Book Reviews

Book Review

The Ursinus Weekly, June 8, 1906

A dream of Heaven • The Baccalaureate sermon • Song recital • Class Day • The junior oratorical contest • Commencement • The Charmidean banquet • Society notes • Baseball • Alumni Day • Commencement game • Literary Supplement: A twentieth century renaissance; The college man in public life; Formation of the Schuylkill Valley; Does prevalence of natural science tend to check poetic spirit?; Janice Meredith and the modern girlhttps://digitalcommons.ursinus.edu/weekly/2983/thumbnail.jp

Roles of key active-site residues in flavocytochrome P450 BM3

Abbreviations used: P450, cytochrome P450 mono-oxygenase; ImC12, 12-(imidazolyl)dodecanoic acid; 1-PIM, 1-phenylimidazole.The effects of mutation of key active-site residues (Arg-47, Tyr-51, Phe-42 and Phe-87) in Bacillus megaterium flavocytochrome P450 BM3 were investigated. Kinetic studies on the oxidation of laurate and arachidonate showed that the side chain of Arg-47 contributes more significantly to stabilization of the fatty acid carboxylate than does that of Tyr-51 (kinetic parameters for oxidation of laurate: R47A mutant, Km 859 µM, kcat 3960 min-1; Y51F mutant, Km 432 µM, kcat 6140 min-1; wild-type, Km 288 µM, kcat 5140 min-1). A slightly increased kcat for the Y51F-catalysed oxidation of laurate is probably due to decreased activation energy (DG‡) resulting from a smaller DG of substrate binding. The side chain of Phe-42 acts as a phenyl 'cap' over the mouth of the substrate-binding channel. With mutant F42A, Km is massively increased and kcat is decreased for oxidation of both laurate (Km 2.08 mM, kcat 2450 min-1) and arachidonate (Km 34.9 µM, kcat 14620 min-1; compared with values of 4.7 µM and 17100 min-1 respectively for wild-type). Amino acid Phe-87 is critical for efficient catalysis. Mutants F87G and F87Y not only exhibit increased Km and decreased kcat values for fatty acid oxidation, but also undergo an irreversible conversion process from a 'fast' to a 'slow' rate of substrate turnover [for F87G (F87Y)-catalysed laurate oxidation: kcat 'fast', 760 (1620) min-1; kcat 'slow', 48.0 (44.6) min-1; kconv (rate of conversion from fast to slow form), 4.9 (23.8) min-1]. All mutants showed less than 10% uncoupling of NADPH oxidation from fatty acid oxidation. The rate of FMN-to-haem electron transfer was shown to become rate-limiting in all mutants analysed. For wild-type P450 BM3, the rate of FMN-to-haem electron transfer (8340 min-1) is twice the steady-state rate of oxidation (4100 min-1), indicating that other steps contribute to rate limitation. Active-site structures of the mutants were probed with the inhibitors 12-(imidazolyl)dodecanoic acid and 1-phenylimidazole. Mutant F87G binds 1-phenylimidazole > 10-fold more tightly than does the wild-type, whereas mutant Y51F binds the haem-co-ordinating fatty acid analogue 12-(imidazolyl)dodecanoic acid > 30-fold more tightly than wild-type

An L Band Spectrum of the Coldest Brown Dwarf

The coldest brown dwarf, WISE 0855, is the closest known planetary-mass, free-floating object and has a temperature nearly as cold as the solar system gas giants. Like Jupiter, it is predicted to have an atmosphere rich in methane, water, and ammonia, with clouds of volatile ices. WISE 0855 is faint at near-infrared wavelengths and emits almost all its energy in the mid-infrared. Skemer et al. (2016) presented a spectrum of WISE 0855 from 4.5–5.1 µm (M band), revealing water vapor features. Here, we present a spectrum of WISE 0855 in L band, from 3.4–4.14 µm. We present a set of atmosphere models that include a range of compositions (metallicities and C/O ratios) and water ice clouds. Methane absorption is clearly present in the spectrum. The mid-infrared color can be better matched with a methane abundance that is depleted relative to solar abundance. We find that there is evidence for water ice clouds in the M band spectrum, and we find a lack of phosphine spectral features in both the L and M band spectra. We suggest that a deep continuum opacity source may be obscuring the near-infrared flux, possibly a deep phosphorous-bearing cloud, ammonium dihyrogen phosphate. Observations of WISE 0855 provide critical constraints for cold planetary atmospheres, bridging the temperature range between the long-studied solar system planets and accessible exoplanets. JWST will soon revolutionize our understanding of cold brown dwarfs with high-precision spectroscopy across the infrared, allowing us to study their compositions and cloud properties, and to infer their atmospheric dynamics and formation processes

An L Band Spectrum of the Coldest Brown Dwarf

The coldest brown dwarf, WISE 0855, is the closest known planetary-mass, free-floating object and has a temperature nearly as cold as the solar system gas giants. Like Jupiter, it is predicted to have an atmosphere rich in methane, water, and ammonia, with clouds of volatile ices. WISE 0855 is faint at near-infrared wavelengths and emits almost all its energy in the mid-infrared. Skemer et al. 2016 presented a spectrum of WISE 0855 from 4.5-5.1 micron (M band), revealing water vapor features. Here, we present a spectrum of WISE 0855 in L band, from 3.4-4.14 micron. We present a set of atmosphere models that include a range of compositions (metallicities and C/O ratios) and water ice clouds. Methane absorption is clearly present in the spectrum. The mid-infrared color can be better matched with a methane abundance that is depleted relative to solar abundance. We find that there is evidence for water ice clouds in the M band spectrum, and we find a lack of phosphine spectral features in both the L and M band spectra. We suggest that a deep continuum opacity source may be obscuring the near-infrared flux, possibly a deep phosphorous-bearing cloud, ammonium dihyrogen phosphate. Observations of WISE 0855 provide critical constraints for cold planetary atmospheres, bridging the temperature range between the long-studied solar system planets and accessible exoplanets. JWST will soon revolutionize our understanding of cold brown dwarfs with high-precision spectroscopy across the infrared, allowing us to study their compositions and cloud properties, and to infer their atmospheric dynamics and formation processes.Comment: 19 pages, 21 figures. Accepted for publication in Ap

Whole-body MRI compared with standard pathways for staging metastatic disease in lung and colorectal cancer: the Streamline diagnostic accuracy studies.

BACKGROUND: Whole-body magnetic resonance imaging is advocated as an alternative to standard pathways for staging cancer. OBJECTIVES: The objectives were to compare diagnostic accuracy, efficiency, patient acceptability, observer variability and cost-effectiveness of whole-body magnetic resonance imaging and standard pathways in staging newly diagnosed non-small-cell lung cancer (Streamline L) and colorectal cancer (Streamline C). DESIGN: The design was a prospective multicentre cohort study. SETTING: The setting was 16 NHS hospitals. PARTICIPANTS: Consecutive patients aged ≥ 18 years with histologically proven or suspected colorectal (Streamline C) or non-small-cell lung cancer (Streamline L). INTERVENTIONS: Whole-body magnetic resonance imaging. Standard staging investigations (e.g. computed tomography and positron emission tomography-computed tomography). REFERENCE STANDARD: Consensus panel decision using 12-month follow-up data. MAIN OUTCOME MEASURES: The primary outcome was per-patient sensitivity difference between whole-body magnetic resonance imaging and standard staging pathways for metastasis. Secondary outcomes included differences in specificity, the nature of the first major treatment decision, time and number of tests to complete staging, patient experience and cost-effectiveness. RESULTS: Streamline C - 299 participants were included. Per-patient sensitivity for metastatic disease was 67% (95% confidence interval 56% to 78%) and 63% (95% confidence interval 51% to 74%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -5% to 13%; p = 0.51). Specificity was 95% (95% confidence interval 92% to 97%) and 93% (95% confidence interval 90% to 96%) respectively, a difference of 2% (95% confidence interval -2% to 6%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 96% and 95% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 8 days (95% confidence interval 6 to 9 days) and 13 days (95% confidence interval 11 to 15 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 5 days (95% confidence interval 3 to 7 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £216 (95% confidence interval £211 to £221) versus £285 (95% confidence interval £260 to £310). Streamline L - 187 participants were included. Per-patient sensitivity for metastatic disease was 50% (95% confidence interval 37% to 63%) and 54% (95% confidence interval 41% to 67%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -7% to 15%; p = 0.73). Specificity was 93% (95% confidence interval 88% to 96%) and 95% (95% confidence interval 91% to 98%), respectively, a difference of 2% (95% confidence interval -2% to 7%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 98% and 99% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 13 days (95% confidence interval 12 to 14 days) and 19 days (95% confidence interval 17 to 21 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 6 days (95% confidence interval 4 to 8 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £317 (95% confidence interval £273 to £361) versus £620 (95% confidence interval £574 to £666). Participants generally found whole-body magnetic resonance imaging more burdensome than standard imaging but most participants preferred the whole-body magnetic resonance imaging staging pathway if it reduced time to staging and/or number of tests. LIMITATIONS: Whole-body magnetic resonance imaging was interpreted by practitioners blinded to other clinical data, which may not fully reflect how it is used in clinical practice. CONCLUSIONS: In colorectal and non-small-cell lung cancer, the whole-body magnetic resonance imaging staging pathway has similar accuracy to standard staging pathways, is generally preferred by patients, improves staging efficiency and has lower staging costs. Future work should address the utility of whole-body magnetic resonance imaging for treatment response assessment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN43958015 and ISRCTN50436483. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 66. See the NIHR Journals Library website for further project information

Quietly sharing the load? The role of school psychologists in enabling teacher resilience

Teacher resilience is associated with positive student outcomes and plays an important role in teacher retention and well-being. School ecologies can enable the resilience of teachers, with prior research illustrating the importance of supportive colleagues, strong leadership, and positive school culture. There is limited research, however, exploring the role of school psychologists in supporting or enabling teacher resilience. Using data from experienced Australian school psychologists and teachers, this exploratory qualitative study examines the role of school psychologists in enabling teacher resilience. Findings show that school psychologists directly and indirectly support teacher resilience, although teachers perceive school psychologists’ main role as work with individual students. Issues pertaining to variations in access and particular roles of school psychologists are discussed. Although further research is needed to clarify and promote the role of school psychologists, this study points to them potentially playing an important role in school ecologies that enable teacher resilience

Suicide prevention in primary care: General practitioners' views on service availability

BackgroundPrimary care may be a key setting for suicide prevention. However, comparatively little is known about the services available in primary care for suicide prevention. The aims of the current study were to describe services available in general practices for the management of suicidal patients and to examine GPs views on these services. We carried out a questionnaire and interview study in the North West of England. We collected data on GPs views of suicide prevention generally as well as local mental health service provision.FindingsDuring the study period (2003-2005) we used the National Confidential Inquiry Suicide database to identify 286 general practitioners (GPs) who had registered patients who had died by suicide. Data were collected from GPs and practice managers in 167 practices. Responses suggested that there was greater availability of services and training for general mental health issues than for suicide prevention specifically. The three key themes which emerged from GP interviews were: barriers accessing primary or secondary mental health services; obstacles faced when referring a patient to mental health services; managing change within mental health care servicesConclusionsHealth professionals have an important role to play in preventing suicide. However, GPs expressed concerns about the quality of primary care mental health service provision and difficulties with access to secondary mental health services. Addressing these issues could facilitate future suicide prevention in primary care