Phosphorus-bearing molecules PO and PN at the edge of the Galaxy.

Despite its importance in planet formation and biology1, phosphorus has been identified only in the inner 12 kpc of the Galaxy2-19. The study of this element has been hindered in part by unfavourable atomic transitions2,4,20. Phosphorus is thought to be created by neutron capture on 29Si and 30Si in massive stars20,21, and released into the interstellar medium by Type II supernova explosions2,22. However, models of galactic chemical evolution must arbitrarily increase the supernovae production23 to match observed abundances. Here we present the detection of gas-phase phosphorus in the Outer Galaxy through millimetre spectra of PO and PN. Rotational lines of these molecules were observed in the dense cloud WB89-621, located 22.6 kpc from the Galactic Centre24. The abundances of PO and PN in WB89-621 are comparable to values near the Solar System25. Supernovae are not present in the Outer Galaxy26, suggesting another source of phosphorus, such as 'Galactic Fountains', where supernova material is redistributed through the halo and circumgalactic medium27. However, fountain-enriched clouds are not found at such large distances. Any extragalactic source, such as the Magellanic Clouds, is unlikely to be metal rich28. Phosphorus instead may be produced by neutron-capture processes in lower mass asymptotic giant branch stars29 which are present in the Outer Galaxy. Asymptotic giant branch stars also produce carbon21, flattening the extrapolated metallicity gradient and accounting for the high abundances of C-containing molecules in WB89-621.

Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC.

BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. PATIENTS AND METHODS: Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. RESULTS: In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. CONCLUSIONS: In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.

Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma.

BACKGROUND: The survival advantage of induction chemotherapy (IC) followed by locoregional treatment is controversial in locally advanced head and neck squamous cell carcinoma (LAHNSCC). We previously showed feasibility and safety of cetuximab-based IC (paclitaxel/carboplatin/cetuximab-PCC, and docetaxel/cisplatin/5-fluorouracil/cetuximab-C-TPF) followed by local therapy in LAHNSCC. The primary end point of this phase II clinical trial with randomization to PCC and C-TPF followed by combined local therapy in patients with LAHNSCC stratified by human papillomavirus (HPV) status and T-stage was 2-year progression-free survival (PFS) compared with historical control. PATIENTS AND METHODS: Eligible patients were ≥18 years with squamous cell carcinoma of the oropharynx, oral cavity, nasopharynx, hypopharynx, or larynx with measurable stage IV (T0-4N2b-2c/3M0) and known HPV by p16 status. Stratification was by HPV and T-stage into one of the two risk groups: (i) low-risk: HPV-positive and T0-3 or HPV-negative and T0-2; (ii) intermediate/high-risk: HPV-positive and T4 or HPV-negative and T3-4. Patient reported outcomes were carried out. RESULTS: A total of 136 patients were randomized in the study, 68 to each arm. With a median follow up of 3.2 years, the 2-year PFS in the PCC arm was 89% in the overall, 96% in the low-risk and 67% in the intermediate/high-risk groups; in the C-TPF arm 2-year PFS was 88% in the overall, 88% in the low-risk and 89% in the intermediate/high-risk groups. CONCLUSION: The observed 2-year PFS of PCC in the low-risk group and of C-TPF in the intermediate/high-risk group showed a 20% improvement compared with the historical control derived from RTOG-0129, therefore reaching the primary end point of the trial.

Parents' and healthcare professionals' experiences of care after stillbirth in low- and middle-income countries: a systematic review and meta-summary.

BACKGROUND: Stillbirth has a profound impact on women, families, and healthcare workers. The burden is highest in low- and middle-income countries (LMICs). There is need for respectful and supportive care for women, partners, and families after bereavement. OBJECTIVE: To perform a qualitative meta-summary of parents' and healthcare professionals' experiences of care after stillbirth in LMICs. SEARCH STRATEGY: Search terms were formulated by identifying all synonyms, thesaurus terms, and variations for stillbirth. Databases searched were AMED, EMBASE, MEDLINE, PsychINFO, BNI, CINAHL. SELECTION CRITERIA: Qualitative, quantitative, and mixed method studies that addressed parents' or healthcare professionals' experience of care after stillbirth in LMICs. DATA COLLECTION AND ANALYSIS: Studies were screened, and data extracted in duplicate. Data were analysed using the Sandelowski meta-summary technique that calculates frequency and intensity effect sizes (FES/IES). MAIN RESULTS: In all, 118 full texts were screened, and 34 studies from 17 countries were included. FES range was 15-68%. Most studies had IES 1.5-4.5. Women experience a broad range of manifestations of grief following stillbirth, which may not be recognised by healthcare workers or in their communities. Lack of recognition exacerbates negative experiences of stigmatisation, blame, devaluation, and loss of social status. Adequately developed health systems, with trained and supported staff, are best equipped to provide the support and information that women want after stillbirth. CONCLUSIONS: Basic interventions could have an immediate impact on the experiences of women and their families after stillbirth. Examples include public education to reduce stigma, promoting the respectful maternity care agenda, and investigating stillbirth appropriately. TWEETABLE ABSTRACT: Reducing stigma, promoting respectful care and investigating stillbirth have a positive impact after stillbirth for women and families in LMICs.

Making stillbirths visible: a systematic review of globally reported causes of stillbirth.

BACKGROUND: Stillbirth is a global health problem. The World Health Organization (WHO) application of the International Classification of Diseases for perinatal mortality (ICD-PM) aims to improve data on stillbirth to enable prevention. OBJECTIVES: To identify globally reported causes of stillbirth, classification systems, and alignment with the ICD-PM. SEARCH STRATEGY: We searched CINAHL, EMBASE, Medline, Global Health, and Pubmed from 2009 to 2016. SELECTION CRITERIA: Reports of stillbirth causes in unselective cohorts. DATA COLLECTION AND ANALYSIS: Pooled estimates of causes were derived for country representative reports. Systems and causes were assessed for alignment with the ICD-PM. Data are presented by income setting (low, middle, and high income countries; LIC, MIC, HIC). MAIN RESULTS: Eighty-five reports from 50 countries (489 089 stillbirths) were included. The most frequent categories were Unexplained, Antepartum haemorrhage, and Other (all settings); Infection and Hypoxic peripartum (LIC), and Placental (MIC, HIC). Overall report quality was low. Only one classification system fully aligned with ICD-PM. All stillbirth causes mapped to ICD-PM. In a subset from HIC, mapping obscured major causes. CONCLUSIONS: There is a paucity of quality information on causes of stillbirth globally. Improving investigation of stillbirths and standardisation of audit and classification is urgently needed and should be achievable in all well-resourced settings. Implementation of the WHO Perinatal Mortality Audit and Review guide is needed, particularly across high burden settings. FUNDING: HR, SH, SHL, and AW were supported by an NHMRC-CRE grant (APP1116640). VF was funded by an NHMRC-CDF (APP1123611). TWEETABLE ABSTRACT: Urgent need to improve data on causes of stillbirths across all settings to meet global targets. PLAIN LANGUAGE SUMMARY: Background and methods Nearly three million babies are stillborn every year. These deaths have deep and long-lasting effects on parents, healthcare providers, and the society. One of the major challenges to preventing stillbirths is the lack of information about why they happen. In this study, we collected reports on the causes of stillbirth from high-, middle-, and low-income countries to: (1) Understand the causes of stillbirth, and (2) Understand how to improve reporting of stillbirths. Findings We found 85 reports from 50 different countries. The information available from the reports was inconsistent and often of poor quality, so it was hard to get a clear picture about what are the causes of stillbirth across the world. Many different definitions of stillbirth were used. There was also wide variation in what investigations of the mother and baby were undertaken to identify the cause of stillbirth. Stillbirths in all income settings (low-, middle-, and high-income countries) were most frequently reported as Unexplained, Other, and Haemorrhage (bleeding). Unexplained and Other are not helpful in understanding why a baby was stillborn. In low-income countries, stillbirths were often attributed to Infection and Complications during labour and birth. In middle- and high-income countries, stillbirths were often reported as Placental complications. Limitations We may have missed some reports as searches were carried out in English only. The available reports were of poor quality. Implications Many countries, particularly those where the majority of stillbirths occur, do not report any information about these deaths. Where there are reports, the quality is often poor. It is important to improve the investigation and reporting of stillbirth using a standardised system so that policy makers and healthcare workers can develop effective stillbirth prevention programs. All stillbirths should be investigated and reported in line with the World Health Organization standards.

Maternal complications associated with stillbirth delivery: A cross-sectional analysis.

This study sought to identify delivery complications associated with stillbirth labour and delivery. We conducted a retrospective chart review evaluating stillbirth demographics, pregnancy and maternal risk factors, and complications of labour and delivery. We performed bivariable analysis and multivariable logistic regression to evaluate factors associated with medical complications and variations by race. Our cohort included 543 mothers with stillbirth, of which two-thirds were African-American. We noted high rates of shoulder dystocia, clinical chorioamnionitis, postpartum haemorrhage and retained placenta in women with stillbirths. Thirty-three women (6%) experienced at least one serious maternal complication. Complication rates did not vary by maternal race. Providers who perform obstetrical care should be alert to the high rate of maternal medical complications associated with labour and delivery of a stillbirth foetus.

Climate Change Effects on Pathogen Emergence: Artificial Intelligence to Translate Big Data for Mitigation.

Plant pathology has developed a wide range of concepts and tools for improving plant disease management, including models for understanding and responding to new risks from climate change. Most of these tools can be improved using new advances in artificial intelligence (AI), such as machine learning to integrate massive data sets in predictive models. There is the potential to develop automated analyses of risk that alert decision-makers, from farm managers to national plant protection organizations, to the likely need for action and provide decision support for targeting responses. We review machine-learning applications in plant pathology and synthesize ideas for the next steps to make the most of these tools in digital agriculture. Global projects, such as the proposed global surveillance system for plant disease, will be strengthened by the integration of the wide range of new data, including data from tools like remote sensors, that are used to evaluate the risk ofplant disease. There is exciting potential for the use of AI to strengthen global capacity building as well, from image analysis for disease diagnostics and associated management recommendations on farmers' phones to future training methodologies for plant pathologists that are customized in real-time for management needs in response to the current risks. International cooperation in integrating data and models will help develop the most effective responses to new challenges from climate change.

Navigating care after a baby dies: a systematic review of parent experiences with health providers.

INTRODUCTION: Health care providers are on the front lines of care when a baby dies, but there is no consensus about which behaviors are most helpful or harmful for families. MATERIALS AND METHODS: This systematic review of more than 1100 English-language articles from 1966 to 2006 addressed fetal and early infant loss and extracted information about interactions with health providers. RESULTS: Sixty-one studies, covering over 6000 parents, met criteria. Nurses were generally viewed as more emotionally supportive than physicians. Parents valued emotional support, attention to mother and baby and grief education. Avoidance, insensitivity and poor staff communication were the most distressing behaviors encountered. DISCUSSION: Interactions with health providers has profound effects on parents with perinatal losses. Grieving parents perceive many behaviors to be thoughtless or insensitive. Physicians and nurses may benefit from increased training in bereavement support.

Who tells a mother her baby has died? Communication and staff presence during stillbirth delivery and early infant death.

OBJECTIVE: Perinatal loss (stillbirth or early infant death) is often a sudden, unexpected event for families. We evaluated who communicates the loss to the parents and who is there for support at the delivery or death. STUDY DESIGN: We conducted a mail survey of 900 bereaved and 500 live-birth mothers to assess emotional, physical and reproductive health outcomes. RESULTS: We had a 44% response rate at 9 months after birth or loss from 377 bereaved mothers and 232 with surviving infants. Bereaved women were less likely to have hospital staff or family members present at delivery. African-American (versus Caucasian) mothers were half as likely to have first heard about their stillbirth from a physician or midwife. CONCLUSION: This is the first large study documenting who communicates perinatal death to families and who is present for support. Hospitals should be aware that many bereaved families may lack support at critical times.

Serendipity in diagnostic imaging: magnetic resonance imaging of the breast.

BACKGROUND: Magnetic resonance imaging (MRI) of the breast has been proposed as a noninvasive diagnostic test for evaluation of suspicious ("index") lesions noted on mammography and/or clinical breast examination (CBE). However, women may have incidental ("serendipitous") lesions detected by MRI that are not found on mammography or CBE. To understand better whether or not biopsy procedures should be performed to evaluate serendipitous lesions, we estimated the breast cancer risk for women with this type of lesion. METHODS: A decision analysis model was used to estimate the positive predictive value (i.e., the chance that a woman with a serendipitous lesion has cancer) of MRI for serendipitous lesions in women who had an abnormal mammogram and/or CBE suspicious for cancer (where a biopsy procedure is recommended). We restricted the analysis to data from women whose index lesions were noncancerous and used meta-analysis of published medical literature to determine the likelihood ratios (measures of how test results change the probability of having cancer) for MRI and the combination of CBE and mammography. The positive predictive value of MRI was calculated using the U.S. population prevalence of cancer (derived from registry data) and the likelihood ratios of the diagnostic tests. RESULTS: Under a wide variety of assumptions, the positive predictive value of MRI was extremely low for serendipitous lesions. For instance, assuming sensitivity and specificity values for MRI of 95.6% and 68.6%, respectively, approximately four of 1000 55- to 59-year-old women with serendipitous lesions would be expected to have cancer (positive predictive value = 0.44%, 95% confidence interval = 0.24%-0.67%). CONCLUSION: In women with a suspicious lesion discovered by mammography and/or CBE that is found to be benign, serendipitous breast lesions detected by MRI are extremely unlikely to represent invasive breast cancer. Immediate biopsy of such serendipitous lesions may, therefore, not be required.

Effect of pacing-induced myocardial ischemia on platelet activation and fibrin formation in the coronary circulation.

The effect of pacing-induced myocardial ischemia on platelet activation and fibrin formation was investigated in seven patients with severe proximal lesions of the left anterior descending coronary artery to determine if acute ischemia activates the coagulation system. Fibrin formation was assessed from plasma levels of fibrinopeptide A. Platelet activation was assessed by levels of platelet factor 4, beta-thromboglobulin and thromboxane B2. Plasma levels were measured before, during and after acute myocardial ischemia induced by rapid atrial pacing. Blood samples were collected from the ascending aorta and from the great cardiac vein through heparin-bonded catheters. The occurrence of anterior myocardial ischemia was established by electrocardiography and by myocardial lactate extraction. No significant transmyocardial gradients in the levels of fibrinopeptide A, platelet factor 4, beta-thromboglobulin or thromboxane B2 were found at rest, during ischemia or in the recovery period, and levels in the great cardiac vein did not change in response to ischemia. These data indicate that pacing-induced myocardial ischemia does not result in release of fibrinopeptide A, platelet factor 4, beta-thromboglobulin or thromboxane B2 into the coronary circulation, and imply that acute ischemia does not induce platelet activation or fibrin formation in the coronary circulation.

Continuity of care and the use of breast and cervical cancer screening services in a multiethnic community.

OBJECTIVE: To examine how continuity of care affects the use of breast and cervical cancer screening in a multiethnic population. METHODS: All data came from a structured telephone survey of a population-based quota sample designed to determine the cancer prevention needs of multiethnic blacks and Hispanics in New York, NY, in 1992. The study included 1420 women of 7 racial/ethnic groups: US-born blacks, English-speaking Caribbean-born blacks, Haitian blacks, and Puerto Rican, Dominican, Colombian, and Ecuadorian Hispanics. The main outcome measures were ever and recently having had a Papanicolaou smear, clinical breast examination (CBE), or mammogram. RESULTS: Among respondents who qualified for the survey on the basis of age and ethnicity, the refusal rate for completing the interview was 2.1%. Compared with women without a usual site of care, those with a usual site, but no regular clinician, were 1.56, 2.45 (P < or = .01), and 2.32 (P < or = .05) times as likely ever to have received a Papanicolaou smear, CBE, or mammogram, respectively and 1.84, 1.92 (P < or = .05), and 1.75 times as likely to have received a recent Papanicolaou smear, CBE, or mammogram, respectively. Compared with women without a usual site of care, women with a regular clinician at that usual site of care were 2.63 (P < or = .01), 2.83 (P < or = .01), and 2.30 (P < or = .05) times as likely ever to have received a Papanicolaou smear, CBE, or mammogram, and were 2.00 (P < or = .05), 2.65 (P < or = .01), and 1.40 times as likely to have recently received a Papanicolaou smear, CBE, or mammogram, respectively (adjusted odds ratios). For uninsured women, presence of a usual site of care was associated with increases in recent use of cancer screening for all screening tests. CONCLUSIONS: There is a linear trend in increasing breast and cervical cancer screening rates when one goes from having no usual source of care, to having a usual source, and to having a regular clinician at that usual source. Emphasis on continuity of care, especially on usual source of care, may help to bridge the gap in access to cancer prevention services faced by minority women.

Physician resource use and willingness to participate in assisted suicide.

OBJECTIVE: To explore the relationship between general internists' tendency to conserve medical resources and their willingness to participate in physician-assisted suicide (PAS). DESIGN AND PARTICIPANTS: Survey of a random sample of general internists in 6 urban areas of the United States. MEASUREMENTS: We assessed the physicians' use of medical resources by constructing a scale based on 6 hypothetical clinical scenarios in which respondents were given a choice between resource-intensive and resource-conserving options. We then presented a scenario of a competent terminally ill patient with breast cancer making stable and persistent requests for PAS. RESULTS: Sixty-seven (33%) of the 206 respondents indicated that they would participate in the suicide of the depicted patient. In a multivariate model, physicians who were more conservative with resources were 6.4 times more likely than their resource-intensive counterparts to prescribe the requested drugs (P = .02); minority physicians were less willing than whites to participate in PAS (odds ratio, 0.34; P = .03). Physicians' number of years in practice, location, sex, reported percentage of fee-for-service patients, and self-reported strength and direction of financial incentives in the respondents' practices were not associated with willingness to prescribe drugs for PAS. CONCLUSIONS: Most general internists, especially minority physicians, are personally reluctant to participate in PAS. While the characteristics of their practices do not affect PAS, physicians who tend to practice resource-conserving medicine are significantly more likely than their resource-intensive counterparts to provide a lethal prescription at the request of a terminally ill patient.

The psychiatric uses of cold wet sheet packs.

The cold wet sheet pack is a treatment that is seldom discussed anymore. The authors present results of a national survey which demonstrated that this treatment is rarely used in modern American psychiatry. They retrospectively review its recent use for 46 hospitalized psychiatric patients and conclude that the treatment is safe and has interesting and useful effects that go beyond the concept of simple restraint. Further study of treatment with cold wet sheet packs is recommended before it disappears altogether.

Is HIV infection a cofactor for cervical squamous cell neoplasia?

The objective of this study was to test the hypothesis that HIV interacts with human papilloma virus (HPV) to increase the odds of cervical neoplasia. The study design was a meta-analysis using data pooled from published sources. Studies published between January 1986 and March 1998 were eligible for inclusion if they included data on neoplasia (cytology-based), HIV (defined by laboratory and/or standard clinical criteria), and HPV (assessed by PCR, Southern blot, dot-blot hybridization, or cytology of an otherwise well designed study) among nonpregnant women. Blinded data abstraction was performed independently by the investigators. There were 15 studies that were eligible and presented data in a format that could be abstracted for analysis. Data were pooled using a Mantel-Haenszel summary odds ratio (OR); generalized estimation regression equations were used to examine independent effects of HIV and HPV. Overall, based on the Mantel-Haenszel ORs, there was a strong overall association between HPV and neoplasia [OR, 8.1; 95% confidence interval (CI), 6.5-10.1]. Stratifying by HIV status, HIV-positive women had higher odds of disease (OR, 8.8; 95% CI, 6.3-12.5) than HIV-negative women (OR, 5.0; 95% CI, 3.7-6.8). In the regression model, there was an interaction between HPV and HIV (P = 0.01); immunosuppression also tended to predict neoplasia (P = 0.058). HIV seems to be a cofactor in the association between HPV and cervical neoplasia; this effect may vary by level of immune function. These speculations are biologically plausible. Additional data from large, well designed studies are needed to confirm these hypotheses.

Long-term survival of patients with Wegener's granulomatosis from the American College of Rheumatology Wegener's Granulomatosis Classification Criteria Cohort.

OBJECTIVE: To determine survivorship in Wegener's granulomatosis (WG) in a well-defined multicenter cohort. METHODS: Follow-up was obtained for 77 of the 85 patients enrolled in the 1990 American College of Rheumatology vasculitis classification study. RESULTS: There were 28 deaths (10 females and 18 males) among the 77 patients available for follow-up. Standardized mortality ratios (SMR) were calculated with mortality data from the general population and from this group of patients with WG (an SMR of 1 indicates that expected and observed survival are identical). Overall survivorship among patients with WG was substantially reduced in this cohort (SMR = 4.685 +/- 0.65; for females SMR = 6.814 +/- 1.571; for males SMR = 3.998 +/- 0.69). CONCLUSION: The life expectancy of patients with WG is reduced compared with the general population.

Long-term survival of patients with giant cell arteritis in the American College of Rheumatology giant cell arteritis classification criteria cohort.

OBJECTIVE: To characterize survivorship among patients with giant cell arteritis in a well-defined, multicenter cohort. PATIENTS AND METHODS: Follow-up was obtained for 205 (95.8%) of the 214 patients enrolled in the 1990 American College of Rheumatology vasculitis classification study. Standardized mortality ratios (SMR) were calculated comparing mortality data from this group of patients with giant cell arteritis versus the general population. RESULTS: There were 49 deaths (33 women and 16 men among the 205 patients available for follow-up. Survivorship was virtually identical to that of the general population (SMR = 1.034 +/- 0.121), and was similar for women (SMR = 1.022 +/- 0.149) and men (SMR = 1.078 +/- 0.206) (SMR = 1 indicates that expected and observed survival are identical). CONCLUSION: The life expectancy of patients with giant cell arteritis is the same as that of the general population.

Television viewing and pediatric hypercholesterolemia.

Cholesterol screening for children is recommended currently only for those with a family history of premature coronary heart disease or hyperlipidemia. The authors report on a pediatric-office-based cholesterol screening program where the predictive values of family history indicators were evaluated along with reported television viewing, physical activity, and dietary habits in 1081 children (aged 2 to 20 years, mean 7.4 +/- 3.6 [SD] years). Eight percent of these children had a total cholesterol value of 200 mg/dL or higher; 53% of such children reported watching 2 or more hours of television daily compared with 34% of children with lower cholesterol levels. Multivariate analyses revealed that excessive television viewing was the strongest predictor for a child to have a cholesterol value of 200 mg/dL or higher, with relative risks of 2.2 for 2 to 4 hours of television viewing per day (P less than .01) and 4.8 for children watching more than 4 hours/day, when compared to those watching less than 2 hours/day (P less than .01). In contrast, a positive family history of a high cholesterol level was only modestly associated with an increased probability of having a high cholesterol level (relative risk = 1.6, P less than .05), and a history of premature myocardial infarction in a parent or grandparent was not associated with a child's cholesterol level. Excessive television viewing was found to be associated with certain dietary and physical activity habits and may prove to be a useful, global marker for several life-style factors predisposing children to hypercholesterolemia.

Effects of intermittent pneumatic calf compression on postoperative thrombin and plasmin activity.

A previous study of neurosurgical patients demonstrated an imbalance between thrombin and plasmin action following surgery. The present study was designed to determine the effect of intermittent pneumatic calf compression on postoperative enzyme activity. Fibrinopeptide A (FPA) and B beta 1-42 levels, reflecting thrombin and plasmin action respectively, were measured daily in patients undergoing elective craniotomy. Two of 9 patients not receiving calf compression developed positive fibrinogen leg scans, while none of 5 patients receiving prophylaxis had positive scans. Calf compression was associated with a markedly altered pattern of changes in the fibrinopeptide values following surgery. Without compression, there was perturbation of the balance between thrombin and plasmin action on the day after surgery as reflected by an increase in the FPA/B beta 1-42 ratio. In contrast, in those receiving prophylaxis there was no change in this ratio on the first postoperative day. Calf compression both blunted the mean postoperative increase in the FPA level (1.8 nM vs 4.7 nM; p less than .05) and augmented the mean B beta 1-42 value (3.0 nM vs 0.2 nM; p less than .05) so that the mean increase in the FPA/B beta 1-42 ratio was only 0.1 with calf compression as compared to 2.2 without it (p less than .05). Systemic modulation of both the coagulation and fibrinolytic pathways thus occurred in association with calf compression.