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Buprenorphine formulations (including buprenorphine/naloxone) are effective treatments of pain and opioid use disorder (OUD). Historically, perioperative management of patients prescribed buprenorphine involved abstinence from buprenorphine sufficient to allow for unrestricted mu-opioid receptor availability to full agonist opioid (FAO) treatment. Evidence is mounting that a multimodal analgesic strategy, including simultaneous administration of buprenorphine and FAO, nonopioid adjuncts such as acetaminophen and nonsteroidal anti-inflammatory drugs, and regional anesthesia, is a safe and effective perioperative strategy for the patient prescribed long-term buprenorphine treatment of OUD. This strategy will likely simplify management and more seamlessly provide continuous buprenorphine treatment of OUD after hospital discharge.

ObjectiveThis study aimed to systematically review and meta-analyse the incidence and prevalence of hamstring injuries in field-based team sports. A secondary aim was to determine the impact of other potential effect moderators (match vs training; sport; playing surface; cohort age, mass and stature; and year when data was collected) on the incidence of hamstring injury in field-based team sports.DesignSystematic review and meta-analysis.Data sourcesCINAHL, Cochrane Library, MEDLINE Complete (EBSCO), Embase, Web of Science and SPORTDiscus databases were searched from database inception to 5 August 2020.Eligibility criteriaProspective cohort studies that assessed the incidence of hamstring injuries in field-based team sports.MethodFollowing database search, article retrieval and title and abstract screening, articles were assessed for eligibility against predefined criteria then assessed for methodological quality using the Critical Appraisal Tool for prevalence studies. Meta-analysis was used to pool data across studies, with meta-regression used where possible.ResultsSixty-three articles were included in the meta-analysis, encompassing 5952 injuries and 7 262 168 hours of exposure across six field-based team sports (soccer, rugby union, field hockey, Gaelic football, hurling and Australian football). Hamstring injury incidence was 0.81 per 1000 hours, representing 10% of all injuries. Prevalence for a 9-month period was 13%, increasing 1.13-fold for every additional month of observation (p=0.004). Hamstring injury incidence increased 6.4% for every 1 year of increased average cohort age, was 9.4-fold higher in match compared with training scenarios (p=0.003) and was 1.5-fold higher on grass compared with artificial turf surfaces (pConclusionHamstring injury represents 10% of all injuries in field-based team sports, with 13% of the athletes experiencing a hamstring injury over a 9-month period most commonly during matches. More work is needed to reduce the incidence of hamstring injury in field-based team sports.PROSPERO registration numberCRD42020200022.

Background: Colonoscopy follow-up recommendations depend on the presence or absence of polyps, and if found, their number, size, and histology. Patients may be responsible for conveying results between primary and specialty care or providing medical information to family members; thus, accurate reporting is critical. This analysis assessed the accuracy of self-reported colonoscopy findings. Methods: 3,986 participants from the Study of Colonoscopy Utilization, an ancillary study nested within the Prostate, Lung, Colorectal, and Ovarian Screening Trial, were included. Self-reports of polyp and adenoma were compared to medical records, and measures of sensitivity and specificity were calculated. Correlates of accurate self-report of polyp were assessed using logistic regression and weighted to account for study sampling. Results: The sensitivity and specificity of self-reported polyp findings were 88% and 85%, respectively, and for adenoma 11% and 99%, respectively. Among participants with a polyp, older age was associated with lower likelihood while polyp severity and non-white race were associated with increased likelihood of accurate recall. Among participants without a polyp, having multiple colonoscopies was associated with lower likelihood while family history of colorectal cancer was associated with increased likelihood of accurate recall. Among both groups, longer time since colonoscopy was associated with lower likelihood of accurate recall. Conclusions: Participants recalled with reasonable accuracy whether they had a prior polyp; however, recall of histology, specifically adenoma, was much less accurate. Impact: Identification of strategies to increase accurate self-report of colonic polyps are needed, particularly for patient–provider communications and patient reporting of results to family members.

Buprenorphine formulations (including buprenorphine/naloxone) are effective treatments of pain and opioid use disorder (OUD). Historically, perioperative management of patients prescribed buprenorphine involved abstinence from buprenorphine sufficient to allow for unrestricted mu-opioid receptor availability to full agonist opioid (FAO) treatment. Evidence is mounting that a multimodal analgesic strategy, including simultaneous administration of buprenorphine and FAO, nonopioid adjuncts such as acetaminophen and nonsteroidal anti-inflammatory drugs, and regional anesthesia, is a safe and effective perioperative strategy for the patient prescribed long-term buprenorphine treatment of OUD. This strategy will likely simplify management and more seamlessly provide continuous buprenorphine treatment of OUD after hospital discharge.

Stripe rust caused by Puccnina striiformis (Pst) is an economically important disease attacking wheat all over the world. Identifying and deploying new genes for Pst resistance is an economical and long-term strategy for controlling Pst. A genome-wide association study (GWAS) using single nucleotide polymorphisms (SNPs) and functional haplotypes were used to identify loci associated with stripe rust resistance in synthetic-derived (SYN-DER) wheats in four environments. In total, 92 quantitative trait nucleotides (QTNs) distributed over 65 different loci were associated with resistance to Pst at seedling and adult plant stages. Nine additional loci were discovered by the linkage disequilibrium-based haplotype-GWAS approach. The durable rust-resistant gene Lr34/Yr18 provided resistance in all four environments, and against all the five Pst races used in this study. The analysis identified several SYN-DER accessions that carried major genes: either Yr24/Yr26 or Yr32. New loci were also identified on chr2B, chr5B, and chr7D, and 14 QTNs and three haplotypes identified on the D-genome possibly carry new alleles of the known genes contributed by the Ae. tauschii founders. We also evaluated eleven different models for genomic prediction of Pst resistance, and a prediction accuracy up to 0.85 was achieved for an adult plant resistance, however, genomic prediction for seedling resistance remained very low. A meta-analysis based on a large number of existing GWAS would enhance the identification of new genes and loci for stripe rust resistance in wheat. The genetic framework elucidated here for stripe rust resistance in SYN-DER identified the novel loci for resistance to Pst assembled in adapted genetic backgrounds.

Toll-like receptor (TLR) agonists can act as immune stimulants alone or as part of alum or oil formulations. Humoral and cellular immune responses were utilized to assess quantitative and qualitative immune response enhancement by TLR agonists using recombinant protective antigen (rPA) of B. anthracis as a model antigen. To rPA, combined with aluminum hydroxide (Alhydrogel; Al(OH)3) or squalene (AddaVax™), was added one of 7 TLR agonists: TLR2 agonist Pam3CysSK4 (PamS), TLR3 agonist double stranded polyinosinic:polycytidylic acid (PolyIC), TLR4 agonists Monophosphoryl lipid A (MPLA) or glucopyranosyl lipid A (GLA), TLR7-8 agonists 3M-052 or Resiquimod (Resiq), or TLR9 agonist CPG 7909 (CPG). CD-1 or BALB/c mice received two intraperitoneal or intramuscular immunizations 14 days apart, followed by serum or spleen sampling 14 days later. All TLR agonists except PamS induced high levels of B. anthracis lethal toxin-neutralizing antibodies and immunoglobulin G (IgG) anti-PA. Some responses were 100-fold higher than those without a TLR agonist, and IP delivery (0.5 mL) induced higher TLR-mediated antibody response increases compared to IM delivery (0.05 mL). TLR7-8 and TLR9 agonists induced profound shifts of IgG anti-PA response to IgG2a or IgG2b. Compared to the 14-day immunization schedule, use of a shortened immunization schedule of only 7 days between prime and boost found that TLR9 agonist CPG in a squalene formulation maintained higher interferon-γ-positive cells than TLR4 agonist GLA. Variability in antibody responses was lower in BALB/c mice than CD-1 mice but antibody responses were higher in CD-1 mice. Lower serum 50% effective concentration (EC50) values were found for rPA-agonist formulations and squalene formulations compared to Al(OH)3 formulations. Lower EC50 values also were associated with low frequency detection of linear peptide epitopes. In summary, TLR agonists elicited cellular immune responses and markedly boosted humoral responses.

Background Treating acute pain among persons with opioid use disorder (OUD) on opioid agonist therapy (OAT) is complex, and the therapeutic benefits of opioids remain unclear when weighted against their abuse potential and respiratory depressant effects. Methods We conducted a systematic review of experimental pain studies examining opioid-induced analgesia among persons with OUD on OAT. We searched multiple databases from inception to July 30, 2021. Study quality was assessed by previously established validity measures. Results Nine studies were identified, with a total of 225 participants, of whom 63% were male, and 37% were female. Six studies included methadone-maintained persons with OUD; four studies included buprenorphine-maintained persons with OUD; and three studies included healthy persons as comparison groups. Either additional doses of OAT or other opioids – morphine, oxycodone, hydromorphone, or remifentanil – were administered. In seven studies, persons with OUD on OAT did not experience analgesia, despite receiving opioid doses up to 20 times greater than those clinically used to treat severe pain among the opioid naive. Conversely, in two studies, high-potency opioids did produce analgesia, albeit with greater abuse potential. Notably, persons with OUD on OAT remained vulnerable to respiratory depression. Conclusions Although persons with OUD on OAT can derive analgesic effects from opioids, high-potency compounds may be required to achieve clinically significant pain relief. Further, persons with OUD on OAT may remain vulnerable to opioid-induced abuse potential and respiratory depression. Together, these finding have clinical, methodological, and mechanistic implications for the treatment of acute pain in the context of OAT.

Background With advancing therapeutics, lung cancer (LC) survivors are rapidly increasing in number. Although mounting evidence suggests LC survivors have high risk of second primary lung cancer (SPLC), there is no validated prediction model available for clinical use to identify high-risk LC survivors for SPLC. Methods Using data from 6325 ever-smokers in the Multiethnic Cohort (MEC) study diagnosed with initial primary lung cancer (IPLC) in 1993-2017, we developed a prediction model for 10-year SPLC risk after IPLC diagnosis using cause-specific Cox regression. We evaluated the model’s clinical utility using decision curve analysis and externally validated it using 2 population-based data—Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and National Lung Screening Trial (NLST)—that included 2963 and 2844 IPLC (101 and 93 SPLC cases), respectively. Results Over 14 063 person-years, 145 (2.3%) ever-smoking IPLC patients developed SPLC in MEC. Our prediction model demonstrated a high predictive accuracy (Brier score = 2.9, 95% confidence interval [CI] = 2.4 to 3.3) and discrimination (area under the receiver operating characteristics [AUC] = 81.9%, 95% CI = 78.2% to 85.5%) based on bootstrap validation in MEC. Stratification by the estimated risk quartiles showed that the observed SPLC incidence was statistically significantly higher in the 4th vs 1st quartile (9.5% vs 0.2%; P Conclusions We developed and validated a SPLC prediction model based on large population-based cohorts. The proposed prediction model can help identify high-risk LC patients for SPLC and can be incorporated into clinical decision making for SPLC surveillance and screening.

The patient population seen in our nation's Veterans Affairs Healthcare system is increasingly female and an alarming percentage of our veterans, male and female alike, report a history of military sexual trauma (MST), which is associated with an increased burden of morbidities including post-traumatic stress disorder (PTSD) and substance abuse. The experience of surgery can produce symptoms of PTSD in a clinically significant percentage of patients. This article describes the challenges of achieving a patient-centered perioperative care plan in the case of a female veteran who suffers from PTSD as a result of MST.We provide a brief background on the changing demographics of our nation's veterans, a review of MST and patient-centered care, and a description of the interdisciplinary care plan created and implemented for our patient. We note how this care model employs key elements of the Perioperative Surgical Home Model as developed by the American Society of Anesthesiologists. Finally, we propose an agenda for improving perioperative care for this group of veterans. No institutional review board was required for this case report-based discussion.The patient-centered care plan developed and implemented by an interdisciplinary team was well received by the patient and enabled her to comply with her postsurgical physical therapy. This recent interdisciplinary experience was in stark contrast to her experience of former surgical procedures, and produced much higher patient satisfaction.Improvements are needed in patient-centered perioperative care for victims of MST, both within the Veterans Affairs system and in the larger health care system. We suggest an agenda to improve care for these patients including: (1) increasing provider awareness and education about MST and about the potential psychological trauma of surgery per se, (2) employing elements of the Perioperative Surgical Home to encourage patient-centered care involving collaboration within an interdisciplinary team, (3) and measurement of patient centered outcomes. Perioperative care for the victim of MST is heretofore not addressed in the literature. We hope this case report and review will stimulate further research into optimizing care for these vulnerable patients.

A 99-year-old veteran, his family, and an anesthesiologist practice shared decision making to ensure patient-centered care before a procedure.

Code status discussions (CSDs) clarify patient preferences for cardiopulmonary resuscitation in the event of cardiac or respiratory arrest. CSDs are a key component of perioperative care, particularly at the end of life, and must be both patient-centered and shared. Physicians at all levels of training are insufficiently trained in and inappropriately perform CSD; this may be particularly true of perioperative physicians. In this article, we describe the difficulty of achieving a patient-centered, shared perioperative CSD in the case of a medical professional with a do-not-resuscitate order. We provide a brief background in cardiopulmonary resuscitation, do-not-resuscitate, and CSD before proposing an agenda for improving perioperative CSD.

Background: Lung cancer (LC) survivors in the U.S. are increasing in number, with 5-year survival rates improving by 26% over the past decade. Although LC survivors are at high risk of developing a second primary lung cancer (SPLC), risk factors for SPLC have not been established and the impact of tobacco smoking remains controversial. In this study, we examined risk factors for SPLC among participants in the Multiethnic Cohort (MEC) study, validated our findings with two epidemiologic cohorts–the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and the European Prospective Investigation into Cancer and Nutrition (EPIC)–and evaluated the impact of smoking cessation on SPLC risk. Methods: We analyzed data from 7,299 initial primary lung cancer (IPLC) cases in MEC who were diagnosed from 1993-2017. Incident IPLC and SPLC were identified via linkage to SEER registries, with SPLC defined by Martini and Melamed criteria. Baseline smoking data were obtained at the time of enrollment (1993-1996) and updated with 10-year follow-up data close to IPLC diagnosis, if available. Fine-Gray regression was used to take into account competing risks and to evaluate the associations between risk factors and SPLC, adjusting for age at IPLC diagnosis and IPLC histology and stage. We conducted validation studies with PLCO (N=3,423 LC patients) and EPIC (N=4,605 LC patients) and evaluated the combined effects of risk factors from all three cohorts using meta-analysis. Results: Among 7,299 MEC participants with IPLC, 167 (2.3%) developed a SPLC. Fine-Gray regression analyses identified several factors that were significantly associated with SPLC risk (P Conclusions: Smoking is a risk factor for SPLC among LC patients and the USPSTF criteria can potentially aid in identifying those at high risk of SPLC. Smoking cessation may reduce SPLC risk after IPLC diagnosis. Further analysis is required to stratify SPLC risk based on comprehensive risk factors and identify LC survivors at high risk of SPLC for CT screening. Citation Format: Jacqueline V. Aredo, Sophia J. Luo, Rebecca Gardner, Thomas P. Hickey, Thomas L. Riley, Lynne R. Wilkens, Loic Le Marchand, Christopher I. Amos, Rayjean J. Hung, Mattias Johansson, Iona Cheng, Heather A. Wakelee, Summer S. Han. Is smoking a risk factor for second primary lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2298.

Managing pain in the patient with substance use disorder can be challenging. This chapter describes those challenges and provides strategies to address them. Specifically it discusses the prevalence and specific considerations for commonly abused substances, the need for aggressive communication among perioperative clinicians, and a strategy to decrease acute postoperative pain and associated complications using opioid-sparing, multimodal analgesia. It includes a discussion of the concept of equianalgesic opioid doses and management of opioid-related side effects including respiratory depression, with regard to buprenorphine, naltrexone, and methadone. Specific consideration is given to the surgical patient treated with buprenorphine, and a defined clinical plan is outlined.

Acute and chronic substance abuse can adversely affect the perioperative course of maxillofacial surgery. Addictive substances modulate the brains reward pathways and manifest with altered behaviors. Substance use can affect all major organ systems, and identification of patients who are at risk will help minimize perioperative complications. Challenges include preoperative optimization, intraoperative management, and postoperative withdrawal treatment. Multimodal analgesia, with emphasis on regional and non-opioid medications, is recommended. Should postoperative withdrawal develop, prompt and effective treatment is warranted.

In this brief review of one-lung ventilation (OLV), we present the case of a patient with lung cancer scheduled to undergo thoracoscopic lobectomy. We review the functional anatomy of the lung, essential components of the preoperative evaluation, concerns specific to patients with lung cancer, smoking cessation, lung isolation techniques with attendant advantages and disadvantages, ventilation/perfusion matching, approaches to hypoxemia and high peak airway pressures during OLV, hypoxemic pulmonary vasoconstriction, perioperative concerns in patients with chronic obstructive pulmonary disease, appropriate intraoperative monitoring in lobectomy, thoracic epidural analgesia, fluid management in thoracic surgery, extubation criteria, and postoperative management.

We determined the modified Gleason grade of prostatic adenocarcinomas detected in PLCO to assess grade distribution and compare modified Gleason grades of cancer detected in the intervention arm (organized annual screening) vs the control arm (opportunistic screening).Modified Gleason grading was performed in 859 radical prostatectomy cases by a single urological pathologist. We compared the proportion of cases with high grade disease in the screened arm vs the control arm by logistic regression analysis.In the intervention arm a modified Gleason score of 5, 6, 7 (3+4), 7 (4+3), 8, 9 and 10 was assigned in 3.6%, 43.3%, 39%, 7.4%, 3.5%, 3.2% and 0.1% of cases, respectively. In the control arm a modified Gleason score of 5, 6, 7 (3+4), 7 (4+3), 8, 9 and 10 was assigned in 3.0%, 35.7%, 46.4%, 7.1%, 5.4%, 1.9% and 0.5% of cases, respectively, after correcting for high grade disease over sampling. A high grade modified Gleason score of 7 or greater was detected in 53% of cases in the intervention arm vs 61.3% in the control arm after correction (p=0.019). The median modified Gleason score was 7 (3+4) in each arm.A significant percent of cancers in each arm had a component of high grade disease. The modified Gleason grade of prostate cancers detected by organized annual screening was slightly lower than the modified grade of those detected by opportunistic screening. This is an expected consequence of more intensive screening.

Background: Previous studies have shown an inverse relationship between prostate-specific antigen (PSA) concentration and body mass index (BMI). It has been recently proposed that this relationship may be explained by the larger plasma volume of obese men diluting a fixed amount of PSA (hemodilution effect). We examined this hypothesis in a cohort of men enrolled in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: Of 38,349 men ages 55 to 74 years randomized in PLCO to receive annual PSA and digital rectal examination screening, 28,380 had a baseline PSA, complete demographic information, and no prostate cancer diagnosis within 6 years from baseline. Self-reported height and weight were used to calculate BMI and to estimate plasma volume. PSA mass was estimated as PSA concentration times plasma volume. Multivariable linear regression models were used to investigate the relationship between PSA concentration, plasma volume, PSA mass, and BMI. Results: PSA concentration significantly decreased with increasing BMI (P < 0.001); mean PSA values were 1.27, 1.25, 1.18, and 1.07 ng/mL among normal (BMI, 18.5-25), overweight (BMI, 25-30), obese (BMI, 30-35), and morbidly obese (BMI, >35) men, respectively. However, plasma volume also increased with increasing BMI and PSA mass showed no association with BMI, with mean values of 3.78, 3.95, 3.97, and 3.82 μg across the four BMI categories (P = 0.10). Conclusions: This study confirms earlier findings that the inverse relationship between PSA concentration and BMI may be explained by a hemodilution effect. These findings could have implications for prostate cancer screening in large men. (Cancer Epidemiol Biomarkers Prev 2009;18(3):748–51)

From the carbolithiation of 6-N,N-dimethylamino fulvene (3a) and different lithiated N-heterocyclic compounds (N,N-dimethylaminomethylpyrrole, 1-methylimidazole and 2,4-[bis(N',N'-dimethylaminomethyl)]-N-methyl pyrrole), the corresponding lithium cyclopentadienide intermediate (4a-c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4 resulting in dimethylamino-functionalised titanocenes 5a-c. When these titanocenes were tested against LLC-PK cells, the IC50 values obtained were of 13, and 63 microM for titanocenes 5b and 5c, respectively. The most cytotoxic titanocene in this paper (5a) with an IC50 value of 6.8 microM is found to be almost as cytotoxic as cis-platin, which showed an IC50 value of 3.3 microM, when tested on the epithelial pig kidney LLC-PK cell line, and titanocene 5c is approximately 400 times better than titanocene dichloride itself.

We selected 40 candidate Lyα-emitting galaxies (LAEs) at z 3.1 with observed-frame equivalent widths greater than 150 A and inferred emission-line fluxes above 2.5 × 10-17 ergs cm-2 s-1 from deep narrowband and broadband MUSYC images of the Extended Chandra Deep Field South. Covering 992 arcmin2, this is the largest blank field surveyed for LAEs at z ~ 3, allowing an improved estimate of the space density of this population of (3 ± 1) × 10-4 h Mpc-3. Spectroscopic follow-up of 23 candidates yielded 18 redshifts, all at z 3.1. Over 80% of the LAEs are dimmer in continuum magnitude than the typical Lyman break galaxy (LBG) spectroscopic limit of R = 25.5 (AB), with a median continuum magnitude R 27 and very blue continuum colors, V-z 0. Over 80% of the LAEs have the right UVR colors to be selected as LBGs, but only 10% also have R ≤ 25.5. Stacking the UBVRIzJK fluxes reveals that LAEs have stellar masses 5 × 108 h M☉ and minimal dust extinction, AV 0.1. Inferred star formation rates are 6 h M☉ yr-1, yielding a cosmic star formation rate density of 2 × 10-3 h70 M☉ yr-1 Mpc-3. None of our LAE candidates show evidence for rest-frame emission-line equivalent widths EWrest > 240 A that might imply a nonstandard initial mass function. One candidate is detected by Chandra, implying an AGN fraction of 2% ± 2% for LAE candidate samples. In summary, LAEs at z ~ 3 have rapid star formation, low stellar mass, little dust obscuration, and no evidence for a substantial AGN component.

THERE HAS BEEN A DRAMATIC INCREASE in detection of Takotsubo cardiomyopathy (also known as stress-induced cardiomyopathy or broken heart syndrome) since its initial description. Takotsubo cardiomyopathy has been reported in the presence of various physiologic stressors such as noncardiac surgery, pneumothorax, alcohol withdrawal, hypoglycemia, and myasthenic crisis. Emotional and/or physiologic stress, chest pain, ST elevation on electrocardiogram (ECG), elevated troponins, left ventricular (LV) apical hypokinesis/ ballooning, and absence of any coronary arterial lesion have been used as clinical criteria for diagnosis. Female predominance (85%) has been noted along with increasing risk with age. Differentiation of Takotsubo from acute coronary syndromes has proven problematic without cardiac catheterization. ECG findings have been studied, and while reciprocal T wave changes in Takotsubo are less common than in acute coronary syndrome, they still occur in a significant portion of cases. The authors present case details and review literature on intraoperative Takotsubo, especially as it pertains to patients with a history of pheochromocytoma/paraganglioma.

Since 1964, public administrators in the United States have been faced with the challenge of providing discrimination-free employment opportunities. To attain this goal, many employers have instituted affirmative action programs but the legal status of these highly controversial programs is unclear. This article provides a concise overview of the legal issues in affirmative action programs. It analyzes recent statutory and case law developments in an effort to gain insight into the future of affirmative action programs.

The Fifth Amendment Double Jeopardy Clause safeguards vital interests of the accused in criminal proceedings. That clause does not, however, prevent the government from retrying a criminal defendant after a hung jury mistrial. This is because a “manifest necessity” justifies declaring a mistrial in these circumstances. Also, if a defendant's trial ends in a hung jury, his original jeopardy is not terminated. Retrial in these cases also is permitted because of an important governmental interest in a full opportunity to prosecute its criminal cases. Byron De La Beckwith was recently convicted of the 1963 murder of Medgar Evers, an early civil rights leader. This was the third time in approximately thirty years that the state of Mississippi had charged Beckwith with this crime. The first two trials, which took place in 1964, ended in hung jury mistrials. This article examines the double jeopardy implications of Beckwith's latest conviction and recommends that the courts adopt a more flexible standard for determining if a defendant should be retried after a hung jury mistrial. The proposed rule would place greater emphasis on an accused's important double jeopardy interests including finality and action limitation, in not allowing the government to gain a tactical advantage by manipulating criminal proceedings, and in preventing the prosecution from fine-tuning its trial strategy.

Although colorectal cancer (CRC) prognosis is improved by early diagnosis, screening rates remain low.To determine the effect of an automated telephone intervention on completion of fecal occult blood testing (FOBT).In this randomized controlled trial conducted at Kaiser Permanente Northwest, a not-for-profit health maintenance organization, 5905 eligible patients aged 51 to 80, at average risk for CRC and due for CRC screening, were randomly assigned to an automated telephone intervention (n = 2943) or usual care (UC; n = 2962). The intervention group received up to three 1-minute automated telephone calls that provided a description and health benefits of FOBT. During the call, patients could request that an FOBT kit be mailed to their home. Those who requested but did not return the cards received an automated reminder call. Cox proportional hazard method was used to determine the independent effect of automated telephone calls on completion of an FOBT, after adjusting for age, sex, and prior CRC screening.By 6 months after call initiation, 22.5% in the intervention and 16.0% in UC had completed an FOBT. Those in the intervention group were significantly more likely to complete an FOBT (hazard ratio, 1.31; 95% confidence interval, 1.10-1.56) compared with UC. Older patients (aged 71-80 vs. aged 51-60) were also more likely to complete FOBT (hazard ratio, 1.48; 95% confidence interval, 1.07-2.04).Automated telephone calls increased completion of FOBT. Further research is needed to evaluate automated telephone interventions among diverse populations and in other clinical settings.

It is unclear whether the disproportionately higher incidence and mortality from colorectal cancer among blacks compared with whites reflect differences in health-care utilization or colorectal cancer susceptibility.A total of 60, 572 non-Hispanic white and black participants in the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial underwent trial-sponsored screening flexible sigmoidoscopy (FSG) without biopsy at baseline in 10 geographically dispersed centers from November 1993 to July 2001. Subjects with polyps or mass lesions detected by FSG were referred to their physicians for diagnostic workup, the cost of which was not covered by PLCO. The records of follow-up evaluations were collected and reviewed. We used log binomial modeling with adjustment for age, education, sex, body mass index, smoking, family history of colorectal cancer, colon examination within previous 3 years, personal history of polyps, and screening center to examine whether utilization of diagnostic colonoscopy and yield of neoplasia differed by race.Among 57 561 whites and 3011 blacks who underwent FSG, 13,743 (23.9%) and 767 (25.5%) had abnormal examinations, respectively. A total of 9944 (72.4%) whites and 480 (62.6%) blacks had diagnostic colonoscopy within 1 year following the abnormal FSG screening. When compared with whites, blacks were less likely to undergo diagnostic evaluation (adjusted risk ratio = 0.88, 95% confidence interval = 0.83 to 0.93). Overall, among subjects with diagnostic colonoscopy (n = 10 424), there was no statistically significant difference by race in the prevalence of adenoma, advanced adenoma, advanced pathology in small adenomas (high-grade dysplasia or villous histology in adenomas10 mm), or colorectal cancer.We observed a lower follow-up for screen-detected abnormalities among blacks when compared with whites but little difference in the yield of colorectal neoplasia. Health-care utilization may be playing more of a role in colorectal cancer racial disparity than biology.

OBJECTIVE To describe the results of the first four rounds (T0-T3) of prostate cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial (designed to determine the value of screening in the four cancers), that for prostate cancer is evaluating whether annual screening with prostate-specific antigen (PSA) and a digital rectal examination (DRE) reduces prostate cancer-specific mortality. SUBJECTS AND METHODS In all, 38 349 men aged 55–74 years were randomized to undergo annual screening with PSA (abnormal >4.0 ng/mL) and a DRE. The follow-up of abnormal screening results was at the discretion of subjects’ physicians. PLCO staff obtained records related to diagnostic follow-up of positive screen results. RESULTS Compliance with screening decreased slightly from 89% at baseline to 85% at T3. Both PSA positivity rates (range 7.7–8.8% at T0-T3) and DRE positivity rates (range 6.8–7.6% at T0-T3) were relatively constant over time. The positive predictive value (PPV) of a PSA level of >4.0 ng/mL decreased from 17.9% at T0 to 10.4–12.3% at T1-T3; the PPV for DRE (in the absence of a positive PSA test) was constant over time (2.9–3.6%). Cancer was diagnosed in 1902 men (4.9%). Screen-detected cancers at T0 (549) were more likely to be clinical stage III/IV (5.8%) and to have a Gleason score of 7–10 (34%) than screen-detected cancers at T1-T3 (1.5–4.2% stage III/IV and 24–27% Gleason score 7–10 among 1054 cases). CONCLUSION The present findings on serial prostate screening are similar to those reported from other multi-round screening studies. Determining the effect of PSA screening on prostate cancer mortality awaits further follow-up.

From the carbolithiation of 6-N,N-dimethylamino fulvene (3) and 2,4[bis(N,N-dimethylamino)methyl]-N-methylpyrrolyl lithium (2a), N-(N′,N′-dimethylaminomethyl)benzimidazolyl lithium (2b)' or p-(N,N-dimethylamino)methylphenyl lithium (2c), the corresponding lithium cyclopentadienide intermediate (4a–c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4' resulting in N,N-dimethylamino-functionalised titanocenes 5a–c. When these titanocenes were tested against a pig kidney epithelial cell line (LLC-PK), the IC50 values obtained were of 23, and 52 μM for titanocenes 5a and 5b, respectively. The most cytotoxic titanocene in this paper, 5c with an IC50 value of 13 μM, was found to be approximately two times less cytotoxic than its analogue Titanocene C (IC50=5.5 μM) and almost four times less cytotoxic than cisplatin, which showed an IC50 value of 3.3 μM when tested on the LLC-PK cell line.

We describe the results of an extremely deep, 0.28 deg^2 survey for z = 3.1 Ly-alpha emission-line galaxies in the Extended Chandra Deep Field South. By using a narrow-band 5000 Anstrom filter and complementary broadband photometry from the MUSYC survey, we identify a statistically complete sample of 162 galaxies with monochromatic fluxes brighter than 1.5 x 10^-17 ergs cm^-2 s^-1 and observers frame equivalent widths greater than 80 Angstroms. We show that the equivalent width distribution of these objects follows an exponential with a rest-frame scale length of w_0 = 76 +/- 10 Angstroms. In addition, we show that in the emission line, the luminosity function of Ly-alpha galaxies has a faint-end power-law slope of alpha = -1.49 +/- 0.4, a bright-end cutoff of log L^* = 42.64 +/- 0.2, and a space density above our detection thresholds of 1.46 +/- 0.12 x 10^-3 h70^3 galaxies Mpc^-3. Finally, by comparing the emission-line and continuum properties of the LAEs, we show that the star-formation rates derived from Ly-alpha are ~3 times lower than those inferred from the rest-frame UV continuum. We use this offset to deduce the existence of a small amount of internal extinction within the host galaxies. This extinction, coupled with the lack of extremely-high equivalent width emitters, argues that these galaxies are not primordial Pop III objects, though they are young and relatively chemically unevolved., 45 pages, 15 figures, accepted for publication in the Astrophysical Journal

To test the ability of an automated telephone outreach intervention to reduce acute healthcare utilization and improve quality of life among adult asthma patients in a large managed care organization.Randomized clinical trial.Patients with persistent asthma were randomly assigned to telephone outreach (automated = 3389, live caller = 192) or usual care (n = 3367). Intervention participants received 3 outreach calls over a 10-month period. The intervention provided brief, supportive information and flagged individuals with poor asthma control for follow-up by a provider. A survey was mailed to 792 intervention participants and 236 providers after the intervention. Additional feedback was obtained as part of the final intervention contact.The intent-to-treat analysis found no significant differences between the intervention and usual-care groups for medication use, healthcare utilization, asthma control, or quality of life. Post hoc analyses found that, compared with the control group, individuals who actually participated in the intervention were significantly more likely to use inhaled steroids and to have had a routine medical visit for asthma during the follow-up period and less likely to use short-acting beta-agonists. They also reported higher satisfaction with their asthma care and better asthma-specific quality of life. Of surveyed providers, 59% stated the program helped them to clinically manage their asthma patients and 70% thought the program should be continued.This study did not find improved health outcomes in the primary analyses. The intervention was well accepted by providers, however, and the individuals who participated in the calls appeared to have benefited from them. These findings suggest that further studies of automated telephone outreach interventions seem warranted.

Objective The relationship of cognitive impairment to functional status in older adults with schizophrenia was investigated. Patients Ninety-three psychiatric inpatients with schizophrenia between the ages of 65 and 88 years. Two subsets of this sample, consisting of 48 and 24 patients, were studied with a greater number of assessment instruments. Measures The Mini-Mental State Examination (MMSE) was used for brief assessment of overall cognitive functioning, and the Psychogeriatric Dependency Rating Scale (PGDRS) was administered to assess functional status. The cognitive test battery from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and/or an expanded neuropsychological battery, was given to a subset of the patients. Results In the overall sample, patients with greater global cognitive impairment had higher levels of rated impairment on the individual items that comprised the Orientation and Physical, but not Behavior, subscales of the PGDRS. Furthermore, in the two subsamples, specific neuropsychological measures of problem-solving, word list learning, naming and constructional praxis were related to overall measures of outcome. Conclusions Neuropsychological deficit and psychosocial outcome are multi-dimensional entities that relate to one another in complex ways. Copyright © 2001 John Wiley & Sons, Ltd.