Maternal early warning criteria predict postpartum severe maternal morbidity and mortality after delivery hospitalization discharge: a case-control study.

BACKGROUND: The predictors of postpartum severe maternal morbidity and mortality have not been well-described using patient-level data. OBJECTIVE: This study aimed to evaluate the application of maternal early warning criteria in the postpartum period and generate a preliminary predictive model for severe maternal morbidity and mortality occurring after delivery hospitalization discharge until 42 days postpartum. STUDY DESIGN: A retrospective case-control study was conducted from January 2013 to September 2020. Cases were identified from electronic medical records using the International Classification of Diseases, Tenth Revision codes for Centers for Disease Control and Prevention-defined severe maternal morbidity. Patients meeting the criteria for severe maternal morbidity and mortality from delivery hospitalization discharge until 42 days postpartum were matched for delivery hospital and year with the controls in an approximate 1:2 fashion. The objective was to identify the demographic and clinical risk factors during the antepartum through postpartum periods for postpartum severe maternal morbidity and mortality. Multivariable logistic regression was performed to estimate the risks, and a receiver operating characteristic curve was derived to evaluate the model. RESULTS: Ninety cases of postpartum severe maternal morbidity and mortality that occurred following delivery hospitalization discharge were identified. These were matched with 175 controls. Women with postpartum severe maternal morbidity and mortality had more postpartum assessments (mean: 1.7 vs 1.4, P=.005) and a higher frequency of maternal early warning criteria (58% [52/90] vs 2% [3/175]; P<.001) preceding the diagnosis of severe maternal morbidity and mortality than controls. Black women had higher odds of postpartum severe maternal morbidity and mortality than White women (odds ratio, 1.93; 95% confidence interval, 1.14-3.27). Women with maternal early warning criteria during postpartum assessments were more likely to experience subsequent postpartum severe maternal morbidity and mortality (odds ratio, 67.2; 95% confidence interval, 21.3-211.6) than women with no maternal early warning criteria. Although the point estimate was different in Black women (odds ratio, 161.8; 95% confidence interval, 8.9 to >999) than White women (odds ratio, 47.9; 95% confidence interval, 13.8-167.1), the effect modification between the maternal early warning criteria and race was not statistically significant (P=.93). In a multivariable model, race, body mass index, cesarean delivery, and maternal early warning criteria at postpartum assessments were associated with subsequent severe maternal morbidity and mortality, with an area under the curve of 0.905 (95% confidence interval, 0.864-0.946). CONCLUSION: Maternal early warning criteria are associated with increased odds of postpartum severe maternal morbidity and mortality. A straightforward model that includes race, body mass index, cesarean delivery, and presence of maternal early warning criteria appears to be a promising tool to identify those at risk for postpartum severe maternal morbidity and mortality following delivery hospitalization discharge. This is an important first step in improving the ability to recognize and respond to conditions preceding postpartum severe maternal morbidity. These findings should be validated in a prospective cohort.

Secreted Toxins From Staphylococcus aureus Strains Isolated From Keratinocyte Skin Cancers Mediate Pro-tumorigenic Inflammatory Responses in the Skin.

Squamous cell carcinoma (SCC) is a common type of skin cancer that typically arises from premalignant precursor lesions named actinic keratoses (AK). Chronic inflammation is a well-known promoter of skin cancer progression. AK and SCC have been associated with an overabundance of the bacterium Staphylococcus aureus (S. aureus). Certain secreted products from S. aureus are known to promote cutaneous pro-inflammatory responses; however, not all S. aureus strains produce these. As inflammation plays a key role in SCC development, we investigated the pro-inflammatory potential and toxin secretion profiles of skin-cancer associated S. aureus. Sterile culture supernatants ("secretomes") of S. aureus clinical strains isolated from AK and SCC were applied to human keratinocytes in vitro. Some S. aureus secretomes induced keratinocytes to overexpress inflammatory mediators that have been linked to skin carcinogenesis, including IL-6, IL-8, and TNFα. A large phenotypic variation between the tested clinical strains was observed. Strains that are highly pro-inflammatory in vitro also caused more pronounced skin inflammation in mice. Proteomic characterization of S. aureus secretomes using mass spectrometry established that specific S. aureus enzymes and cytolytic toxins, including hemolysins, phenol-soluble modulins, and serine proteases, as well as currently uncharacterized proteins, correlate with the pro-inflammatory S. aureus phenotype. This study is the first to describe the toxin secretion profiles of AK and SCC-associated S. aureus, and their potential to induce a pro-inflammatory environment in the skin. Further studies are needed to establish whether these S. aureus products promote SCC development by mediating chronic inflammation.

Combining DNMT and HDAC6 inhibitors increases anti-tumor immune signaling and decreases tumor burden in ovarian cancer.

Novel therapies are urgently needed for ovarian cancer, the deadliest gynecologic malignancy. Ovarian cancer has thus far been refractory to immunotherapies that stimulate the host immune system to recognize and kill cancer cells. This may be because of a suppressive tumor immune microenvironment and lack of recruitment and activation of immune cells that kill cancer cells. Our previous work showed that epigenetic drugs including DNA methyltransferase inhibitors and histone deacetylase 6 inhibitors (DNMTis and HDAC6is) individually increase immune signaling in cancer cells. We find that combining DNMTi and HDAC6i results in an amplified type I interferon response, leading to increased cytokine and chemokine expression and higher expression of the MHC I antigen presentation complex in human and mouse ovarian cancer cell lines. Treating mice bearing ID8 Trp53-/- ovarian cancer with HDAC6i/DNMTi led to an increase in tumor-killing cells such as IFNg+ CD8, NK, and NKT cells and a reversal of the immunosuppressive tumor microenvironment with a decrease in MDSCs and PD-1hi CD4 T cells, corresponding with an increase in survival. Thus combining the epigenetic modulators DNMTi and HDAC6i increases anti-tumor immune signaling from cancer cells and has beneficial effects on the ovarian tumor immune microenvironment.

Parsimonious test of dynamic interaction.

In recent years, there have been significant advances in the technology used to collect data on the movement and activity patterns of humans and animals. GPS units, which form the primary source of location data, have become cheaper, more accurate, lighter and less power-hungry, and their accuracy has been further improved with the addition of inertial measurement units. The consequence is a glut of geospatial time series data, recorded at rates that range from one position fix every several hours (to maximize system lifetime) to ten fixes per second (in high dynamic situations). Since data of this quality and volume have only recently become available, the analytical methods to extract behavioral information from raw position data are at an early stage of development. An instance of this lies in the analysis of animal movement patterns. When investigating solitary animals, the timing and location of instances of avoidance and association are important behavioral markers. In this paper, a novel analytical method to detect avoidance and association between individuals is proposed; unlike existing methods, assumptions about the shape of the territories or the nature of individual movement are not needed. Simulations demonstrate that false positives (type I error) are rare (1%-3%), which means that the test rarely suggests that there is an association if there is none.

Direct benefits and indirect costs of warm temperatures for high-elevation populations of a solitary bee.

Warm temperatures are required for insect flight. Consequently, warming could benefit many high-latitude and high-altitude insects by increasing opportunities for foraging or oviposition. However, warming can also alter species interactions, including interactions with natural enemies, making the net effect of rising temperatures on population growth rate difficult to predict. We investigated the temperature-dependence of nesting activity and lifetime reproductive output over 3 yr in subalpine populations of a pollen-specialist bee, Osmia iridis. Rates of nest provisioning increased with ambient temperatures and with availability of floral resources, as expected. However, warmer conditions did not increase lifetime reproductive output. Lifetime offspring production was best explained by rates of brood parasitism (by the wasp Sapyga), which increased with temperature. Direct observations of bee and parasite activity suggest that although activity of both species is favored by warmer temperatures, bees can be active at lower ambient temperatures, while wasps are active only at higher temperatures. Thus, direct benefits to the bees of warmer temperatures were nullified by indirect costs associated with increased parasite activity. To date, most studies of climate-change effects on pollinators have focused on changing interactions between pollinators and their floral host-plants (i.e., bottom-up processes). Our results suggest that natural enemies (i.e., top-down forces) can play a key role in pollinator population regulation and should not be overlooked in forecasts of pollinator responses to climate change.

Ridaforolimus improves the anti-tumor activity of dual HER2 blockade in uterine serous carcinoma in vivo models with HER2 gene amplification and PIK3CA mutation.

OBJECTIVE: Uterine serous carcinomas (USC) harbor simultaneous HER2 (ERBB2) over-expression and gain of function mutations in PIK3CA. These concurrent alterations may uncouple single agent anti-HER2 therapeutic efficacy making inhibition of the mammalian target of rapamycin (mTOR) a promising option to heighten anti-tumor response. METHODS: Both in vitro and in vivo experiments were conducted to assess proliferation, cell death and anti-tumor activity of ridaforolimus, lapatinib and combination lapatinib, trastuzumab (L/T) and ridaforolimus. With institutional approval, NOD/SCID mice bearing xenografts of non-immortalized, HER2 gene amplified cell lines (ARK1, ARK2) with and without PIK3CA gene mutations were divided into four arm cohorts. Ridaforolimus was administered alone and in combination with L/T. Tumor volumes were assessed and posttreatment analysis was performed. RESULTS: We observed dose dependent in vitro abrogation of downstream target proteins including phospho-AKT and phospho-S6. In both in vivo models, single agent ridaforolimus impaired xenograft tumor growth. Combination ridaforolimus and L/T, however, further improved the observed anti-tumor activity only in the ARK1 model with the PIK3CA gene mutation (E542K). The addition of mTOR inhibition to dual HER2 blockade added no additional anti-tumor effects in the ARK2 xenografts. Western blot and immunohistochemical analysis of downstream pathway alterations following in vivo treatment revealed dual HER2 blockade with ridaforolimus was necessary to induce apoptosis, decrease proliferation and abrogate phospho-S6 protein expression in the PIK3CA mutated model. CONCLUSIONS: These pilot data suggest that PIK3CA gene mutation may be an effective biomarker for selecting those HER2 over-expressing USC tumors most likely to benefit from mTOR inhibition.

Artificial light pollution increases nocturnal vigilance in peahens.

Artificial light pollution is drastically changing the sensory environments of animals. Even though many animals are now living in these changed environments, the effect light pollution has on animal behavior is poorly understood. We investigated the effect of light pollution on nocturnal vigilance in peahens (Pavo cristatus). Captive peahens were exposed to either artificial lighting or natural lighting at night. We employed a novel method to record their vigilance behavior by attaching accelerometers to their heads and continuously monitoring their large head movements. We found that light pollution significantly increases nocturnal vigilance in peahens. Furthermore, the birds faced a trade-off between vigilance and sleep at night: peahens that were more vigilant spent less time sleeping. Given the choice, peahens preferred to roost away from high levels of artificial lighting but showed no preference for roosting without artificial lighting or with low levels of artificial lighting. Our study demonstrates that light pollution can have a substantial impact on animal behavior that can potentially result in fitness consequences.

The utility of adding expiratory or decubitus chest radiographs to the radiographic evaluation of suspected pediatric airway foreign bodies.

STUDY OBJECTIVE: This study aimed to compare test characteristics of standard (lateral and posteroanterior or anteroposterior) chest radiographs with and without special views (expiratory or bilateral decubitus) in the emergency department evaluation of children with suspected airway foreign bodies. METHODS: From 1997 to 2008, 328 patients with a suspected airway foreign body had standard and special view chest radiographs: 192 with left and right decubitus views, 133 with expiratory views, and 3 with both. Patients were excluded for cardiorespiratory disease, chest wall deformity, visible airway foreign bodies on standard views, or spontaneously expelled airway foreign bodies. After blinded radiologist review, standard plus special view test characteristics were compared to standard views. RESULTS: Nine upper airway and 70 tracheobronchial airway foreign bodies were identified by direct visualization or bronchoscopy, and the remainder were ruled out by bronchoscopy (50 patients) or clinically (199 patients). The sensitivity and specificity of the radiographs were, respectively, decubitus cohort, standard views, 56% and 79% and standard+decubitus views, 56% and 64%; expiratory radiograph cohort, standard views, 33% and 70% and standard+expiratory views, 62% and 72%. For standard plus decubitus views versus standard views alone, the relative sensitivity was 1.0 (0.56/0.56; 95% confidence interval [CI] 0.81 to 1.23) and the relative 1-specificity was 1.76 (0.36/0.21; 95% CI 1.3 to 2.37). For standard plus expiratory views versus standard views alone, the relative sensitivity was 1.87 (0.62/0.33; 95% CI 1.23 to 2.83) and the relative 1-specificity was 0.93 (0.28/0.3; 95% CI 0.6 to 1.44). CONCLUSION: The addition of decubitus to standard views increases false positives without increasing true positives and lacks clinical benefit. The addition of expiratory to standard views increases true positives without increasing false positives, but test accuracy remains low and the clinical benefit is uncertain.

What is the function of nail biting: an analog assessment study.

OBJECTIVE: To compare the frequency of nail biting in 4 settings (interventions) designed to elicit the functions of nail biting and to compare the results with a self-report questionnaire about the functions of nail biting. DESIGN: Randomised allocation of participants to order of conditions. SETTING: University Psychology Department. SUBJECTS: Forty undergraduates who reported biting their nails. INTERVENTIONS: Left alone (boredom), solving maths problems (frustration), reprimanded for nail biting (contingent attention), continuous conversation (noncontingent attention). MAIN OUTCOME MEASURES: Number of times the undergraduates bit their nails. RESULTS: Nail biting occurred most often in two conditions, boredom and frustration. CONCLUSION: Nail biting in young adults occurs as a result of boredom or working on difficult problems, which may reflect a particular emotional state. It occurs least often when people are engaged in social interaction or when they are reprimanded for the behavior.

The self-regulating nature of spontaneous synchronized activity in developing mouse cortical neurones.

Waves of spontaneous electrical activity that are highly synchronized across large populations of neurones occur throughout the developing mammalian central nervous system. The stages at which this activity occurs are tightly regulated to allow activity-dependent developmental programmes to be initiated correctly. What determines the onset and cessation of spontaneous synchronous activity (SSA) in a particular region of the nervous system, however, remains unclear. We have tested the hypothesis that activity itself triggers developmental changes in intrinsic and circuit properties that determine the stages at which SSA occurs. To do this we exposed cultured slices of mouse neocortex to tetrodotoxin (TTX) to block SSA, which normally occurs between embryonic day 17 (E17) and postnatal day 3 (P3). In control cultured slices, SSA rarely occurs after P3. In TTX-treated slices, however, SSA was generated from P3 (the day of TTX removal) until at least P10. This indicates that in the absence of spontaneous activity, the mechanisms that normally determine the timing of SSA are not initiated, and that a compensatory response occurs that shifts the time of SSA occurrence to later developmental stages.