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Studies of plant water sources generally assume that xylem water integrates the isotopic composition (δ 2 H and δ 18 O) of water sources and does not fractionate during uptake or transport along the transpiration pathway. However, woody xerophytes, halophytes, and trees in mesic environments can show isotopic fractionation from source waters. Isotopic fractionation and variation in isotope composition can affect the interpretation of tree water sources, but most studies to date have been greenhouse experiments. Here we present a field-based forensic analysis of xylem water isotope composition for 12 Eucalyptus tetrodonta and Corymbia nesophila trees. We used a 25-tonne excavator to access materials from the trees' maximum rooting depth of 3 m to their highest canopies at 38 m. Substantial within-tree variation occurred in δ 2 H (-91.1‰ to -35.7‰ E. tetrodonta; -88.8‰ to -24.5‰ C. nesophila) and δ 18 O (-12.3‰ to -5.0‰ E. tetrodonta; -10.9‰ to -0.3‰ C. nesophila), with different root-to-branch isotope patterns in each species. Soil water δ 2 H and δ 18 O dual isotope slopes (7.26 E. tetrodonta, 6.66 C. nesophila) were closest to the Local Meteoric Water Line (8.4). The dual isotope slopes of the trees decreased progressively from roots (6.45 E. tetrodonta, 6.07 C. nesophila), to stems (4.61 E. tetrodonta, 5.97 C. nesophila) and branches (4.68 E. tetrodonta, 5.67 C. nesophila), indicative of fractionation along the xylem stream. Roots of both species were more enriched in 2 H and 18 O than soil water at all sampled depths. Bayesian mixing model analysis showed that estimated proportions of water sourced from different depths reflected the contrasting root systems of these species. Our study adds evidence of isotopic fractionation from water uptake and along the transpiration stream in mature trees in monsoonal environments, affecting the interpretation of water sources. We discuss the findings with view of interpreting aboveground xylem water isotopic composition, incorporating knowledge of root systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: There is little information on the prevalence of recreational drug use among UK heterosexual men and women, in particular on use of drugs associated with 'chemsex' within gay communities. The aim of this study was to examine among HIV-negative and HIV-positive heterosexual men and women in England: (i) the prevalence of recreational drug use (including use of drugs associated with chemsex), (ii) socio-economic/lifestyle correlates of drug use, and (iii) the association of drug use with sexual behavior measures and mental health symptoms., Methods: Data are from the AURAH study of HIV-negative individuals attending sexual health clinics across England (2013-2014) and the ASTRA study of HIV-positive individuals attending HIV outpatient clinics in England (2011-2012). Prevalence of recreational drug use (past three months) and associations are presented separately among the four sample groups: HIV-negative (N = 470) and HIV-positive (N = 373) heterosexual men and HIV-negative (N = 676) and HIV-positive (N = 637) women., Results: The age standardized prevalence of any drug use was 22.9%, 17.1%, 15.3%, and 7.1% in the four sample groups respectively. In all groups, cannabis was the drug most commonly used (range from 4.7% to 17.9%) followed by cocaine (1.6% to 8.5%). The prevalence of use of drugs associated with chemsex was very low among HIV-negative participants (1.0% heterosexual men, 0.2% women) and zero among HIV-positive men and women. In age-adjusted analysis, factors linked to drug use overall and/or to cannabis and cocaine use specifically in the four sample groups included Black/mixed Caribbean and white (vs. Black/mixed African) ethnicity, lower level of education , cigarette smoking, and higher risk alcohol consumption. Associations of recreational drug use with measures of condomless sex, depression, and anxiety were observed in the four groups, but were particularly strong/apparent among women., Conclusion: Providers need to be aware of cannabis and cocaine use and its potential link with sexual risk behavior and symptoms of depression and anxiety among heterosexual men and women attending sexual health and HIV clinics., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To compare two methods of monitoring tobacco consumption in remote Indigenous communities., Methods: We examined the monthly difference between wholesale invoice and point-of-sale data for tobacco products from three stores from remote Aboriginal communities in the Northern Territory. We assessed three measures of wholesale data., Results: The average monthly difference between the sale data and the average of wholesale invoices for the previous, same and following month was -33 cigarettes per day (95% CI -157, 92). This average of three months' wholesale invoices provided a more precise estimate than either wholesale invoices from the same or previous month., Conclusion: Tobacco wholesale data provided a close estimate of sales data in these stores., Implications: This wholesale data could be used to monitor local trends in remote Indigenous tobacco consumption, facilitating the evaluation of the impact of tobacco control activities and informing future work to reduce Indigenous smoking and its harms.

The additional value of laparoscopy was investigated with respect to diagnosis and further treatment decisions after abnormal hysterosalpingography (HSG) and prior to intrauterine insemination (IUI). In a retrospective chart review, the number of patients with abnormal HSG who finally need IVF treatment based on the laparoscopic findings was evaluated. Independent of whether HSG showed unilateral or bilateral tubal pathology, IVF was the final treatment decision in only 74 (29%) cases where laparoscopy showed bilateral abnormalities. IUI treatment was advised in 121 (48%) patients with laparoscopically normal findings or unilateral abnormalities. Fifty-seven (23%) patients were treated by IUI after receiving laparoscopic surgery of unilateral adhesions or endometriosis stage 1-2 or after ablation of moderate-severe endometriosis in a second operation. In cases of bilateral tubal abnormalities revealed by HSG, bilateral pathology was confirmed by laparoscopy in at least 58 (46%) patients and they were advised to be treated by IVF after laparoscopy. The agreement between abnormalities found by HSG and abnormalities found by laparoscopy requiring IVF treatment was poor even when HSG showed bilateral pathology. Based on these findings, it is concluded that laparoscopy is mandatory after abnormal HSG findings in the work-up prior to IUI to prevent over-treatment with IVF.

Sarcoidosis is a multisystem disease with cutaneous lesions present in 20%-35% of patients. Given the wide variability of clinical manifestations, it is one of the "great imitators," making it necessary to consider clinical, epidemiological, radiographic, laboratory, and histopathological criteria to make the diagnosis. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of noncaseating granulomas on histologic studies. Specific lesions include maculopapules, plaques, nodules, lupus pernio, scar infiltration, alopecia, ulcerative lesions, and hypopigmentation among others. Nail, mucosal, and childhood sarcoidosis represent a distinct subset of the disease process. The most common nonspecific lesion is erythema nodosum. Others include calcifications, prurigo, erythema multiforme, nail clubbing, and Sweet syndrome. The importance of considering cutaneous sarcoidosis in the clinical differential diagnosis of a given skin lesion relies on the association with systemic involvement and the convenience of the skin as a tissue source for histologic analysis.

This randomized controlled study compared the effectiveness of a gonadotrophin releasing hormone (GnRH) antagonist protocol with or without oral contraceptive (OC) pretreatment on the number of oocytes retrieved in IVF or intracytoplasmic sperm injection (ICSI) patients. Sixty-four patients were randomized to start recombinant human FSH (r-hFSH) on day 2 or 3 after OC withdrawal (OC group) or on day 2 of a natural cycle (control group). From stimulation day 6 onwards, all patients were treated with daily (0.5 mg/ml) GnRH antagonist (Antide). OC pretreatment resulted in significantly lower starting concentrations of FSH, LH and oestradiol (P < 0.001) and a thinner endometrium (P < 0.0001). In the early stimulation period, fewer large follicles were found after OC pretreatment, leading to a significantly extended stimulation period (11.6 versus 8.7 days, P < 0.0001) with more follicles on the day of recombinant human chorionic gonadotrophin administration (15.4 versus 12.5, P = 0.02) and more oocytes retrieved (13.5 versus 10.2, P < 0.001) as compared with the control group. GnRH antagonist regimen, pretreated with OC, prevented the early endogenous FSH rise and improved follicular homogeneity, resulting in more oocytes. As a consequence of the extended treatment period, more rhFSH was required.

With the introduction of new instruments and improved sensor chip chemistries, surface plasmon resonance (SPR) is finding new applications for molecular interaction studies. Easy access to high-quality kinetic and thermodynamic data for macromolecular binding events is providing insights into the fundamental mechanisms of molecular recognition. Progress is being made to allow larger-scale interaction studies. In addition, combining SPR with other analytical methods is enabling SPR-based analysis of interaction proteomics.

Background: Couples affected by idiopathic subfertility or male subfertility have an estimated spontaneous conception rate of about 2% per cycle. Although various infertility treatments are available, counselling of a couple in their choice of treatment is difficult because of the lack of consistent data from good-quality comparative studies. We compared the results of treatment with intrauterine insemination (IUI) with those of in-vitro fertilisation (IVF), and did a cost-effectiveness analysis., Methods: In a prospective, randomised, parallel trial, 258 couples with idiopathic subfertility or male subfertility were treated for a maximum of six cycles of either IUI in the spontaneous cycle (IUI alone), IUI after mild ovarian hyperstimulation, or IVF. The primary endpoint was a pregnancy resulting in at least one livebirth after treatment. Cost-effectiveness based on real costs was studied by Markov chain analysis., Findings: 86 couples were assigned IUI alone, 85 IUI plus ovarian hyperstimulation, and 87 IVF. Ten couples dropped out before treatment began. Although the pregnancy rate per cycle was higher in the IVF group than in the IUI groups (12.2% vs 7.4% and 8.7%, respectively; p=0.09), the cumulative pregnancy rate for IVF was not significantly better than that for IUI. Couples in the IVF group were more likely than those in the IUI groups to give up treatment before their maximum of six attempts (37 [42%] drop-outs vs 13 [15%] and 14 [16%], respectively; p<0.01). The woman's age was the only factor that influenced a couple's chance of success. IUI was a more cost-effective treatment than IVF (costs per pregnancy resulting in at least one livebirth 8423-10661 Dutch guilders [US$4511-5710] for IUI vs 27409 Dutch guilders [US$14679] for IVF)., Interpretation: Couples with idiopathic or male subfertility should be counselled that IUI offers the same likelihood of successful pregnancy as IVF, and is a more cost-effective approach. IUI in the spontaneous cycle carries fewer health risks than does IUI after mild hormonal stimulation and is therefore the first-choice treatment.

A biologically active construct of the retroviral M domain from the avian Rous sarcoma virus is defined and its solution structure described. This M domain is fully active in budding and infectivity without myristylation. In spite of a sequence homology level that suggests no relationship among M domains and the family of matrix proteins in mammalian retroviruses, the conserved structural elements of a central core allow an M domain sequence motif to be described for all retroviruses. The surface of the M domain has a highly clustered positive patch comprised of sequentially distant residues. An analysis of the backbone dynamics, incorporating rotational anisotropy, is used to estimate the thermodynamics of proposed domain oligomerization., (Copyright 1998 Academic Press Limited.)

Purpose: Corneal curvature can be altered by shrinking stromal collagen with a pulsed solid-state holmium: YAG laser in a procedure termed laser thermokeratoplasty., Methods: The authors performed laser thermokeratoplasty in 40 human cadaver eyes using a ring pattern of 32 spots, each spot having a diameter of 300 microns., Results: The amount of induced corneal steepening decreased as ring diameter was increased in 1 mm increments, with 22.2 +/- 3.3 and 3.7 +/- 2.0 diopters (D) of central steepening with diameters of 3 and 7 mm, respectively. Results of histologic examination showed a cone-shaped zone of increased stromal hematoxylin uptake extending posteriorly for 90% of stromal thickness. Energy levels greater than those needed to induce topographic changes produced limited endothelial injury in rabbit corneas and, in some cases, intraocular inflammation. A computerized, finite element model of the globe demonstrated central corneal steepening as a result of heat-induced stromal contraction to a depth of 75% corneal thickness., Conclusions: These data support previous studies indicating that central corneal topography can be modified by heating corneal stroma in a controlled fashion with the mid-infrared holmium:YAG laser.

Ten patients with large melanomas and one patient with recurrent retinoblastoma were treated with combined localized current field (LCF) hyperthermia and iodine 125 irradiation delivered by episcleral plaque. Tumors were heated to 43 degrees to 45 degrees C for 28 to 45 minutes. Localized current field hyperthermia when combined with irradiation appeared to induce rapid tumor necrosis. One eye enucleated 17 hours after treatment showed only focal necrosis of the melanoma, while another eye demonstrated extensive necrosis 60 hours after treatment. In all remaining eyes, tumor regression occurred within the first month of treatment. Complications included cataract formation in six eyes, hemorrhagic retinal detachment in five eyes, and phthisis in two eyes. Complications from combined therapy of large intraocular tumors in this series appeared to result from the rapid necrosis of the tumor and secondary intraocular inflammation. Intraocular temperature dosimetry measurements demonstrated a temperature gradient of not more than -0.23 degrees C/mm-1 per axial millimeter from the episcleral plaque surface to the apex of the tumor. The authors believe that LCF hyperthermia could be a suitable means of application of hyperthermia in patients with intraocular tumors if further modifications were performed to reduce ocular complications.

HMB-45 is a monoclonal antibody recently described as being highly specific for melanocytic proliferations of the skin and in metastases of melanotic lesions. To determine a possible role for HMB-45 in ophthalmic pathology, 45 conjunctival lesions, including 23 melanomas, were analyzed using immunohistochemical techniques with anti-S-100 and HMB-45 as primary antibodies. Nineteen (82.6%) of the melanomas exhibited HMB-45 positivity, and 19 (82.6%) contained S-100 protein, with concordance of all but two cases. Seven cases of primary acquired melanosis were studied; one (33%) of three with atypia was HMB-45 positive, as were two (50%) of four without atypia. Among nevi, 1 (9.1%) of 11 showed faint staining with HMB-45. Fifteen conjunctival epithelial dysplasias were negative with HMB-45. At present, HMB-45 appears to offer no great advantage over S-100 protein in the analysis of conjunctival melanomas. Its role in the distinction of benign from atypical or malignant junctional melanocytic proliferations remains unclear.

A study was made of the Arthus reaction in an animal model of Hageman-factor deficiency, namely Hageman trait cats, and in control cats with normal Hageman-factor activity. At three time points, there was a significant decrease (P less than 0.01) in the size of the cutaneous Arthus reaction to chicken red blood cells in biopsies from Hageman trait cats compared with the reaction in biopsies from control animals. Injection of a positive control, histamine, and a negative control, phosphate-buffered saline, produced no significant differences between the two groups. Hageman trait cats had a significant decrease (P less than 0.001) in the number of neutrophils in the skin lesions compared with controls. When Hageman trait cats were injected intravenously with purified cat Hageman factor, Arthus reactions were similar to those observed in control cats.

Seventy-one conjunctival melanocytic proliferations in patients 20 years of age or younger were examined. Sixty-five (91.5%) were nevi; there were three cases (4.2%) of racial or acquired melanosis, and three patients were identified who had malignant melanoma of the conjunctiva. The melanoma patients are presented in detail, and additional cases of conjunctival melanoma in children and adolescents reported in the literature are reviewed to determine factors that might influence prognosis. The number of cases is so small, however, that factors cannot be identified with confidence. Follow-up data are presented. Conjunctival nevi are relatively common in children, and appear to carry no risk for the development of melanoma during childhood. However, -conjunctival melanomas do occur rarely in children and have a variable prognosis.

Following administration of aspartame (34 mg/kg body wt) in orange juice, plasma concentrations of free amino acids were measured in 12 female subjects known to be heterozygous for phenylketonuria and 22 normal subjects (12 male, 10 female). No change in fasting plasma aspartate concentrations were noted after aspartame loading in either group. In normal male subjects, the mean (+/-S.D.) plasma phenylalanine concentration increased from a fasting value of 5.86 +/- 1.25 mumol/dl. Plasma phenylalanine levels in normal female subjects increased from a mean fasting concentration of 4.83 +/- 0.84 mumol/dl to a men peak value of 8.95 +/- 1.49 mumol/dl suggesting a more rapid absorption, metabolism, and/or clearance of phenylalanine by females. In female heterozygous subjects, the mean peak plasma phenylalanine concentration was significantly higher than in normal females. Plasma phenylalanine values increased from a mean fasting value of 5.92 +/- 1.51 mumol/dl to a mean peak value of 15.1 +/- 4.76 mumol/dl. Similarly, the area under the plasma phenylalanine concentration-time curve was significantly greater in heterozygous female subjects (21.36 +/- 5.10 IU) than in normal female subjects (10.84 +/- 2.32 IU). However, peak plasma phenylalanine levels were well below those associated with toxic effects in all cases.

Plasma and erythrocyte levels of free amino acids were measured in five female subjects known to be heterozygous for phenylketonuria and six subjects assumed to be normal (three male, three female) who were administered an abuse dose of aspartame (100 mg/kg) in orange juice. Small increases in plasma aspartate levels were noted 30 minutes after aspartame loading in both groups, with mean (+/- SD) levels increasing from 0.15 +/- 0.05 mumoles/100 ml to 0.43 +/- 0.23 mumoles/100 ml in normal subjects (P = 0.02), and from 0.49 +/- 0.23 mumoles/100 ml to 0.80 +/- 0.56 mumoles/100 ml in heterozygous subjects (P > 0.05). However, plasma aspartate levels remained within normal postprandial levels in each case. Erythrocyte aspartate levels were unchanged in both groups. In normal subjects, plasma phenylalanine levels (mean +/- SD) increased from fasting levels (5.40 +/- 1.05 mumoles/100 ml) to mean peak values of 20.2 +/- 6.77 mumoles/100 ml. In heterozygous subjects, mean peak plasma phenylalanine levels were approximately twice as high (41.7 +/- 2.33 mumoles/100 ml), and the area under the plasma concentration-time curve twice as large. Peak plasma phenylalanine levels, however, were below those associated with toxic effects. The data indicate slower, but adequate metabolism and clearance of an abuse dose of aspartame by the phenylketonuric heterozygote.

A high-speed liquid chromatographic method for analysis of sulfasalazine (salicylazosulfapyridine) in bulk powder and tablet dosage form is presented. Analysis is accomplished with a reverse-phase partition column and 10% 2-propanol in pH 7.7 phosphate buffer as the mobile phase. The method of analysis utilizes a simple, one-step, solubilization procedure with dimethylformamide, addition of an internal standard, and chromatography. The method is specific for sulfasalazine in the presence of starting materials, degradation products, or by-products from its manufacture.

A case of mucopolysaccharidosis, Type II-A (Hunter syndrome, severe) is described, with emphasis on ocular ultrastructural findings. Single membrane-bound structures containing fibrillogranular and, less commonly, multi-membranous material were found in conjunctival epithelium, pericytes and fibrocytes; corneal epithelium, keratocytes, and endothelium; trabecular endothelium; iris pigmented epithelium, smooth muscle, and fibrocytes; ciliary pigmented and nonpigmented epithelium and fibrocytes; retinal pigment epithelium and ganglion cells; optic nerve astrocytes and pericytes; and sclerocytes. The most striking accumulation was in the nonpigmented ciliary epithelium. These findings are compared with those seen in MPS II-B, and in other systemic mucopolysaccharidoses. The nature and distribution of inclusions are not specific to any one disorder, but help to signal the presence of one of the storage disorders. Distension of corneal keratocytes may play a role in the corneal clouding seen in some of these disorders. The importance of tissue examination, especially conjunctival biopsy, in the diagnosis of storage disorders and in assessment of future modes of therapy for the mucopolysaccharidoses is discussed.

Autopsy findings of 133 patients who died following fungemia or with invasive fungal infection were reviewed. Common clinical factors included antibiotic therapy, chemotherapy, corticosteroid administration, hyperalimentation, malignancy, and bone marrow transplantation. Fungal infection was seldom diagnosed antemortem and fungemia was detected in only 24 patients (18%). Ocular involvement occurred in 14 patients (Candida 11, Aspergillus 2, and Cryptococcus 1). The eye was the fifth most commonly involved organ at autopsy among patients with candida infection. Ocular involvement occurred with a significantly greater frequency in patients with Candida tropicalis than with Candida albicans infections (P less than 0.05). Although only about 10% of patients with fungal infections had ocular involvement, all those with ocular lesions had widely disseminated disease. Realizing the potential toxicity of antifungal therapy, we recommend that screening ophthalmologic examinations be performed on patients with fungemia or patients at high risk for development of fungal infection. The presence of ocular lesions consistent with fungal disease, in the appropriate setting, is a strong indication for investigation of possible systemic fungal infection and therapy once a definitive diagnosis is established.