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Introduction: Across the United Kingdom (UK), National Health Service (NHS) orthodontic treatment is commissioned differently across the devolved nations. There is a relative paucity in the literature describing the way in which the orthodontic services in each country are commissioned and treatment outcomes measured., Objective: To highlight the differences in the following: commissioning of primary care orthodontic services across the UK; assessment of treatment outcomes; and the potential impacts these differences have on contractors, performers and patient care., Materials and Methods: Data were collected using an online mixed-methods approach. Systematic content analysis was used to extract the required information from the websites and guidance documents of orthodontic service providers, which was then catalogued and verified electronically by senior dental advisors in the four devolved UK nations., Results: The Index of Orthodontic Treatment Need (IOTN) is a mandatory needs assessment tool used across all four nations, with an agreed minimum threshold of a dental health component (DHC) score of 3 and an aesthetic component (AC) score of 6 for NHS treatment. While the peer assessment rating (PAR) is the most utilised method of assessing post-treatment outcomes, it is applied differently by each country., Conclusion: While NHS orthodontic services across the UK share mutual elements of service delivery, there are significant differences in the prior approval process and assessment of treatment outcomes. More research is required to assess the economic feasibility of orthodontic treatment from the associated treatment outcomes.

An analytical method was developed for the determination of morpholine on apples and citrus. The method utilized acidified methanol extraction, centrifugation, and determination by hydrophilic interaction liquid chromatography with electrospray ionization and tandem mass spectrometry (HILIC-ESI-MS/MS). Validation of the method occurred at the Pacific Agricultural Laboratory (PAL, Portland, OR, USA) and the Trace Analytical Laboratory (TAL, UC Davis, CA, USA). Method validation recoveries from control apple, orange, lemon, and grapefruit samples ranged from 84 to 120% over three levels of fortification (0.01, 0.04, and 0.2 μg/g). The limit of quantitation (LOQ) for all commodities was 0.01 μg/g, and the calculated method detection limit (MDL) ranged from 0.0010 to 0.0040 μg/g.

Protein S-prenylation is a lipid modification that regulates membrane-protein and protein-protein interactions in cell signaling. Though sites of protein S-prenylation can be predicted based upon conserved C-terminal CaaX or CC/CXC motifs, biochemical detection of protein S-prenylation in cells is still challenging. Herein, we report an alkynyl-isoprenol chemical reporter (alk-FOH) as an efficient substrate for prenyltransferases in mammalian cells that enables sensitive detection of S-farnesylated and S-geranylgeranylated proteins using bioorthogonal ligation methods. Fluorescent detection alleviates the need to deplete cellular isoprenoids for biochemical analysis of S-prenylated proteins and enables robust characterization of S-prenylated proteins, such as effectors that are injected into host cells by bacterial pathogens. This alkynyl-prenylation reporter provides a sensitive tool for biochemical analysis and rapid profiling of prenylated proteins in cells.

Linguists have traditionally represented patterns of divergence within a language family in terms of either a 'splits' model, corresponding to a branching family tree structure, or the wave model, resulting in a (dialect) continuum. Recent phylogenetic analyses, however, have tended to assume the former as a viable idealization also for the latter. But the contrast matters, for it typically reflects different processes in the real world: speaker populations either separated by migrations, or expanding over continuous territory. Since history often leaves a complex of both patterns within the same language family, ideally we need a single model to capture both, and tease apart the respective contributions of each. The 'network' type of phylogenetic method offers this, so we review recent applications to language data. Most have used lexical data, encoded as binary or multi-state characters. We look instead at continuous distance measures of divergence in phonetics. Our output networks combine branch- and continuum-like signals in ways that correspond well to known histories (illustrated for Germanic, and particularly English). We thus challenge the traditional insistence on shared innovations, setting out a new, principled explanation for why complex language histories can emerge correctly from distance measures, despite shared retentions and parallel innovations.

An expansion of structure-activity studies on a series of substituted 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine PDE4 inhibitors and the introduction of a related [1,2,4]triazolo[4,3-b]pyridazine based inhibitor of PDE4 is presented. The development of SAR included strategic incorporation of known substituents on the critical catachol diether moiety of the 6-phenyl appendage on each heterocyclic core. From these studies, (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (10) and (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine (18) were identified as highly potent PDE4A inhibitors. Each of these analogues was submitted across a panel of 21 PDE family members and was shown to be highly selective for PDE4 isoforms (PDE4A, PDE4B, PDE4C, PDE4D). Both 10 and 18 were then evaluated in divergent cell-based assays to assess their relevant use as probes of PDE4 activity. Finally, docking studies with selective ligands (including 10 and 18) were undertaken to better understand this chemotypes ability to bind and inhibit PDE4 selectively.

Objective: This study was undertaken to document physical injuries and ascertain associated variables in female complainants of sexual assault., Study Design: 164 cases of sexual assault between 2002 and 2006 in Belfast were included. 162 women consented to body examination and 153 to genital examination. Data for the study were obtained from the contemporaneous notes of a forensic doctor who examined the victims., Results: Of 164 females, 44% were less than 20 years of age, mean age was 24.2, range 13-74 years; two-thirds reported alcohol consumption prior to assault. Non-genital (body) injury was observed in 61%, genital injury in 39%, both in 20% and 18% had no injury. Body injury was associated with time to examination (OR=4.0, p<0.01), alcohol intake prior to assault (OR=3.33, p<0.001), assault occurring outdoors (OR=3.45, p<0.01), previous sexual intercourse (OR=3.19, p<0.01) and genital injury (OR=2.24, p<0.05). Genital injury was related to acquaintance assault (OR=2.33, p<0.05), time to examination (OR=3.70, p<0.05), reported virgin status (OR=3.03, p<0.01) and absence of hormonal contraception (OR=2.04, p<0.10)., Conclusion: Almost half the victims of sexual assault were less than 20 years old and injury was detected in over 80%. Time to examination and prior sexual experience were related to genital and body injury. Assault occurring outdoors and alcohol intake were associated with body injury. Genital injury was more frequent in acquaintance assault and victims not using hormonal contraception. Young females drinking alcohol are at a very high risk for sexual assault.

Rationale and Objectives: This study was conducted to determine whether significant reduction in radiation dose (250 mAs-->50 mAs), in chest computed tomography (CT) using volume acquisition affects image quality or the detectability of pathologic findings in the lung and mediastinum., Methods: Phantom studies were conducted to evaluate resolution and noise level, then a patient study was then done. Fifty consecutive patients (10 normal and 40 abnormal) cases were examined. After a scan (250 mAs, 120OkVp) of the entire thorax, five additional slices (50 mAs, 120kVp) at the level of the abnormality were obtained. Three independent observers evaluated the visibility of normal lung and mediastinal structures, as well as image noise. The mean score was compared between the standard and low doses. In a second study, an independent evaluation of the presence or absence of pathologic findings was made by four observers., Results: Lucite phantom studies demonstrated diminished low-contrast resolution and increased noise level for the low-dose technique. Observers assessed more noise in the low-dose images (P < 0.001). The normal structures were judged to be more visible with standard dose (P < 0.01), but the magnitude of the judged differences was small especially in the lung. No differences were found in the detection of lung and mediastinal abnormalities (P > 0.10)., Conclusions: The low-dose technique was effective in demonstrating pathologic findings for the lung and mediastinum. Low-dose spiral CT should be considered as a viable alternative to standard-dose spiral CT.

Purpose: To evaluate the accuracy of CT angiography of occlusive disease of the carotid arteries using three-dimensional surface-rendered images alone and in conjunction with display of axial source images., Methods: Forty-eight symptomatic patients had conventional angiography followed by CT angiography within 24 hours. Images of 96 carotid arteries were acquired using contrast-enhanced spiral CT. Image postprocessing was performed on a free-standing workstation to produce 3-D shaded surface display (SSD) images. Two readers independently evaluated the CT angiographic (SSD) images and then reevaluated each case while simultaneously reviewing the SSD and axial source images. Digital subtraction angiograms were evaluated in a separate session and eventually compared with CT angiograms. All evaluations were performed under blinded conditions to control for reader bias., Results: SSD images alone underestimated stenosis relative to angiograms whereas combined SSD and axial images did not., Conclusion: SSD angiograms in conjunction with the source images are better than SSD images alone in estimating the degree of stenosis in carotid artery disease.

A model that derives multiple-observer decision strategy ROC curves for boolean decision rules applied to binary decisions of two or three observers is presented. It is assumed that covert decision variables consistent with ROC models of observer performance underlie decisions and that readers' decision criteria are in a fixed relationship. The specific parameters of individual ROC curves and the correlational structure that describes interobserver agreement have dramatic effects upon the relative benefits to be derived from different boolean strategies. A common strategy employed in clinical practice, in which the overall decision is positive if any observer makes a positive decision, is most effective when the readers are of similar ability, when they adopt similar decision criteria, when interreader agreement is greater for negative than for positive cases, and when the individual ROC slope is <<1.0. Different multiple-observer decision strategies can be evaluated using the model equations. A bootstrap method for testing model-associated hypotheses is described.

Purpose: To determine the usefulness of CT angiography in the setting of suspected acute subarachnoid hemorrhage or intracranial aneurysm., Methods: We prospectively studied 68 patients suspected of having subarachnoid hemorrhage or an intracranial aneurysm with noncontrast CT of the head followed immediately by contrast-enhanced helical CT of the circle of Willis with three-dimensional reconstruction. Twenty-seven patients with CT findings positive for subarachnoid hemorrhage or intracranial aneurysm were evaluated with digital subtraction angiography or MR angiography within 12 hours of CT angiography. Patients with negative CT/CT angiography findings were followed up with lumbar puncture., Results: CT angiography showed 23 of 24 aneurysms and 2 of 2 arteriovenous malformations (sensitivity, 96%; specificity, 100%). Aneurysm size ranged from 2 to 40 mm (mean, 7.9 mm). Interobserver variability was 10%. In the 23 cases of subarachnoid hemorrhage, cisternal blood did not limit the three-dimensional reconstruction. Two patients with aneurysms on CT angiography had normal noncontrast scans., Conclusions: CT angiography of the circle of Willis is a useful technique for evaluation of suspected acute subarachnoid hemorrhage and intracranial aneurysm. It provides anatomic display of intracranial aneurysms, allowing for planning of conventional angiography and surgical approach. In selected cases, CT angiography may eliminate the need for preoperative conventional angiography.

Objective: The purpose of this investigation was to assess the utility of allowing free adjustment of window width and level in comparison with the use of a fixed lung window in the CT evaluation of diffuse lung disease., Materials and Methods: Six radiologists each judged 36 cases (28 diffuse lung disease and 8 normal) using a standardized form. In half of the sessions, images were viewed in a fixed lung window (level = -500 HU; width = 2,000 HU). In the other sessions, the observer was able to adjust the window and level freely while viewing the images. Each case was seen twice in separate sessions: once in a fixed lung window and once with window width and level adjusted by the reader. A variety of diagnostic features were evaluated using a 5 point scale. These included visibility of fine lung structures, abnormalities of the lung parenchyma, and overall evaluation of the lung., Results: The visibility of lung structures was not improved with adjustable window settings. Receiver operating characteristic (ROC) analysis showed fixed windows to be superior to adjustable windows for overall evaluation of the cases [fixed A(z) = 0.90, adjustable A(z) = 0.84, p < 0.05, jackknife method]. Time to rate each case was increased by 15% with window width and level adjustment., Conclusion: Free adjustment of window width and level produced no improvement in reader performance over that achieved with fixed window width and level.

Emergency physicians can expect to see more patients with malignancies. Some of these malignancies can lead to life-threatening emergencies, and the emergency physician must suspect and be able to recognize these problems.

Three methods of breathing retraining (guided breathing retraining, guided breathing retraining with physiologic monitoring of thoracic and abdominal movement plus peripheral temperature, and guided breathing retraining with physiologic monitoring of thoracic and abdominal movement, peripheral temperature and end-tidal carbon dioxide) were compared with a no-treatment control group to determine the effectiveness of breathing retraining on modifying respiratory physiology and reducing functional cardiac symptoms in subjects with signs associated with hyperventilation syndrome. Of 41 subjects studied, 16 were diagnosed with mitral valve prolapse. Results demonstrated that all 3 methods of breathing retraining were equally effective in modifying respiratory physiology and reducing the frequency of functional cardiac symptoms. Results determined that respiratory rate and subject's perception that training had generalized were the best predictors of treatment success. Furthermore, it was found that subjects with mitral valve prolapse responded as well to treatment as did those without prolapse.

A case of profound digital vasoconstriction caused by the accidental injection of epinephrine from a commercial bee sting kit is reported. One hour later the patient had a cold, painful, blanched finger. A digital block using a 2-mg dose of phentolamine mixed with 2% lidocaine was performed. Thirty minutes after treatment, the finger was pink and warm. The patient reported a marked decrease in pain. Reexamination 12 hours later showed only mild tenderness at the fingertip. No tissue necrosis occurred. One month after injection, there were no apparent sequelae. Although the use of alpha-adrenergic blocking agents by regional infiltration to treat accidental infusion or extravasation of epinephrine has been suggested, no reports of this technique are found in the emergency medicine literature. The mechanism of digital vasoconstriction and the action of phentolamine are discussed.

Two experiments investigated the properties of visual persistence as functions of spatial frequency, stimulus duration, and pattern-specific adaptation. In Experiment 1, increasing the duration of high spatial-frequency gratings from 50 to 500 msec decreased the duration of visual persistence produced by that grating to an asymptotic level. However, low-frequency gratings produced a constant estimate of visual persistence independent of presentation time. Also, spatial-frequency specific adaptation reduced the persistence of the high-frequency gratings to this asymptotic level, but the lower frequency persistence estimates already at this level were unaffected (Experiment 2). These findings are related to possible temporal properties of the sustained and transient visual systems.

After viewing red vertical stripes and green horizontal stripes, the eye subsequently views white vertical stripes as greenish and white horizontal stripes as pinkish. It has been theorized that this phenomenon, known as the McCollough effect, is related to long-tern adaptation of cells tuned for both color and orientation. Such cells have been found in the visual cortex of the rhesus monkey. We asked whether rhesus monkeys, like man, experience a McCollough effect. Two humans and two rhesus monkeys were adapted by requiring them to fixate a spot moving slowly across alternating horizontal and vertical gratings of complementary color. Following adaptation, a test grating whose color changed from red to green or green to red was presented. Humans and monkeys were instructed or trained to release a response lever during the interval that the grating was white. After adaptation, there were orientation-specific changes in all four subjects' responses as would be predicted if both man and monkey were experiencing a McCollough effect.

Nine subjects with obstructive airway disease took part in this double-blind study of the effect of glucagon in relieving bronchoconstriction compared with isoproterenol or isotonic saline. Drugs were administered via an in-line intermittent positive-pressure breathing unit. FEV1, MEF, PEF, and nitrogen washout data were evaluated. Ten minutes after administration of saline, mean FEV1 and MEF values were significantly reduced from baseline levels (P less than 0.05). Compared to saline, isoproterenol was followed by significantly increased FEV1 and MEF values (P less than 0.05) at both 10 and 30 minutes after medication, indicating reduction in bronchoconstriction. Although the 1-mg dose of glucagon was followed by a mean decrease in these parameters, this decrease was less than that seen after saline alone.

Lidocaine is a widely used antiarrhythmic agent whose plasma clearance varies with changes in hepatic blood flow. Cimetidine, an H2-receptor antagonist, has been shown to decrease hepatic blood flow. To ascertain whether cimetidine affected serum lidocaine concentration, we studied 21 patients receiving lidocaine infusions and divided them into two groups. Fifteen patients received cimetidine, 300 mg every 6 hours, in addition to lidocaine; six patients received only lidocaine. In 14 of the 15 patients receiving both lidocaine and cimetidine, a rise in serum lidocaine levels was seen, whereas no change was noted in the control group. Six of the 15 patients were found to have levels in the toxic range and two had symptoms. An additional three patients on lidocaine received diphenhydramine, an H1-receptor antagonist. No elevation in serum lidocaine levels was noted after administration of diphenhydramine. We conclude that there exists an interaction between lidocaine and cimetidine and that the rise in serum lidocaine levels may be mediated by cimetidine's inhibition of the H2 receptor.

Measurements were made of urinary tryptophan metabolites of 13 tuberculosis patients in order to reveal characteristics of pyridoxine-dependent metabolism before and during cycloserine treatment. The abnormally high level of xanthurenic acid excretion in untreated patients suggests a decreased availability of pyridoxal phosphate related to the disease process. Although plasma cycloserine levels were kept high once therapy began, xanthurenic acid excretion before and after tryptophan load became progressively more normal as symptoms diminished. This observation suggests that the convulsions which may sometimes accompany cycloserine administration are not due to a direct pyridoxine antagonism by the drug. Throughout the study, no significant changes in 5-hydroxyindoleacetic acid excretion were observed. Presumably, the metabolic pathway of serotonin is unaffected by tryptophan loading, cycloserine administration, or the apparent pyridoxine depletion associated with tuberculosis.

Twenty-six patients (19 men and 7 women) with symptomatic ventricular tachycardia (VT) were studied using invasive and noninvasive techniques to induce VT. Of the study population, 12% had syncope and VT on Holter monitoring, 30% had cardiac arrest and 58% had symptomatic VT. All patients had antiarrhythmic agents stopped 5 half-lives before evaluation and then had autonomic profile (upright tilt, cold pressor test, exercise testing and hand grip) as well as programmed electrical stimulation studies performed. Autonomic profile testing induced VT in 5 of 26 patients (19%) and in only 1 patient was the arrhythmia reproducibly induced. All 26 patients had VT induced on electrophysiologic testing; 9 patients had nonsustained and 17 had sustained VT. Lorcainide administered intravenously prevented VT induction in 20 of 26 patients tested, whereas procainamide was effective in 11 of 24 patients. Ten of the 13 not protected by procainamide were protected by lorcainide. Twenty patients were started on long-term lorcainide therapy and followed up for 29 +/- 3.4 months. Five patients have discontinued therapy, 2 because of breakthrough arrhythmias, 2 because of severe sleep-wake disturbances and 1 because of private physician preference. An additional 3 patients died during therapy because of myocardial infarction in 1, progressive myopathy in 1 and sudden death in 1. Sixty percent of patients started on lorcainide therapy have continued. In this patient population, noninvasive induction of VT is not a sensitive or reproducible technique in assessing antiarrhythmic therapy. Furthermore, when selected on the basis of electrophysiologic testing, lorcainide is a well-tolerated and effective antiarrhythmic agent.

The authors have mapped visuotopic organization of prelunate gyrus and adjacent buried cortex in the rhesus monkey. They found two orderly representations of the lower, contralateral visual quadrant in this cortex.

We have examined topographic organization of the prelunate gyrus and adjacent cortex buried in the lunate and superior temporal sulci. We recorded from cortex of awake rhesus monkeys performing a fixation task. Multiunit receptive fields were mapped with small, stationary spots of light to determine borders and points of strongest driving or "activity centers" of the fields. We found evidence for several distinct subdivisions of this cortex. A representation of the vertical meridian runs across the gyrus, and two crude topographic representations of the central 30 degrees of the lower quadrant, the posteromedial and anterolateral areas (area PM and area AL), share this representation of the meridian. Area AL extends from the prelunate gyrus into the posterior bank of the superior temporal sulcus; it is separated from the MT area by a narrow strip of cortex. Area PM occupies part of the prelunate gyrus and extends into the anterior bank of the lunate sulcus. Receptive field size in both AL and PM is an increasing function of eccentricity and is similar for the two areas. Medial to areas PM and AL on the prelunate gyrus is another cortical region with qualitatively different topographic organization.

An atlas of high resolution infrared emission spectra identifies a number of gaseous atmospheric features significant to stratospheric chemistry in the 770-900- and 1100-1360-cm(-1) regions at six zenith angles from 86.7 to 95.1 degrees . A balloon-borne Michelson interferometer was flown to obtain ~0.03-cm(-1) resolution spectra. Two 10-cm-1 extracts are presented here.

Lidoflazine is a calcium channel blocking agent that is effective and safe in the treatment of angina pectoris, but has been reported to be associated with sudden death when administered for the treatment of supraventricular arrhythmias. Studies were performed in dogs to determine if lidoflazine caused a rise in serum digoxin concentration that could cause arrhythmias or if it was directly arrhythmogenic. Dogs received chronic injections of digoxin and then digoxin in combination with lidoflazine. No increase in digoxin concentration was found. Dogs also underwent programmed electrical stimulation while not receiving medications and then after incremental doses of lidoflazine administered intravenously. Lidoflazine did not cause spontaneous ventricular tachycardia and did not lower the threshold of ventricular tachycardia induction. Combined administration of lidoflazine and digoxin did not facilitate arrhythmia induction. These studies do not support a digoxin-lidoflazine interaction or a direct arrhythmogenic action of lidoflazine.

The perceived duration of a photopically illuminated, fixated grating presented for 50 milliseconds increased (from 300 to 500 milliseconds) with spatial frequency (0.9 to 15 cycles per degree). This suggests a sustained neural channel contribution to short-term visual storage, and argues against a pure photoreceptor, especially a rod, locus for such storage.

Motion aftereffects, typically found to result only from localized retinal stimulation, were obtained within regions of the visual field that had not been stimulated by moving contours. "Phantom" stripes are seen moving through a physically homogeneous (empty) region of the visual field when vertical stripes move above and below that region. Immediately afterward, stationary stripes in the previously empty region appear to move in the opposite direction. This phantom-motion aftereffect provides a novel instance of the way global structure affects processes that have been assumed to be influenced only by simpler local spatial and temporal variables.