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The Teton anticline and adjacent structures, in the Sawtooth Range, Montana, USA, are fractured in such a way that may be taken as a model for fractures propagating during buckle folding. However, advances in understanding both the process of folding in forelands and the evolution of fracture patterns found within these folds suggest that it is time to reinterpret the nexus between fracturing and folding within these classic structures. With the benefit of seismic lines, the Teton anticline is best described as a fault-propagation fold. Joint propagation initiated with the formation of two major sets whose orientation is controlled by pre-folding, regional stresses. Two more joint sets propagated in local stress fields, developed in response to anticline growth. Some early joints were reactivated as wrench faults during amplification and tightening of the anticlines. The fracture sets identified are consistent with: (a) propagation in a regional stress field, which may be related to stretching in the Sawtooth Range orocline; and (b) tangential longitudinal strain of the backlimb and forcing or trishear of the forelimb during anticline development. Thus, we suggest that fracture networks across folded structures should be interpreted and characterized in the light of the geological history of the entire system.

In this work we highlight the importance of radiative convection as a mixing mechanism in a large, ice‐free lake (Lake Michigan, USA), where solar heating of waters below the temperature of maximum density drives vertical convection during the vernal turnover. Measurements taken over a 2‐week period at a 55‐m deep site demonstrate the ability of radiative convection to mix the entire water column. Observations show a diurnal cycle in which solar heating drives a steady deepening of the convective mixed layer throughout the day (dHCML/dt= 12.8 m/hr), followed by surface‐cooling‐induced restratification during the night. Radiative convection is linked to a dramatic enhancement in turbulence characteristics, including both turbulent kinetic energy dissipation (ϵ: 10−9–10−7W/kg) and turbulent scalar diffusivity (Kz: 10−3–10−1m2/s), suggesting that radiative convection plays a major role in driving vertical mixing throughout the water column during the isothermalspring. When freshwater lakes fall below the temperature of maximum density (TMD≈4 °C), solar‐driven radiative convection can become a major source of turbulent mixing. As the sun heats near‐surface waters, the denser (warmer) waters sink rapidly throughout the water column, driving increased mixing and vertical transport. In the current paper, we highlight the importance of this mixing mechanism as observed during a 2‐week experiment at a 55‐m deep site in a large, ice‐free lake (Lake Michigan, USA). Observations demonstrate a daily cycle in which solar heating drives energetic, full water column mixing throughout the day, followed by significant surface cooling and restratification overnight. We show that radiative convection is linked to dramatic enhancements in turbulence characteristics. This suggests that convection plays a major role in setting spring mixing conditions throughout the Laurentian Great Lakes, with important implications for both biological and chemical species. This work represents one of the first observations of radiative convection in an ice‐free lake, providing important insight for other large midlatitude lakes. Radiative convection drives strong, deep mixing during the vernal turnover in a large, ice‐free lake (Lake Michigan)Temperature profiles show a diurnal cycle of full water column mixing each day followed by surface‐cooled restratification overnightRadiative convection is linked to a multiple‐order enhancement in turbulence characteristics, including both dissipation and diffusivity

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen’s d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case–control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen’s d=−0.232; P=3.50 × 10−7) and thalamus (d=−0.148; P=4.27 × 10−3) and enlarged lateral ventricles (d=−0.260; P=3.93 × 10−5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen’s d=−0.46), amygdala (d=−0.31), thalamus (d=−0.31), accumbens (d=−0.25) and intracranial volumes (d=−0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.

This editorial discusses the application of a novel brain imaging analysis technique in the assessment of neuroanatomical dysconnectivity in psychotic illnesses. There has long been a clinical interest in psychosis as a disconnection syndrome. In recent years graph theory metrics have been applied to functional and structural imaging datasets to derive measures of brain connectivity, which represent the efficiency of brain networks. These metrics can be derived from structural neuroimaging datasets acquired using diffusion imaging whereby cortical structures are parcellated into nodes and white matter tracts represent edges connecting these nodes. Furthermore neuroanatomical measures of connectivity may be decoupled from measures of physiological connectivity as assessed using functional imaging, underpinning the need for multi-modal imaging approaches to probe brain networks. Studies to date have reported a number of structural brain connectivity abnormalities associated with schizophrenia that carry potential as illness biomarkers. Structural connectivity abnormalities have also been reported in well patients with bipolar disorder and in unaffected relatives of patients with schizophrenia. Such connectivity metrics may represent clinically relevant biomarkers in studies employing a longitudinal design of illness course in psychosis.

Abstract: Imperfections in glass formed during manufacture or subsequent transportation can weaken bottles, creating a hazard by causing them to fail at lower pressure. When soda glass bottles are pressurized to fracture, the crack density in the broken glass and the fracture pressure are highly correlated. A higher fracture pressure yields a higher crack density as a result of the greater amount of stored energy released on fracture. Thus, after failure it is possible to estimate the pressure to which a bottle was subjected by analyzing the glass fragments. The crack patterns and density agree with analytical models for crack branching in brittle materials under stress. The crack patterns of pressurized bottles subjected to impact are also observed, and a minimum side impact velocity of 2.0 m/s for rupture of pressurized commercial soda glass bottles is determined.

Understanding the influence of molecular environment on phospholipids is important in time-of-flight secondary ion mass spectrometry (TOF-SIMS) studies of complex systems such as cellular membranes. Varying the molecular environment of model membrane Langmuir−Blodgett (LB) films is shown to affect the TOF-SIMS signal of the phospholipids in the films. The molecular environment of a LB film of dipalmitoylphosphatidylcholine (DPPC) is changed by varying the film density, varying the sample substrate, and the addition of cholesterol. An increase in film density results in a decrease in the headgroup fragment ion signal at a mass-to-charge ratio of 184 (phosphocholine). Varying the sample substrate increases the secondary ion yield of phosphocholine as does the addition of proton-donating molecules such as cholesterol to the DPPC LB film. Switching from a model system of DPPC and cholesterol to one of dipalmitoylphosphatidylethanolamine (DPPE) and cholesterol demonstrates the ability of cholesterol to also mask the phospholipid headgroup ion signal. TOF-SIMS studies of simplistic phospholipid LB model membrane systems demonstrate the potential use of these systems in TOF-SIMS analysis of cells.

DUFFEY, M. J., D. F. MARTIN, D. W. CANNON, T. CRAVEN, and S. P. MESSIER. Etiologic factors associated with anterior knee pain in distance runners. Med. Sci. Sports Exerc.,Vol. 32, No. 11, pp. 1825–1832, 2000.

delta-Opioid receptors have been implicated in reinforcement processes and antagonists are available that produce long-lasting and selective antagonism of delta-opioid receptors in vivo. This experiment assessed the contribution of delta-opioid receptors to the antinociceptive and reinforcing properties of heroin. The effects of the irreversible delta-antagonist naltrindole-5'-isothiocyanate (5'-NTII) were evaluated on heroin self-administration and hot-plate antinociception in rats. 5'-NTII (10 nmol i.c.v.) shifted the dose-response curve for heroin self-administration downward, increasing the A(50) values on the ascending and descending limbs by approximately 0.5 log units and decreasing the maximum by 33%. 5'-NTII (40 nmol i.c.v.) shifted both limbs of the heroin self-administration dose-effect curve 1.2 log units to the right and decreased the maximum by 90%. Heroin self-administration gradually returned to baseline levels over 7 or 17 days after administration of 10 or 40 nmol 5'-NTII, respectively. 5'-NTII (40 nmol i.c.v.) decreased the self-administration of 0.17 mg/infusion cocaine by 40% while having no effect on responding maintained by 0.33 or 0.67 mg/infusion. 5'-NTII attenuated the antinociceptive effects of deltorphin (delta(2)) in a dose-dependent manner while having no effect on antinociception elicited after i.c. v. administration of [D-Pen(2),D-Pen(5)]-enkephalin (delta(1)) or [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (mu). In addition, the antinociceptive effects of heroin were not significantly affected by 5'-NTII (40 nmol i.c.v.). Therefore, 5'-NTII can attenuate the reinforcing effects of heroin at doses that do not affect its antinociceptive effects. Long-acting delta(2)-opioid antagonists may be beneficial in the treatment of heroin dependence or as adjuncts to reduce the abuse liability of opioid analgesics.

Four different isomers of 2',3'-dideoxy-3'-thiacytidine [beta-DL-(+-)-BCH-189] were evaluated in primary human lymphocytes infected with human immunodeficiency virus type 1. The beta-L-(-) isomer was the most potent enantiomer, with a median effective concentration of 1.8 nM and no discernible cytotoxicity up to 100 microM. The relative order of potencies for the isomers was beta-L-(-) greater than beta-DL-(+-) racemic greater than beta-D-(+) greater than alpha-L-(+) greater than alpha-D-(-). The beta-L-(-) enantiomer was as potent as 3'-azido-3'-deoxythymidine.

The relative antiviral potencies of five nucleotide heterodimers of 3'-azido-3'-deoxythymidine (AZT), 3'-azido-3'-deoxythymidilyl-(5',5')-2'-3'-dideoxy-5'-adenylic acid (AZT-P-ddA), 3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-dideoxy-5'-inosinic acid (AZT-P-ddI), and the corresponding 2-cyanoethyl congeners AZT-P(CyE)-ddA and AZT-P(CyE)-ddI, were determined in primary human peripheral blood mononuclear cells infected with human immunodeficiency virus type 1. The homodimer 3'-azido-3'-deoxythymidilyl-(5',5')-3'-azido-3'-deoxythymidilic acid (AZT-P-AZT) was also included for comparison. The potencies of the compounds were AZT-P-ddA greater than or equal to AZT-P-ddI greater than AZT-P(CyE)-ddA greater than or equal to AZT-P(CyE)-ddI greater than or equal to AZT greater than AZT-P-AZT. Whereas AZT-P-ddA and AZT-P-ddI had in vitro therapeutic indices greater than that of AZT, the homodimer of AZT had a low therapeutic index. AZT-P-ddI exhibited the lowest toxicity in peripheral blood mononuclear, Vero, or CEM cells. Combination studies between AZT and 2',3'-dideoxyinosine (ddI) at nontoxic concentrations indicated a synergistic interaction at a drug ratio of 1:100. At higher ratios (1:500 and 1:1,000), the interactions were synergistic only at concentrations that produced up to 75% virus inhibition. At higher levels of antiviral effects, this combination was antagonistic, as determined by the multiple drug effect analysis method. AZT-P-ddI was about 10-fold less toxic than AZT to human granulocyte-macrophage progenitor cells. However, no significant difference was apparent when the compounds were evaluated against cells of the erythroid lineage. The greater antiviral activity and lower toxicity of this compound could not be attributed to the extracellular decomposition of the dimer in media at physiological temperature and pH. However, in acidic solutions, AZT-P-ddI decomposed in a pH-dependent manner. Advanced preclinical studies with this heterodimer of two clinically effective antiretroviral agents should be considered.

Patients who volunteered for a controlled drinking training program had more severe alcohol problems and less social and family stability than those who opted for abstinence-oriented programs.

The standing crop of benthic and planktonic algae in the Moruya River, Australia, was, in general, low compared with values given for northern hemisphere rivers. Diatoms always accounted for more than 90% of the algae on the sediments with the most common species being typical of holarctic flora. The relative abundance of each of six predominant taxa was similar at the three sampling localities and did not show marked seasonal variation. However, Gomphonemaspp. contributed a relatively greater number in the downstream area whereas Cocconeis placentulaEhr. was comparatively more abundant upstream. The highest standing crop (1.47 × 106cells/cm2) was found downstream and in the calmest part of the river between January and March, coincident with maximum water temperatures. A true phytoplankton succession comprising filamentous chlorophytes, Scenedesmus, Melosira variansAg., Dactylococcopsis, Eudorinaand Merismopediawas observed at the most downstream site during the spring and summer, with a maximum standing crop of 126.7 × 103cells/litre being attained in December. The gut of larval lampreys > 100 mm contained large numbers (44,000–525,000 cells) of algae. Scenedesmusand Dactylococcopsisoccurred much more frequently in the gut than in either the sediment or water, but the reverse was true for filamentous algae.

This article describes a general experimental technique to infer the potential advantages of proposed, unrealized improvements to a working system. The technique models a complex system as a function of the subsystems improved by the proposals. It emphasizes systems with components that are difficult to model, such as human operators. The inferred-advantage method explores the model of the present system by systematically restricting the performance of the system's subcomponents as if they are experimental control variables and then assessing the benefit of a proposed improvement by extrapolation. The article describes the application of the technique to an advanced telerobotic system, provides a general experimental procedure to apply the technique, and validates this procedure on a simulated design problem. The inferred-advantage technique provides experimental validation for design proposals before managers must commit resources to detail design and hardware investments.

Abstract: This paper describes an interactive system for specifying robotic tasks using virtual tools that allow an operator to reach into a live video scene and direct robots to use corresponding real tools in complex scenarios that involve integrating a variety of otherwise autonomous technologies. The attribute rich virtual tools concept provides a human-machine interface that is robust to unanticipated developments and tunable to the specific requirements of a particular task. This Interactive Specification concept is applied to intermediate manufacturing tasks.

2',3'-Dideoxy-5-fluoro-3'-thiacytidine (FTC) has been shown to be a potent and selective compound against human immunodeficiency virus type 1 in acutely infected primary human lymphocytes. FTC is also active against human immunodeficiency virus type 2, simian immunodeficiency virus, and feline immunodeficiency virus in various cell culture systems, including human monocytes. The antiviral activity can be prevented by 2'-deoxycytidine, but not by other natural nucleosides, suggesting that FTC must be phosphorylated to be active and 2'-deoxycytidine kinase is responsible for the phosphorylation. By using chiral columns or enzymatic techniques, the two enantiomers of FTC were separated. The (-)-beta-enantiomer of FTC was about 20-fold more potent than the (+)-beta-enantiomer against human immunodeficiency virus type 1 in peripheral blood mononuclear cells and was also effective in thymidine kinase-deficient CEM cells. Racemic FTC and its enantiomers were nontoxic to human lymphocytes and other cell lines at concentrations of up to 100 microM. Studies with human bone marrow cells indicated that racemic FTC and its (-)-enantiomer had a median inhibitory concentration of > 30 microM. The (+)-enantiomer was significantly more toxic than the (-)-enantiomer to myeloid progenitor cells. The susceptibilities to FTC of pretherapy isolates in comparison with those of posttherapy 3'-azido-3'-deoxythymidine-resistant viruses in human lymphocytes were not substantially different. Similar results were obtained with well-defined 2',3'-dideoxyinosine- and nevirapine-resistant viruses. (-)-FTC-5'-triphosphate competitively inhibited human immunodeficiency virus type 1 reverse transcriptase, with an inhibition constant of 2.9 microM, when a poly(I)n.oligo(dC)19-24 template primer was used. These results suggest that further development of the (-)-Beta-enantiomer of FTC is warranted as an antiviral agent for infections caused by human immunodeficiency viruses.

The objectives of our study were: 1) to examine differences between a noninjured cohort of runners (N= 70) and runners afflicted with iliotibial band friction syndrome (ITBFS) (N= 56) according to selected anthropometric, biomechanical, muscular strength, and training measures; 2) to explore multivariate relationships among these measures in both the well and injured groups; and 3) to develop specific hypotheses concerning risk factors for injury that will later be tested in a prospective observational study. High speed videography (200 fps), a force platform (500 Hz), and a Cybex II+isokinetic dynamometer were used to assess rearfoot motion, ground reaction forces, and knee muscular strength and endurance, respectively. A linear discriminant function analysis of the training data revealed weekly mileage, training pace, number of months using current training protocol, time spent swimming, and time spent running on a track to be significant (P< 0.10). Height was a significant anthropometric discriminator, while seven isokinetic strength and endurance measures were found to discriminate significantly between the groups. Calcaneal to vertical touchdown angle, and maximum supination velocity were significant rearfoot movement discriminators. Maximum braking force was the only significant kinetic discriminator. A combined discriminant analysis using those variables found to be significant in the previous analyses revealed weekly mileage, and maximum normalized braking force to be the best discriminators (model P< 0.05). Our results suggest that there are several variables that discriminate between noninjured runners and runners afflicted with ITBFS.

This Technical Note outlines some of the work undertaken by British Rail Research (BRR) on the viability of joining together existing bolted rail to create continuously welded rail.

Summary Embolus radiolabelling with131I fibrinogen was studied in a canine model of internal carotid artery embolization. The dog was chosen as the experimental animal because of its maxillocarotid artery which permits collateral flow round the occlusion and helps to prevent strokes. Clot was prepared by incubating blood at room temperature to inactivate plasminogen activators and then refrigerating it to promote clot retraction. Emboli persisting 48 hours were seen in 80% of animals. Major strokes were not seen when 0.25 to 0.30 cm3 were used. Autoradiography and well counting revealed uptake of isotope. The test, when refined, should provide a tool for the investigation of thromboemboli.

Since clinical trials are being planned with the immunomodulating drug isoprinosine combined with the antiviral drug 3'-azido-3'-deoxythymidine (AZT) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex, it is important to determine the type of antiviral interaction produced by these drugs in vitro. Such a combined modality may not only produce enhanced antiviral effects but also may have a valuable immunorestorative action. The interaction of several ratios of AZT and isoprinosine on the replication of human immunodeficiency virus type 1 in human peripheral blood mononuclear cells was determined by reverse transcriptase assay of disrupted virus obtained from supernatants of cells that were exposed to virus and the drugs separately and in combination and by a human immunodeficiency virus type 1 p24 enzyme immunoassay of the same supernatants. The correlation between the reverse transcriptase and enzyme immunoassay data was high. The antiviral activity of AZT alone was neither diminished nor augmented when AZT was used in combination with isoprinosine. Isoprinosine did not enhance virus yield when used alone or in combination with AZT in peripheral blood mononuclear cells, nor did it affect the growth of uninfected cells. The in vitro results indicate that this combination did not decrease the efficacy of AZT or exacerbate virus replication.

Summary While endogenous immunoreactive substance P (SP) is relatively stable in human plasma in vitro and gives the same radioimmunoassay results after several weeks of cold storage, added synthetic exogenous substance P can be only partially recovered from fresh plasma and disappears from it rapidly.

When an alternating voltage is applied to a colloid, the particles move back and forth at a velocity that depends on their size and zeta potential and on the frequency of the applied field. As they move, the particles generate sound waves. In this paper we describe a new device for measuring this electroacoustic effect. From this measurement the frequency-dependent electrophoretic mobility (or "dynamic" mobility) of the particles can be determined in suspensions of arbitrary concentration, and from the dynamic mobility spectrum it is possible to obtain the size distribution and the zeta potential of the particles. The great advantage of the technique is that it is not limited to dilute suspensions. After describing the operating principles and calibration of the device, we present mobility spectra obtained on model silica suspension. It is found that these spectra are in good agreement with O'Brien's thin double layer formula, down to a κa value of 20. We then show how size distribution and zeta potential can be obtained from the mobility spectrum, and we compare results for a number of suspensions with measurements made using other techniques. Copyright 1995, 1999 Academic Press

The (-) enantiomers of 2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC] and 2',3'-dideoxy-3'-thiacytidine [(-)-BCH-189] were recently shown to inhibit selectively human immunodeficiency viruses (HIV) and hepatitis B virus in vitro. In the current study, the potential for HIV type 1 (HIV-1) resistance to these compounds was evaluated by serial passage of the virus in human peripheral blood mononuclear cells and MT-2 cells in the presence of increasing drug concentrations. Highly drug-resistant HIV-1 variants dominated the replicating virus population after two or more cycles of infection. The resistant variants were cross-resistant to (-)-FTC, (-)-BCH-189, and their (+) congeners but remained susceptible to 2',3'-dideoxycytidine, 3'-azido-3'-deoxythymidine, 3'-fluoro-3'-deoxythymidine, 2',3'-dideoxyinosine, phosphonoformate, the TIBO compound R82150, and the bis(heteroaryl)piperazine derivative U-87201E. Reverse transcriptase derived from drug-resistant viral particles was 15- to 50-fold less susceptible to the 5'-triphosphates of FTC and BCH-189 compared with enzyme from parental drug-susceptible virus. DNA sequence analysis of the reverse transcriptase gene amplified from resistant viruses consistently identified mutations at codon 184 from Met (ATG) to Val (GTG or GTA) or Ile (ATA). Sequence analysis of amplified reverse transcriptase from a patient who had received (-)-BCH-189 therapy for 4 months demonstrated a mixture of the Met-184-to-Val (GTG) mutation and the parental genotype, indicating that the Met-184 mutation can occur in vivo.

The special purpose of my paper is to remove the weeds which arrest the growth and development of the modern theories of dysmenorrhœa which I outlined in a previous communication. Some of these weeds are most difficult to eradicate; for they have their roots deep down in the history of gynæcology. I refer in particular to Menge’s version of the psychological theory of pain which he based upon a false philosophy and a false physiology. I admit that a genuine psychological theory of dysmenorrhœa based upon Aristotle’s theory of body-mind relationship is a theoretical possibility. We shall have to depend, however, upon the results of psychotherapy in order to refute the hypothesis or convert it into an accepted theory. I also admit that psychological factors may augment the intensity of dysmenorrhœic pain. Psychotherapy, therefore, may be a useful adjunct to the treatment of dysmenorrhœic cases whether they rest upon a physiological or psychological basis. Mechanical theories of dysmenorrhœa arise from a natural prejudice on the part of certain gynæcologists against psychological explanations; for between such explanations of functional dysmenorrhœa and mechanical explanations, there can be no via media from the point of view of psycho-physical parallelism.

Part 1 of the European Rails Standard, concerning flat-bottom symmetrical railway rails, is being developed by Working Group 4 of the CEN Railway Applications Techntcal Committee TC 256. Its probable requirements for quality assurance and inspection, steel manufacture and grades, qualifying tests, and the new or modified acceptance tests, are outlined. Attempts are being made to introduce many performance-related aspects.

Pulmonary lymphangitic carcinomatosis is an unusual presentation of diffuse infiltrative lung disease. In this report, we present a case secondary to cervical carcinoma that has been previously reported in only four patients. The diagnosis was made by transbronchial lung biopsy.

AbstractAimsTo identify and synthesise the literature on the cost of mental disorders.MethodsSystematic literature searches were conducted in the databases PubMed, EMBASE, Web of Science, EconLit, NHS York Database and PsychInfo using key terms for cost and mental disorders. Searches were restricted to January 1980–May 2019. The inclusion criteria were: (1) cost-of-illness studies or cost-analyses; (2) diagnosis of at least one mental disorder; (3) study population based on the general population; (4) outcome in monetary units. The systematic review was preregistered on PROSPERO (ID: CRD42019127783).ResultsIn total, 13 579 potential titles and abstracts were screened and 439 full-text articles were evaluated by two independent reviewers. Of these, 112 articles were included from the systematic searches and 31 additional articles from snowball searching, resulting in 143 included articles. Data were available from 48 countries and categorised according to nine mental disorder groups. The quality of the studies varied widely and there was a lack of studies from low- and middle-income countries and for certain types of mental disorders (e.g. intellectual disabilities and eating disorders). Our study showed that certain groups of mental disorders are more costly than others and that these rankings are relatively stable between countries. An interactive data visualisation site can be found here: https://nbepi.com/econ.ConclusionsThis is the first study to provide a comprehensive overview of the cost of mental disorders worldwide.

THE crack opening displacement (COD) test is currently being used by a large number of research establishments throughout Britain and the USA to establish the fracture characteristics of high toughness–low strength steels.

Correction to: Molecular Psychiatry (2015); advance online publication 2 June 2015; doi:10.1038/mp.2015.63 Following publication of the above article, the authors noticed that the forty-third author’s last name was presented incorrectly. The author’s name should have been listed as HE Hulshoff Pol. The publisher regrets the error.

High levels of substance P-like immunoreactivity were demonstrated by radioimmunoassay in the plasma and tumour of a patient with a medullary carcinoma of the thyroid.

The subfractions Fa, Fb, and Fc of crude substance P (SP) preparations made from human and bovine brains were analysed for SP and the COOH-terminal octapeptide of cholecystokinin (CCK-8). The methods were specific radioimmunoassays (RIAs) for SP and CCK-8, and bioassays on isolated organs of the guinea pig: the ileum, the gallbladder and the field-stimulated vas deferens.1.In bioassays of synthetic peptides the vas deferens reacted specifically to SP and the gallbladder to CCK-8.2.RIAs and bioassays revealed unequivocally that most of SP-like activity was present in Fb, while Fc contained mainly CCK-8-like activity. Varying results were obtained with Fa.3.The pharmacologically active principle of Fc is CCK-8 or a closely related peptide. Earlier results concerning the pharmacological and neurochemical properties of Fc must be ascribed to this peptide.

Elevated glycosylated haemoglobin values have been observed in overtly diabetic animals from a colony of spontaneously diabetic rabbits. Chemically diabetic and normal animals did not show elevated levels. Overtly diabetic animals averaged 12.2% glycosylated haemoglobin versus 4.3% for chemically diabetic and 3.9% for normal animals. Increased levels did not correlate with plasma glucose concentration. Some chemically diabetic and normal animals progressed with time to a more severe diabetic classification. Glycosylated haemoglobin levels at the high end of the range of values for normal animals are predictive of this progression especially in certain litters.