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A new, bifunctional glycosylphosphatidylinositol (GPI) derivative containing the highly conserved core structure of all natural GPI anchors with a photoactivable diazirine in the lipid chain and clickable alkynes in the glycan was synthesized by a convergent [3+2] glycosylation strategy with late stage protecting group manipulation and regioselective phosphorylation. The challenges of this synthesis were due to the presence of several distinctive functional groups in the synthetic target, which complicated the protection tactics, in addition to the inherent difficulties associated with GPI synthesis. This bifunctional GPI derivative can cross‐react with molecules in proximity upon photoactivation and be subsequently labeled with other molecular tags via click reaction. Therefore, it should be a valuable probe for biological studies of GPIs, such as analysis of GPI‐interacting membrane proteins, and gaining insights into their functional mechanisms. [ABSTRACT FROM AUTHOR]

Plant function arises from a complex network of structural and physiological traits. Explicit representation of these traits, as well as their connections with other biophysical processes, is required to advance our understanding of plant‐soil‐climate interactions. We used the Terrestrial Regional Ecosystem Exchange Simulator (TREES) to evaluate physiological trait networks in maize. Net primary productivity (NPP) and grain yield were simulated across five contrasting climate scenarios. Simulations achieving high NPP and grain yield in high precipitation environments featured trait networks conferring high water use strategies: deep roots, high stomatal conductance at low water potential ("risky" stomatal regulation), high xylem hydraulic conductivity and high maximal leaf area index. In contrast, high NPP and grain yield was achieved in dry environments with low late‐season precipitation via water conserving trait networks: deep roots, high embolism resistance and low stomatal conductance at low leaf water potential ("conservative" stomatal regulation). We suggest that our approach, which allows for the simultaneous evaluation of physiological traits, soil characteristics and their interactions (i.e., networks), has potential to improve our understanding of crop performance in different environments. In contrast, evaluating single traits in isolation of other coordinated traits does not appear to be an effective strategy for predicting plant performance. Our process‐based model uncovered two beneficial but contrasting trait networks for maize which can be understood by their integrated effect on water use/conservation. Modification of multiple, physiologically aligned, traits were required to bring about meaningful improvements in NPP and yield. [ABSTRACT FROM AUTHOR]

Objective: This study delineates the clinical and molecular spectrum of ANKLE2‐related microcephaly (MIC), as well as highlights shared pathological mechanisms between ANKLE2 and the Zika virus. Methods: We identified 12 individuals with MIC and variants in ANKLE2 with a broad range of features. Probands underwent thorough phenotypic evaluations, developmental assessments, and anthropometric measurements. Brain imaging studies were systematically reviewed for developmental abnormalities. We functionally interrogated a subset of identified ANKLE2 variants in Drosophila melanogaster. Results: All individuals had MIC (z‐score ≤ −3), including nine with congenital MIC. We identified a broad range of brain abnormalities including simplified cortical gyral pattern, full or partial callosal agenesis, increased extra‐axial spaces, hypomyelination, cerebellar vermis hypoplasia, and enlarged cisterna magna. All probands had developmental delays in at least one domain, with speech and language delays being the most common. Six probands had skin findings characteristic of ANKLE2 including hyper‐ and hypopigmented macules. Only one individual had scalp rugae. Functional characterization in Drosophila recapitulated the human MIC phenotype. Of the four variants tested, p.Val229Gly, p.Arg236*, and p.Arg536Cys acted as partial‐loss‐of‐function variants, whereas the c.1421‐1G>C splicing variant demonstrated a strong loss‐of‐function effect. Interpretation: Deleterious variants in the ANKLE2 gene cause a unique MIC syndrome characterized by congenital or postnatal MIC, a broad range of structural brain abnormalities, and skin pigmentary changes. Thorough functional characterization has identified shared pathogenic mechanisms between ANKLE2‐related MIC and congenital Zika virus infection. This study further highlights the importance of a thorough diagnostic evaluation including molecular diagnostic testing in individuals with MIC. [ABSTRACT FROM AUTHOR]

Background: In 2016, the Comprehensive Addiction Recovery Act permitted nurse practitioners (NPs) and physician assistants (PAs) to obtain a waiver to prescribe buprenorphine to treat opioid use disorder (OUD), with the goal of increasing access to this treatment. This study's purpose was to describe the buprenorphine prescribing practices of NPs and PAs and compare the barriers rural and urban providers face delivering treatment. Methods: From the October 2018 Drug Enforcement Administration list of providers with the waiver to prescribe buprenorphine, all rural NPs and PAs (1,057) and a random sample of 500 urban NPs and PAs were surveyed. The questionnaire queried respondents about demographics, prescribing practices, practice characteristics, reimbursement policies, and barriers to prescribing buprenorphine to treat OUD. Results: Of the waivered NPs and PAs, 80.3% reported having prescribed buprenorphine and 71.1% said they were currently accepting new patients with OUD. Providers with the 30‐patient waiver were treating, on average, 13.2 patients; 37.0% were not treating any patients. The most common barrier, cited by half of providers, was concerns about diversion/medication misuse. More rural providers indicated lack of specialty backup and mental health providers as a barrier than urban providers. Never‐prescribers and former‐prescribers reported 6 barriers at significantly higher rates than did current prescribers. More rural providers accepted Medicaid and cash reimbursement than urban providers. Conclusions: NPs and PAs face many of the same barriers to providing buprenorphine as physicians have reported. Interventions to address these barriers have the potential to benefit all providers with the waiver to prescribe buprenorphine. [ABSTRACT FROM AUTHOR]

Introduction: Patients with advanced endometriosis may be at an increased risk of surgical complications following laparoscopic treatment of endometriosis; however, this relationship has not been examined. We sought to identify predictors of major complications following laparoscopic treatment of endometriosis.Material and Methods: A retrospective cohort study of women who underwent laparoscopic treatment of suspected endometriosis between 2009 and 2016 within the Division of Minimally Invasive Gynecologic Surgery at Brigham and Women's Hospital, Boston, MA, USA. Predictors of major perioperative complications were assessed by comparing the characteristics of women who had any major intraoperative or postoperative complication with those of women who had no complication.Results: A total of 397 women underwent laparoscopic treatment of suspected endometriosis including excision of superficial endometriosis (55.4%), excision of deep-infiltrating endometriosis (24.9%), fulguration of endometriosis (38.3%), hysterectomy (23.2%), ovarian cystectomy (35.5%), salpingectomy (18.6%), oophorectomy (15.1%), and bowel resection (1.0%). Women were followed for 60 days following surgery, over which time 18 women (4.5%) had a major perioperative complication. Patient characteristics and preoperative imaging were similar between women with and without complications. Women with advanced endometriosis, including stage III or IV endometriosis, deep-infiltrating endometriosis, or rectovaginal disease, were more likely to have a complication, though this did not reach statistical significance (77.8% of women with a complication versus 56.7% of women without a complication had advanced endometriosis, P = 0.077). Women who had a complication were more likely to have undergone adhesiolysis or ureterolysis (88.9% of women with a complication versus 52.5% without a complication underwent adhesiolysis, P = 0.002; and 61.1% of women with a complication versus 28.8% without a complication underwent ureterolysis, P = 0.003). The total number of procedures was greater for women who had a complication (4.3 ± 1.2 vs 3.2 ± 1.5, P = 0.003). All other procedure characteristics were similar between women with and without complications.Conclusions: Complications following laparoscopic treatment of suspected endometriosis could not be predicted by preoperative patient characteristics or surgical findings of advanced endometriosis. Adhesiolysis, ureterolysis, and an increased number of total procedures may be predictive of perioperative complications, suggesting that surgical complexity as measured by the procedures performed, rather than the disease severity, may increase the risk of a complication compared with women who do not undergo these procedures. [ABSTRACT FROM AUTHOR]

In the face of declining water resources and climatic variability, growth stage-based deficit irrigation may be a feasible approach to enhance agricultural system resilience. A 3-yr experiment was conducted to evaluate the impact of deficit irrigation on maize (Zea mays L.) in the late vegetative (Lveg) and maturation (Mat) growth stages, where phenology, dry leaf weight, aboveground biomass, yield, kernel number, 1000 kernel weight, and grain- filling rate were evaluated. Water deficit during the Lveg stage decreased the kernel number and dry leaf weight, thus decreasing the potential grain-filling rate (less photosynthetic tissue). In contrast with deficit during the Lveg stage, deficit during the Mat stage directly reduced the grain-filling rate and duration and thus had the strongest effect on grain yield. A growth stage interaction was evident, such that the reduction in yield associated with water deficit applied during the Lveg stage was exacerbated by water deficit applied during the Mat stage. Yield reduction was proportional with the severity of the water deficit, in all cases. Nevertheless, water deficit applied during the Mat stage had a larger impact on maize yield compared with water deficit applied during the Lveg stage. If farmers have reduced water allocations but seasonal flexibility in the timing of irrigation water application, they will maximize yield by saving water for reproductive and maturation growth stages. [ABSTRACT FROM AUTHOR]

Aims: To compare individuals with comorbid life‐time post‐traumatic stress disorder (PTSD) and alcohol use disorders [AUD; i.e. no drug use disorders (DUD)] with those with comorbid PTSD and DUD on past‐year prevalence of these disorders, social functioning, life‐time psychiatric comorbidities, and treatment receipt. The comorbid groups were also compared with their single diagnosis counterparts. Design and Setting: Cross‐sectional cohort study using data from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC‐III). Participants: The total sample size was 36 309. Six groups were established: PTSD/AUD, PTSD/DUD, AUD, DUD, PTSD, and neither PTSD nor AUD/DUD. Life‐time prevalence of AUD among those with PTSD/DUD was 80.2% and among those with DUD was 73.8%. Measurements The Alcohol Use Disorder and Associated Disabilities Interview Schedule‐DSM‐5 version assessed life‐time and past‐year psychiatric disorders and treatment receipt. Demographics and social stability indicators were queried. Group characteristics were summarized using weighted means. Prevalences and estimates for adjusted differences in means and adjusted odds ratios (aORs) were derived from multiple linear regression and logistic regression models, respectively. Analyses were conducted in R and accounted for the NESARC‐III's complex survey design, clustering, and non‐response. Findings Compared with those with life‐time PTSD/AUD, those with life‐time PTSD/DUD were significantly less likely to have neither disorder in the past year (PTSD/AUD = 16.1%; PTSD/DUD = 8.5%; aOR = 0.54), and were more likely to report worse social and psychiatric functioning, and to have received both addiction and mental health treatment (PTSD/AUD = 18.4%; PTSD/DUD = 43.2%; aOR = 3.88). Compared with their single disorder counterparts, those with PTSD/DUD reported greater impairment than both groups, whereas the comorbid PTSD/AUD group differed more from the AUD than the PTSD group. Conclusions: People with comorbid PTSD and drug use disorder have greater social and psychiatric impairment and may require different types and intensity of intervention than people with comorbid post‐traumatic stress disorder and alcohol use disorder. [ABSTRACT FROM AUTHOR]

Despite high prevalence and concerning associated problems, little effort has been made to conceptualize the construct of posttraumatic guilt. This investigation examined the theoretical model of trauma-related guilt proposed by Kubany and Watson (2003). This model hypothesizes that emotional and physical distress related to trauma memories partially mediates the relationship between guilt cognitions and posttraumatic guilt. Using path analysis, this investigation (a) empirically evaluated relationships hypothesized in Kubany and Watson's model, and (b) extended this conceptualization by evaluating models whereby guilt cognitions, distress, and posttraumatic guilt were related to posttraumatic stress disorder (PTSD) symptoms depression symptom severity. Participants were male U.S. Iraq and Afghanistan veterans ( N = 149). Results yielded a significant indirect effect from guilt cognitions to posttraumatic guilt via distress, providing support for Kubany and Watson's model (β = .14). Findings suggested distress may be the strongest correlate of PTSD symptoms (β = .47) and depression symptoms (β = .40), and that guilt cognitions may serve to intensify the relationship between distress and posttraumatic psychopathology. Research is needed to evaluate whether distress specific to guilt cognitions operates differentially on posttraumatic guilt when compared to distress more broadly related to trauma memories. [ABSTRACT FROM AUTHOR]

Aim Raman spectroscopy of human tissue can provide a unique biochemical 'fingerprint' that alters with disease progression. Light incident on tissue is scattered and may be altered in wavelength, which can be represented as a Raman spectrum. A confocal fibreoptic Raman probe designed to fit down the accessory channel of a colonoscope has been constructed. This in-vitro study evaluated the accuracy of pathological diagnosis in the colon using probe-based Raman spectroscopy. Method Biopsy samples were collected at colonoscopy, snap frozen and stored at −80°C. Raman spectra with 10-s and 1-s acquisition periods were measured with the probe tip in contact with the mucosal surface of thawed specimens. Mathematical modelling using principal component analysis followed by linear discriminant analysis was used to correlate Raman spectra with histopathological diagnoses. Results Three-hundred and seventy-five Raman spectra were measured from a total of 356 colon biopsies (81 of normal colon mucosa, 79 of hyperplastic polyps, 92 of adenomatous polyps, 64 of adenocarcinoma and 40 of ulcerative colitis) from 177 patients. Spectral classification accuracies comparing pathology pairs ranged from 72.1 to 95.9% for 10-s acquisitions and from 61.5 to 95.1% for 1-s acquisitions. For a three-group model of normal, adenomatous and adenocarcinoma tissue, accuracies were 74.1% for 10-s acquisitions and 63.5% for 1-s acquisitions. Conclusion The confocal Raman probe system can distinguish between different colorectal pathologies. The probe has potential to establish Raman spectroscopy as a clinical tool for instant diagnosis at colonoscopy. [ABSTRACT FROM AUTHOR]

Entrepreneurship offers a viable and proven pathway to economic growth and personal fulfillment. However, the number of individuals engaged in entrepreneurial behaviors remains low. This discrepancy between entrepreneurial attitudes and action underscores the need for programs that foster the development of entrepreneurship in today's youth. We argue that a relational developmental systems approach can help researchers understand and facilitate the development of entrepreneurship. In this study, we triangulate across quantitative and qualitative data from the Young Entrepreneurs Study, showing that self-regulation skills, financial risk tolerance, innovation orientation, and the presence of entrepreneurial adults may be especially important for promoting entrepreneurial intent in older adolescents and young adults. We discuss limitations of the present data set and future directions for research. [ABSTRACT FROM AUTHOR]

The pigtail macaque ( Macaca nemestrina) is a common model for the study of AIDS. The pigtail major histocompatibility complex class I allele Mane-A* 10 restricts an immunodominant simian immunodeficiency virus (SIV) Gag epitope (KP9) which rapidly mutates to escape T cell recognition following acute simian/human immunodeficiency virus infection. Two technologies for the detection of Mane-A* 10 in outbred pigtail macaques were developed: reference strand-mediated conformational analysis and sequence-specific primer polymerase chain reaction. A Mane-A*10/KP9 tetramer was then developed to quantify CD8+ T lymphocytes primed by multigenic DNA vaccination, which have previously been difficult to detect using standard interferon- γ-based T cell assays. We also demonstrate mutational escape at KP9 following acute SIV infection. Mane-A* 10+ animals have lower set point SIV levels than Mane-A* 10− animals, suggesting a significant fitness cost of escape. These studies pave the way for a more robust understanding of HIV vaccines in pigtail macaques. [ABSTRACT FROM AUTHOR]

The age, or residence time, of water is a fundamental descriptor of catchment hydrology, revealing information about the storage, flow pathways, and source of water in a single integrated measure. While there has been tremendous recent interest in residence time estimation to characterize watersheds, there are relatively few studies that have quantified residence time at the watershed scale, and fewer still that have extended those results beyond single catchments to larger landscape scales. We examined topographic controls on residence time for seven catchments (0.085-62.4 km2) that represent diverse geologic and geomorphic conditions in the western Cascade Mountains of Oregon. Our primary objective was to determine the dominant physical controls on catchment-scale water residence time and specifically test the hypothesis that residence time is related to the size of the basin. Residence times were estimated by simple convolution models that described the transfer of precipitation isotopic composition to the stream network. We found that base flow mean residence times for exponential distributions ranged from 0.8 to 3.3 years. Mean residence time showed no correlation to basin area (r2 < 0.01) but instead was correlated (r2 = 0.91) to catchment terrain indices representing the flow path distance and flow path gradient to the stream network. These results illustrate that landscape organization (i.e., topography) rather than basin area controls catchment-scale transport. Results from this study may provide a framework for describing scale-invariant transport across climatic and geologic conditions, whereby the internal form and structure of the basin defines the first-order control on base flow residence time. [ABSTRACT FROM AUTHOR]

A sample of 384 thyroid cytology specimens prepared by cytospin over a 2.5-year period was classified by original report into inadequate, non-neoplastic and suspicious of neoplasia or worse. This was then compared with subsequent histology. The resulting data showed an inadequacy rate of 33%, a sensitivity of 55%, a specificity of 59%, a positive predictive value of 64% and a negative predictive value of 93%. On review of the cytology, in knowledge of the subsequent histology, the maximum achievable results were determined to have a positive predictive value of 79% and a negative predictive value of 97%. No clinically significant adverse event was detected. [ABSTRACT FROM AUTHOR]

We conducted a detailed study of subsurface flow and water table response coupled with digital terrain analysis (DTA) of surface and subsurface features at the hillslope scale in Panola Mountain Research Watershed (PMRW), Georgia. Subsurface storm flow contributions of macropore and matrix flow in different sections along an artificial trench face were highly variable in terms of timing, peak flow, recession characteristics, and total flow volume. The trench flow characteristics showed linkages with the spatial tensiometer response defining water table development upslope. DTA of the ground surface did not capture the observed spatial patterns of trench flow or tensiometric response. However, bedrock surface topographic indices significantly improved the estimation of spatial variation of flow at the trench. Point-scale tensiometric data were also more highly correlated with the bedrock surface-based indices. These relationships were further assessed for temporal changes throughout a rainstorm. Linkages between the bedrock indices and the trench flow and spatial water table responses improved during the wetter periods of the rainstorm, when the hillslope became more hydrologically connected. Our results clearly demonstrate that in developing a conceptual framework for understanding the mechanisms of runoff generation, local bedrock topography may be highly significant at the hillslope scale in some catchments where the bedrock surface acts as a relatively impermeable boundary. [ABSTRACT FROM AUTHOR]

Focuses on the stable isotope stratigraphy of river- and lake-ice that archives winter hydroclimatic conditions, and how it can potentially be used to identify changing water sources or to provide important insights into ice formation processes and growth rates. How a one-dimensional diffusion model of the liquid boundary layer adjacent to an advancing solid interface has been used without verification to describe non-equilibrium fractionation during congelation ice growth; Objective of this study concerning the validation of the diffusion model; Results suggesting this diffusion model validation and boundary layer thickness determination provide a powerful tool for interpreting the stable isotope stratigraphy of floating ice; Analysis of the composition of snow ice and frazil ice in river and lake cores indicating similarities between these ice forms.

Photodynamic therapy involves the activation of an exogeneously administered, or an endogenously gen-erated, photosensitizer with light to produce localized tissue destruction. It is an attractive, predominantly endosopic technique for the palliation of advanced upper gastrointestinal cancer and the eradication of early neoplastic and pre-neoplastic lesions. The nature of the biological response allowing safe healing and the exploitation of tissue threshold effects mean that adjacent tissue damage can be minimized. This review used a database of 368 papers. The nature of the photosensitizer is critical to the depth of tissue damage and the risk of adjacent tissue damage and stricture formation. The generation of protoporphyrin IX following administration of 5-aminolaevulinic acid has proved useful for the treatment of high-grade dysplasia in Barrett’s oesophagus. A double-blind randomized placebo controlled trial has confirmed that it is a safe and effective method for the ablation of low-grade dysplasia. The treatment of more advanced lesions requires exogeneously administered photo-sensitizers. However, recent data indicate that the neoplastic potential remains in some patients and continued follow-up is necessary. Photodynamic therapy can be used to eradicate early neoplasia and palliate advanced cancer, but caution is required before a definitive cure can be claimed. [ABSTRACT FROM AUTHOR]

Comments on an article by Coleman and Altini (1999) regarding intravascular tumors in intraoral pleomorphic adenomas. Etiology of intravascular tumors; Reproducibility of results in other cases of pleomorphic adenomas.

Thank you for your interest in our study and commentary.[[1]] We applaud your work to improve the adoption of ultrasound for identifying endometriosis preoperatively. 2 Espada M, Leonardi M, Condous G. Lack of preoperative predictors of surgical complications in patients undergoing endometriosis surgery may be due to lack of adequate preoperative imaging. [Extracted from the article]

The article presents a case study about pressure-induced necrotizing sialometaplasia of the parotid gland. Necrotizing sialometaplasia is a benign inflammatory disorder which affects minor salivary glands usually after operations. The article mentions about a case of the disorder with overlying pressure necrosis of the skin and changes with pressure-induced ischaemia in the parotid gland of a 32-year-old white male in a comatose state.

Reconstruction of continental palaeoclimate and palaeohydrology is currently hampered by limited information about isotopic patterns in the modern hydrologic cycle. To remedy this situation and to provide baseline data for other isotope hydrology studies, more than 4800, depth- and width-integrated, stream samples from391 selected sites within the USGS National Stream Quality Accounting Network (NASQAN) and Hydrologic Benchmark Network (HBN) were analyzed for delta18O and delta2H (http://water.usgs.gov/pubs/ofr/ofr00-160/pdf/ofr0 0-160.pdf). Each site was sampled bimonthly or quarterly for 275 to 3 years between 1984 and 1987. The ability of this dataset to serve as a proxy for the isotopic composition of modern precipitation in the USA is supported by the excellent agreement betweenthe river dataset and the isotopic compositions of adjacent precipitation monitoring sites, the strong spatial coherence of the distributions of delta 18O and delta 2H, the good correlations of the isotopic compositions with climatic parameters, and thegood agreement between the 'national' meteoric water line (MWL) generated from unweighted analyses of samples from the 48 contiguous states of delta 2H=8.11 delta 18O+8.99 (r2=0.98) and the unweighted global MWL of sites from the Global Network for Isotopes in Precipitation (GNIP) of the International Atomic Energy Agency and the World Meteorological Organization (WMO) of delta2H=8.17 delta 18O+10.35. The national MWL is composed of water samples that arise in diverse local conditions wherethe local meteoric water lines (LMWLs) usually have much lower slopes. Adjacent sites often have similar LMWLs, allowing the datasets to be combined into regional MWLs. The slopes of regional MWLs probably reflect the humidity of the local air mass, which imparts a distinctive evaporative isotopic signature to rainfall and hence to stream samples [ABSTRACT FROM AUTHOR]

Nitrate (NO3) and other nutrients discharged by the Mississippi River are suspected of causing a zone of depleted dissolved oxygen (hypoxic zone) in the Gulf of Mexico each summer. The hypoxic zone may have an adverse affect on aquatic life and commercial fisheries. The amount of NO3 delivered by the Mississippi River tothe Gulf of Mexico is well documented, but the relative contributions of different sources of NO3, and the magnitude of subsequent in-stream transformations of NO3, are not well understood. Forty-two water samples collected in 1997 and 1998 at eight stations located either on the Mississippi River or its major tributaries were analyzed for NO3, total nitrogen (N), atrazine, chloride concentrations and NO3 stable isotopes (delta 15N and delta 18O). These data are used to assess themagnitude and nature of in-stream N transformation and to determine if the delta 15N and delta 18O of NO3 provide information about NO3 sources and transformationprocesses in a large river system (drainage area 2 900 000 km2) that would otherwise be unavailable using concentration and discharge data alone. Results from 42 samples indicate that the delta 15N and delta 18O ratios between sites on the Mississippi River and its tributaries are somewhat distinctive, and vary with season and discharge rate. Of particular interest are two nearly Lagrangian sample sets, in which samples from the Mississippi River at St Francisville, LA, are compared with samples collected from the Ohio River at Grand Chain, II, and the Mississippi River at Thebes,IL. In both Lagrangian sets, mass-balance calculations indicate onlya small amount of in-stream N loss. The stable isotope data from thesamples suggest that in-stream N assimilation and not denitrification accounts for most of the N loss in the lower Mississippi River during the [ABSTRACT FROM AUTHOR]

Riverine particulate organic matter (POM) samples were collected bi-weekly to monthly from 40 sites in the Mississippi, Colorado, Rio Grande, and Columbia River Basins (USA) in 1996-97 and analyzed for carbon and nitrogen stable isotopic compositions. These isotopic compositions and C : N ratios were used to identify four endmember sources ofPOM: plankton, fresh terrestrial plant material, aquatic plants, andsoil organic material. This large-scale study also incorporated ancillary chemical and hydrologic data to refine and extend the interpretations of POM sources beyond the source characterizations that could be done solely with isotopic and elemental ratios. The ancillary datawere especially useful for differentiating between seasonal changes in POM source materials and the effects of local nutrient sources andin-stream biogeochemical processes. Average values of delta 13C and C : N for all four river systems suggested that plankton is the dominant source of POM in these rivers, with higher percentagesof plankton downstream of reservoirs. Although the temporal patternsin some rivers are complex, the low delta 13C and C : N values in spring and summer probably indicate plankton blooms, whereasrelatively elevated values in fall and winter are consistent with greater proportions of decaying aquatic vegetation and/or terrestrial material. Seasonal shifts in the delta 13C of POM when the C : N remains relatively constant probably indicate changes in the relative rates of photosynthesis and respiration. Periodic inputs of plant detritus are suggested by C : N ratios >15, principally on the Columbia and Ohio Rivers. The delta 15N and delta 13C also reflect the importance of internal and external sources of dissolved carbon and nitrogen, and the degree of in-stream processing. Elevated delta 15N values at some sites probably reflectinputs from sewage and/or animal waste. This information on the spatial and [ABSTRACT FROM AUTHOR]

Presents correspondence on leiomyoma with atypical cells in the larynx. Comments on the similarity of leiomyoma diagnosis to inflammatory myofibroblastic tumor of the larynx.

Keratinocytes in middle ear cholesteatoma have hyperproliferative properties. There is controversy regarding the role of p53 and its effect on cellular proliferation in cholesteatoma. This study was instituted to examine this. Cholesteatoma and deep meatal skin control specimens were analysed for MIB-1 (n = 7, controls = 7), a marker of cellular proliferation, and p53 (n = 17, controls = 17) expression by immunocytochemistry. Expression of p53 was minimal or absent in both cholesteatoma and controls (P = 0.2). MIB-1 expression was higher, but not significantly so, in cholesteatoma than in controls (P = 0.09). Our study has shown no significant p53 expression in cholesteatoma epithelium. This suggests that there is no dysfunction in the p53-mediated cell cycle control mechanisms in cholesteatoma. [ABSTRACT FROM AUTHOR]

Introduction. There is controversy regarding the expression of p53 and MIB-1 in cholesteatoma.[sup 1] This study was instituted to study this. p53 is an intracellular protein which plays a critical role in control of the cell cycle at the G1 check point. MIB-1 is recognized as a marker of cellular proliferation. Using deep meatal skin controls, the question addressed was, ‘are p52 and MIB-1 overexpressed in cholesteatoma’? Method. Immunocytochemistry using the avidin-biotin technique on frozen tissue sections with primary antibody to p53 (n = 17, controls = 17) and MIB (n = 17, controls = 7) was performed on cholesteatoma and deep meatal skin control specimens. Appropriate positive and negative controls were employed for each antibody. Slides were analysed in a blind fashion by two independent observers. Statistical analysis was performed using the Mann–Whitney test. Results. Expression of p53 was minimal or absent in both cholesteatoma and controls. No significant difference in p53 expression was found between the two groups (P = 0.02). MIB-1 expression was higher in cholesteatoma than in controls, although this was not statistically significant (P = 0.09). Conclusion. This study did not demonstrate an increased expression of p53 cholesteatoma, indicating no evidence of a dysfunctional cell cycle. MIB-1 results showed a possible trend towards significance, which requires a more powerful study to evaluate this further. The probability that there is an increased rate of cellular proliferation in cholesteatoma, when compared to deep meatal skin controls, cannot be excluded. [ABSTRACT FROM AUTHOR]

Aims: Although opioid-related harms have reached new heights across North America, the size of the gap in opioid agonist therapy (OAT) delivery for opioid-related health problems is unknown in most jurisdictions. This study sought to characterize the gap in OAT treatment using a cascade of care framework, and determine factors associated with engagement and retention in treatment., Design: A population-based retrospective cohort study., Setting: Ontario, Canada., Participants: Individuals who sought medical care for opioid-related health problems or died from an opioid-related cause between 2005 and 2019., Measurements: Monthly treatment status for buprenorphine/naloxone or methadone OAT between 2013 and 2019 (i.e. 'off OAT', 'retained on OAT < 6 months', 'retained on OAT ≥ 6 months')., Findings: Of 122 811 individuals in the cohort, 97 516 (79.4%) received OAT at least once during the study period. There was decreasing 6-month treatment retention over time. Model results indicated that males had higher odds of being on OAT each month [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.23-1.28] but lower odds of OAT retention (OR = 0.90, 95% CI = 0.88-0.92), while the reverse was observed for older individuals (monthly: OR = 0.76 per 10-year increase, 95% CI = 0.76-0.77; retention: OR = 1.36 per 10-year increase, 95% CI = 1.34-1.38) and individuals with higher neighbourhood income (e.g. highest income quintile, monthly: OR = 0.79, 95% CI = 0.77-0.82; highest income quintile, retention: OR = 1.15, 95% CI = 1.11-1.20). Individuals residing in rural areas and with a history of mental health diagnoses had poorer outcomes overall, including lower odds of being on OAT each month (rural: OR = 0.75, 95% CI = 0.73-0.78; mental health: OR = 0.89, 95% CI = 0.87-0.92) and OAT retention (rural: OR = 0.79, 95% CI = 0.77-0.82; mental health: OR = 0.81, 95% CI = 0.78-0.83), as well as higher risk of starting/stopping OAT [rural, starting OAT: hazard ratio (HR) = 1.07, 95% CI = 1.05-1.10; mental health, starting OAT: HR = 1.20, 95% CI: 1.18-1.23; rural, stopping OAT: HR = 1.24, 95% CI: = 1.22-1.26; mental health, stopping OAT: HR = 1.11, 95% CI = 1.09-1.13]. Individuals with a history of mental health diagnoses also had a higher risk of death, regardless of OAT status (off OAT death: HR = 1.49, 95% CI = 1.33-1.66; on OAT death: HR = 1.20, 95% CI = 1.09-1.31)., Conclusions: Factors influencing engagement and declining retention in treatment with opioid agonist therapy in Ontario's health system include age, sex and neighbourhood income, as well as mental health diagnoses or residing in rural regions., (© 2022 His Majesty the King in Right of Canada. Addiction © 2022 Society for the Study of Addiction. Reproduced with the permission of the Minister of Health.)

Carbon and nitrogen isotope ratios of human fingernails were measured in 490 individuals in the western US and 273 individuals in southeastern Brazil living in urban areas, and 53 individuals living in a moderately isolated area in the central Amazon region of Brazil and consuming mostly locally grown foods. In addition, we measured the carbon and nitrogen isotope ratios of common food items to assess the extent to which these isotopic signatures remain distinct for people eating both omnivorous and vegetarian diets and living in different parts of the world, and the extent to which dietary information can be interpreted from these analyses. Fingernail delta13C values (mean +/- standard deviation) were -15.4 +/- 1.0 and -18.8 +/- 0.8 per thousand and delta15N values were 10.4 +/- 0.7 and 9.4 +/- 0.6 per thousand for southeastern Brazil and western US populations, respectively. Despite opportunities for a "global supermarket" effect to swamp out carbon and nitrogen isotope ratios in these two urbanized regions of the world, differences in the fingernail isotope ratios between southeastern Brazil and western US populations persisted, and appeared to be more associated with regional agricultural and animal production practices. Omnivores and vegetarians from Brazil and the US were isotopically distinct, both within and between regions. In a comparison of fingernails of individuals from an urban city and isolated communities in the Amazonian region, the urban region was similar to southeastern Brazil, whereas individuals from isolated nonurban communities showed distinctive isotopic values consistent with their diets and with the isotopic values of local foods. Although there is a tendency for a "global supermarket" diet, carbon and nitrogen isotopes of human fingernails hold dietary information directly related to both food sources and dietary practices in a region., (2006 Wiley-Liss, Inc.)

Photodynamic therapy involves the activation of an exogenously administered, or an endogenously generated, photosensitizer with light to produce localized tissue destruction. It is an attractive, predominantly endoscopic technique for the palliation of advanced upper gastrointestinal cancer and the eradication of early neoplastic and pre-neoplastic lesions. The nature of the biological response allowing safe healing and the exploitation of tissue threshold effects mean that adjacent tissue damage can be minimized. This review used a database of 368 papers. The nature of the photosensitizer is critical to the depth of tissue damage and the risk of adjacent tissue damage and stricture formation. The generation of protoporphyrin IX following administration of 5-aminolaevulinic acid has proved useful for the treatment of high-grade dysplasia in Barrett's oesophagus. A double-blind randomized placebo controlled trial has confirmed that it is a safe and effective method for the ablation of low-grade dysplasia. The treatment of more advanced lesions requires exogenously administered photo-sensitizers. However, recent data indicate that the neoplastic potential remains in some patients and continued follow-up is necessary. Photodynamic therapy can be used to eradicate early neoplasia and palliate advanced cancer, but caution is required before a definitive cure can be claimed.