setting. METHODS: Patients with uncontrolled moderate-to-severe allergic asthma, ages ≥12 years old, initiated on omalizumab (index date), with ≥12 months of pre- and postindex data, were identified in an EMR data base. An Asthma Control Test score (≥20 is considered well controlled), forced expiratory volume in 1 second as a percentage of the predicted value (<80% considered below normal), symptoms, and oral corticosteroid (OCS) and inhaled corticosteroid (ICS) use were compared in the 12-month post- versus the preindex period with univariate generalized estimating equations adjusted for repeated measurements. RESULTS: A total of 208 patients (mean ± standard deviation[SD] age, 41 ± 19 years; 64.9% women; 71.2% white; and with a mean ± SD serum total immunoglobulin E level of 455.4 ± 644.7 IU/mL) were identified. In the post- versus preindex period, the patients were significantly more likely to have well-controlled asthma (odds ratio [OR] 1.72 [95% confidence interval {CI}, 1.11-2.64]) and less likely to have a lung function value below normal (nonsignificant) after omalizumab initiation. The patients experienced significantly less coughing (OR 0.66 [95% CI, 0.49-0.91]), shortness of breath (OR 0.60 [95% CI, 0.44-0.83]), and wheezing (OR 0.59 [95% CI, 0.43-0.81]), with no improvement in chest tightness. A significantly lower likelihood of new OCS prescriptions (OR 0.58 [95% CI, 0.41-0.82]) was observed. A lower likelihood of new high- and medium-dose ICS prescriptions was nonsignificant. CONCLUSION: Omalizumab was associated with beneficial effects on asthma control and symptoms, and the likelihood of requiring new OCS prescriptions. An observed trend of improved lung function and lower likelihood of requiring high- and medium-dose ICS did not reach statistical significance.

Multisensory Tracking of Objects in Darkness: Capture of Positive Afterimages by the Tactile and Proprioceptive Senses.

This paper reports on three experiments investigating the contribution of different sensory modalities to the tracking of objects moved in total darkness. Participants sitting in the dark were exposed to a brief, bright flash which reliably induced a positive visual afterimage of the scene so illuminated. If the participants subsequently move their hand in the darkness, the visual afterimage of that hand fades or disappears; this is presumably due to conflict between the illusory visual afterimage (of the hand in its original location) and other information (e.g., proprioceptive) from a general mechanism for tracking body parts. This afterimage disappearance effect also occurs for held objects which are moved in the dark, and some have argued that this represents a case of body schema extension, i.e. the rapid incorporation of held external objects into the body schema. We demonstrate that the phenomenon is not limited to held objects and occurs in conditions where incorporation into the body schema is unlikely. Instead, we propose that the disappearance of afterimages of objects moved in darkness comes from a general mechanism for object tracking which integrates input from multiple sensory systems. This mechanism need not be limited to tracking body parts, and thus we need not invoke body schema extension to explain the afterimage disappearance. In this series of experiments, we test whether auditory feedback of object movement can induce afterimage disappearance, demonstrate that the disappearance effect scales with the magnitude of proprioceptive feedback, and show that tactile feedback alone is sufficient for the effect. Together, these data demonstrate that the visual percept of a positive afterimage is constructed not just from visual input of the scene when light reaches the eyes, but in conjunction with input from multiple other senses.

"Vision for Action" in Young Children Aligning Multi-Featured Objects: Development and Comparison with Nonhuman Primates.

Effective vision for action and effective management of concurrent spatial relations underlie skillful manipulation of objects, including hand tools, in humans. Children's performance in object insertion tasks (fitting tasks) provides one index of the striking changes in the development of vision for action in early life. Fitting tasks also tap children's ability to work with more than one feature of an object concurrently. We examine young children's performance on fitting tasks in two and three dimensions and compare their performance with the previously reported performance of adult individuals of two species of nonhuman primates on similar tasks. Two, three, and four year-old children routinely aligned a bar-shaped stick and a cross-shaped stick but had difficulty aligning a tomahawk-shaped stick to a matching cut-out. Two year-olds were especially challenged by the tomahawk. Three and four year-olds occasionally held the stick several inches above the surface, comparing the stick to the surface visually, while trying to align it. The findings suggest asynchronous development in the ability to use vision to achieve alignment and to work with two and three spatial features concurrently. Using vision to align objects precisely to other objects and managing more than one spatial relation between an object and a surface are already more elaborated in two year-old humans than in other primates. The human advantage in using hand tools derives in part from this fundamental difference in the relation between vision and action between humans and other primates.

The Potent Humanin Analogue (HNG) Protects Germ Cells and Leucocytes While Enhancing Chemotherapy-Induced Suppression of Cancer Metastases in Male Mice.

Humanin is a peptide that is cytoprotective against stresses in many cell types. We investigated whether a potent humanin analogue S14G-humanin (HNG) would protect against chemotherapy-induced damage to normal cells without interfering with the chemotherapy-induced suppression of cancer cells. Young adult male mice were inoculated iv with murine melanoma cells. After 1 week, cancer-bearing mice were randomized to receive either: no treatment, daily ip injection of HNG, a single ip injection of cyclophosphamide (CP), or CP+HNG and killed at the end of 3 weeks. HNG rescued the CP-induced suppression of leucocytes and protected germ cell from CP-induced apoptosis. Lung metastases were suppressed by HNG or CP alone, and further suppressed by CP+HNG treatment. Plasma IGF-1 levels were suppressed by HNG with or without CP treatment. To investigate whether HNG maintains its protective effects on spermatogonial stem cells, sperm output, and peripheral leucocytes after repeated doses of CP, normal adult male mice received: no treatment, daily sc injection of HNG, 6 ip injections of CP at 5-day intervals, and the same regimens of CP+HNG and killed at the end of 4 weeks of treatment. Cauda epididymal sperm counts were elevated by HNG and suppressed by CP. HNG rescued the CP-induced suppression of spermatogonial stem cells, sperm count and peripheral leucocytes. We conclude that HNG 1) protects CP-induced loss of male germ cells and leucocytes, 2) enhances CP-induced suppression of cancer metastases, and 3) acts as a caloric-restriction mimetic by suppressing IGF-1 levels. Our findings suggest that humanin analogues may be promising adjuvants to chemotherapy.

Avoided heat-related mortality through climate adaptation strategies in three US cities.

Heat-related mortality in US cities is expected to more than double by the mid-to-late 21st century. Rising heat exposure in cities is projected to result from: 1) climate forcings from changing global atmospheric composition; and 2) local land surface characteristics responsible for the urban heat island effect. The extent to which heat management strategies designed to lessen the urban heat island effect could offset future heat-related mortality remains unexplored in the literature. Using coupled global and regional climate models with a human health effects model, we estimate changes in the number of heat-related deaths in 2050 resulting from modifications to vegetative cover and surface albedo across three climatically and demographically diverse US metropolitan areas: Atlanta, Georgia, Philadelphia, Pennsylvania, and Phoenix, Arizona. Employing separate health impact functions for average warm season and heat wave conditions in 2050, we find combinations of vegetation and albedo enhancement to offset projected increases in heat-related mortality by 40 to 99% across the three metropolitan regions. These results demonstrate the potential for extensive land surface changes in cities to provide adaptive benefits to urban populations at risk for rising heat exposure with climate change.