Unveiling the Enhancement of Spontaneous Emission at Exceptional Points.

Exceptional points (EPs), singularities of non-Hermitian physics where complex spectral resonances degenerate, are one of the most exotic features of nonequilibrium open systems with unique properties. For instance, the emission rate of quantum emitters placed near resonators with EPs is enhanced (compared to the free-space emission rate) by a factor that scales quadratically with the resonance quality factor. Here, we verify the theory of spontaneous emission at EPs by measuring photoluminescence from photonic-crystal slabs that are embedded with a high-quantum-yield active material. While our experimental results verify the theoretically predicted enhancement, they also highlight the practical limitations on the enhancement due to material loss. Our designed structures can be used in applications that require enhanced and controlled emission, such as quantum sensing and imaging.

Surgical interventions in adult upper limb spasticity management: a systematic review.

Upper limb spasticity following upper motor neuron lesion is a key cause of long-term disability in adults, causing functional loss, pain, and reduced quality of life. Surgical management is an under-utilized intervention, and little work has been performed to collate and evaluate the evidence for these interventions. We undertake the first, PRISMA-compliant systematic review synthesizing the evidence for surgical management of spasticity in adults. Three databases were searched using pre-specified search strings over a 20-year window (September 2001-2021). Only primary research papers featuring an entirely adult sample were included. Case reports were excluded. Quality assessment was performed using the Oxford Centre for Evidence-Based Medicine Scale and the Methodological Index for Non-Randomized Studies. We identified 19 eligible studies, all of which were poor quality. Significant benefit of surgery was identified in 15 of the 16 studies conducting significance testing. Detailed analysis of the surgical procedures used was prevented by poor reporting. Studies reported low rates of serious postoperative complication, and relatively high rates of postoperative deformity recurrence. Studies' approaches to patient assessment and management varied significantly, reflecting a lack of standardization in this field. This review suggests that higher-quality, more standardized evidence is required to demonstrate the safety and efficacy of these surgical procedures. Future work should focus on improved reporting of surgical procedures and development of consensus assessment tools focusing on assessment of patient functionality and quality of life.

Recruitment of patients into head and neck clinical trials: acceptability of studies to patients from perspective of the research team.

We reviewed longitudinal recruitment data to assess recruitment into head and neck cancer trials, and to identify factors that could influence this and affect their acceptability to patients. We retrieved data from the prospective computerised database (2009-2016) to measure acceptability to patients using the recruitment:screening ratio, and compared observational with interventional studies, single specialty (or site) with multispecialty (or site) studies, and "step-up" randomisation with "non-inferiority" randomisation designs. A total of 1283 patients were screened and 583 recruited. The recruitment:screening ratio for all National Institute for Health Research (NIHR) portfolio studies combined was 0.47 (486/1133). Studies that involved treatment by several specialties or at several sites had a significantly adverse impact on acceptability (p=0.01). Recruitment into non-inferiority randomised controlled studies was lower than that into step-up randomised studies (p=0.06). The complexity of a study's design did not compromise recruitment. Treatment across several specialties or several sites and perceived non-inferiority designs, reduced the acceptability of some trials.

Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.

Mutations in the gene for the transcription factor hepatocyte nuclear factor (HNF) 1alpha cause maturity-onset diabetes of the young (MODY) 3, a form of diabetes that results from defects in insulin secretion. Since the nature of these defects has not been defined, we compared insulin secretory function in heterozygous [HNF-1alpha (+/-)] or homozygous [HNF-1alpha (-/-)] mice with null mutations in the HNF-1alpha gene with their wild-type littermates [HNF-1alpha (+/+)]. Blood glucose concentrations were similar in HNF-1alpha (+/+) and (+/-) mice (7.8+/-0.2 and 7.9+/-0.3 mM), but were significantly higher in the HNF-1alpha (-/-) mice (13.1+/-0.7 mM, P < 0.001). Insulin secretory responses to glucose and arginine in the perfused pancreas and perifused islets from HNF-1alpha (-/-) mice were < 15% of the values in the other two groups and were associated with similar reductions in intracellular Ca2+ responses. These defects were not due to a decrease in glucokinase or insulin gene transcription. beta cell mass adjusted for body weight was not reduced in the (-/-) animals, although pancreatic insulin content adjusted for pancreas weight was slightly lower (0.06+/-0.01 vs. 0.10+/-0.01 microg/mg, P < 0.01) than in the (+/+) animals. In summary, a null mutation in the HNF-1alpha gene in homozygous mice leads to diabetes due to alterations in the pathways that regulate beta cell responses to secretagogues including glucose and arginine. These results provide further evidence in support of a key role for HNF-1alpha in the maintenance of normal beta cell function.

Increased beta-cell proliferation and reduced mass before diabetes onset in the nonobese diabetic mouse.

To determine whether loss of beta-cell mass and function in the NOD mouse occurs gradually, beginning after the onset of insulitis, or abruptly, just before the onset of overt diabetes, beta-cell mass and rates of beta-cell proliferation and insulin secretory responses from the perfused pancreas were measured in NOD and control NOD/Scid mice at 8-9, 13, and 18 weeks of age. Of the NOD mice, 11 and 70% had diabetes (fasting blood glucose >8.3 mmol/l) at 13 and 18 weeks of age, respectively. Beta-cell mass in 8-week-old NOD mice was 69% of control mice (P>0.05), but the rate of 5-bromo-2-deoxyuridine uptake was greater, suggesting a compensatory proliferative response to ongoing autoimmune beta-cell destruction. Despite an increase in the rate of beta-cell proliferation, beta-cell mass was significantly reduced by 42% in 13-week-old nondiabetic NOD mice and by 73% in 18-week-old diabetic NOD mice. Insulin secretory responses to glucose and arginine demonstrated reductions of similar magnitude. In 18-week-old diabetic NOD mice, insulin secretion was reduced to a greater degree than beta-cell mass, suggesting the presence of beta-cell dysfunction in addition to reduced mass. These results suggest that in the NOD mouse, beta-cell destruction begins soon after the onset of insulitis. Despite a compensatory beta-cell proliferative response, beta-cell mass progressively falls and is significantly reduced by 13 weeks despite normal blood glucose concentrations. Diabetes may be present when residual beta-cell mass represents 30% of control levels.

Role of apoptosis in failure of beta-cell mass compensation for insulin resistance and beta-cell defects in the male Zucker diabetic fatty rat.

To define the mechanisms involved in the evolution of diabetes in the Zucker diabetic fatty (ZDF) rat, beta-cell mass and replication rates were determined by immunochemistry, point-counting morphometry, and 6-h 5-bromo-2'-deoxyuridine (BrdU) incorporation. The beta-cell mass in 5- to 7-week-old prediabetic ZDF rats (4.3 +/- 0.06 mg) was similar to age-matched insulin-resistant Zucker fatty (ZF) rats (3.7 +/- 0.05 mg) and greater than that in Zucker lean control (ZLC) rats (1.9 +/- 0.3, P < 0.05). At 12 weeks (after diabetes onset), beta-cell mass in the ZDF rats (8.1 +/- 1.7 mg) was significantly lower than the ZF rats (15.7 +/- 1.8 mg). The mass in the ZF rats was significantly greater than in the ZLC rats (4.3 +/- 0.8 mg, P < 0.05). The beta-cell proliferation rate (mean of both time points) was significantly greater in the ZDF rats (0.88 +/- 0.1%) compared with the ZF and ZLC rats (0.53 +/- 0.07%, 0.62 +/- 0.07%, respectively, P < 0.05), yet ZDF rats have a lower beta-cell mass than the ZF rats despite a higher proliferative rate. Morphological evidence of neogenesis and apoptosis is evident in the ZF and ZDF rats. In addition, even at 5-7 weeks a modest defect in insulin secretion per beta-cell unit was found by pancreas perfusion. These studies provide evidence that the expansion of beta-cell mass in response to insulin resistance and insulin secretory defects in diabetic ZDF rats is inadequate. This failure of beta-cell mass expansion in the ZDF rat does not appear to be from a reduction in the rate of beta-cell proliferation or neogenesis, suggesting an increased rate of cell death by apoptosis.

Immunological response to immunotherapy for immediate hypersensitivity: clinical relevance.

Immunotherapy, also called desensitization, is effective in treating allergic rhinitis, insect sting venom hypersensitivity and probably allergic asthma. Administration of gradually increasing doses of the sensitizing antigen induces several immunological changes. The humoral responses include an increase in specific IgG titer, a decrease in specific IgE titer with blunting of its seasonal rise, and an increase in the specific anti-idiotype antibody titer. Cellular changes include diminished responsiveness of the patient's lymphocytes to stimulation by allergen as measured by thymidine incorporation. This is accounted for by the generation of suppressor cells specific for the allergen. These suppressor cells also induce suppression of IgE production by mononuclear cells. An additional effect that is attributed to IT is a decrease in basophil sensitivity to the allergen as measured by histamine release. The clinical correlates of these changes are not clear. Currently, none of the responses can be used as a tool for assessing the response in the treated individual patient. Although the increase in specific IgG was shown to correlate with the clinical response in patient groups, it is not applicable to the individual patient. Currently the best parameter for assessing clinical response is probably the increase in the ratio between the specific IgG and the specific IgE. However further studies are warranted to evaluate the significance of the change in anti-idiotype antibodies, basophil histamine release and perhaps immunological changes yet to be discovered.

Chromatography tubes: a novel RIA technique.

We describe a novel radioimmunoassay in which separation of free and antibody-bound antigen is achieved by passive means. The separation is carried out by a modified form of inverted dry column chromatography on a column, or 'chromatography tube', consisting of a small polystyrene tube packed with a dry, insoluble, hydrophilic resin. Using the radioimmunoassay or digoxin as an example, an exceptionally simple procedure is described with sensitivity, accuracy and precision suitable for clinical purposes. Advantages of the chromatography tube method are discussed.

Serum immunoglobulin levels in patients with active pulmonary tuberculosis and patients with Klebsiella infection.

Serum immunoglobulins levels were determined in 42 patients with active pulmonary tuberculosis as a prototype of chronic infection and 41 patients with Klebsiella infection representing acute infection, using a radial immunodiffusion technique. The mean serum concentration of IgG, IgA and IgM of the patients with pulmonary tuberculosis (1980 +/- 688, 314 +/- 152 and 222 +/- 123 mg/dl, respectively) were found to be significantly higher than normal control levels (P less than 0.005). The mean serum IgG, IgA and IgM concentration of the patients with Klebsiella infection (1102 +/- 340, 287 +/- 133 and 168 +/- 105 mg/dl, respectively), were also higher than normal levels but only IgM level differed significantly from the normal control levels (P less than 0.05). The difference in serum IgG and IgM between the patients with pulmonary tuberculosis and Klebsiella infection was statistically significant (P less than 0.05 and P less than 0.05, respectively). These findings reflect the polyclonal hypergammaglobulinemia found in chronic infections, on the one hand, and the rise of IgM of the primary immune response in acute infection, on the other.

Mahaim and James fibers as a basis for a unique variety of ventricular preexcitation.

This report concerns pathologic findings in a 54 year old woman with intermittent preexcitation who died of carcinoma of the breast. Electrocardiograms revealed predominantly normal sinus rhythm with a normal P-R interval and narrow QRS complex. Episodes of sinus rhythm, short P-R interval and QRS widening (with delta wave) were also recorded. During preexcitation QS complexes were noted in leads II, III, aVF, V1 and V4 to V6. Delta waves were negative in leads II, III, aVF and V1 isoelectric in leads V4 to V6 and positive only in leads I, aVL, V2 and V3. This case thus defies classification into any known variety of preexcitation. Complete serial sections, cut through the entire conduction system and both atrioventricular (A-V) rims, totaled 18,600 sections. These revealed no bundle of Kent. Instead, Mahaim fibers histologically identified as His bundle tissue gave off from the A-V bundle to both the right and the left sides of the septum associated with the normal fibers of James. This case reveals that (1) fibers of James can bypass the A-V node, (2) fibers of Mahaim can conduct, and (3) there are types of preexcitation in addition to types A and B.

The clinicopathologic features of cryoglobulinemic nephropathy.

Renal biopsy specimens from eight patients with cryoglobulinemic nephropathy were examined by light, electron, and immunofluorescence microscopy. The light microscopic features were not diagnostic. Characteristic ultrastructural findings were observed in all except one specimen and consisted of glomerular electron-dense deposits, which had a coarse, granular appearance at low-power magnifications and revealed tubular, annular and in a few cases, also fibrillar structures at high-power magnifications. Subendothelial deposits were a constant finding. The presence of intravascular thrombi (deposits), osmiophilic bodies, and crystals within the cytoplasm of the glomerular cells are also helpful for the diagnosis of this entity. Because of these specific findings, cryoglobulinemic nephropathy should be recognized as a clinicopathologic entity.

The effect of selective decontamination of the digestive tract on gastrointestinal enterococcal colonization in ITU patients.

OBJECTIVE: The effect of selective decontamination of the digestive tract (SDD) on Intensive Therapy Unit (ITU)-acquired enterococcal infection and colonization was studied. Changes in the predominant species isolated and resistance patterns to antimicrobial agents were also studied. DESIGN: Three groups were investigated: historical control (HC), contemporaneous control (CC) and patients receiving SDD (topical polymyxin, amphotericin B and tobramycin throughout ITU stay with intravenous ceftazidime for the first 3 days only). SETTING: Adult general ITU with 7 beds. PATIENTS: Patients with a nasogastric tube in situ and who were likely to remain in ITU for 48 h or longer were recruited. RESULTS: Enterococcal infections occurred in 3 of 84 HC patients and 2 of 91 CC patients. There were no unit-acquired enterococcal infections in the SDD group. There were 140 episodes of enterococcal colonization occurring in 112 patients, with significantly more in the SDD and CC groups (p < 0.05. There were no significant differences in antibiotic sensitivities between the three groups. Enterococcus faecalis was the most frequently isolated species. CONCLUSION: SDD does not predispose to enterococcal infection but does encourage colonization in patients receiving the regimen and other patients in ITU at the same. There is a complex interaction of factors which influence faecal flora and the likelihood of patients becoming colonized or infected with enterococci.

Single versus bilateral internal mammary artery grafts: 10-year outcome analysis.

BACKGROUND: The superior long-term patency of the internal mammary artery (IMA) confers important short-term and late survival advantages when grafted to the left anterior descending coronary artery. However, it remains uncertain whether patients derive additional survival benefit when both IMAs are used in coronary revascularization. METHODS: Between June 1983 and May 1986, 160 patients (mean age 60 years) received bilateral IMA grafts for coronary artery bypass procedures, and in 93% of patients, the right IMA was used to bypass the left coronary system. During a similar interval, a group of 161 patients matched for symptomatic status and extent of disease (mean age, 62 years) received a single left IMA and saphenous vein grafts. RESULTS: The two groups were similar with respect to gender, preoperative angina class, priority status, extent of coronary artery disease, left ventricular function, and number of distal anastomoses. Diabetes was more prevalent in the patient group receiving a single IMA graft (27% versus 17.5%; p = 0.05). Early outcome was similar in the two groups; operative mortality was 0.6% for the patient group receiving single IMA grafts and 0% for those with bilateral IMA grafts. The mean follow-up of 320 hospital survivors was 10 years. Univariate analysis revealed significantly fewer overall deaths in the patients receiving bilateral IMA grafts (n = 30; p = 0.05), and less late cardiac mortality (n = 12; p = 0.016). Ten-year actuarial survival for patients dismissed from the hospital was 76% for those receiving single IMA graft versus 85% for those receiving bilateral IMA grafts. Multivariate analysis revealed diabetes (risk ratio = 1.73), advancing age (risk ratio = 1.08), and lower ejection fraction (risk ratio = 1.01) to be the only significant predictors of late cardiac death. Use of a single IMA graft was not significant (p = 0.138) despite a risk ratio of 1.78. Use of only a single IMA graft correlated with an increased risk of angina recurrence (p < 0.001), late myocardial infarction (p = 0.019), and risk of any cardiac event (p < 0.001). CONCLUSIONS: Independent risk factors for late death were diabetes mellitus, older age, and reduced ejection fraction. Patients receiving bilateral IMA grafts had better long-term survival than those with a single IMA graft, but this was not independent of diabetes. Multivariate analysis, however, did confirm that compared with single arterial grafts, bilateral IMA grafting was an independent predictor of lower rates of angina recurrence, late myocardial infarction, and the composite end point of any cardiac event.

Parasystole and its variants.

Various mechanisms that cause deviations from the classical manifestations of a parasystolic rhythm are reviewed and illustrated by selected clinical electrocardiograms. They consist of: (1) Transient or continued fixed coupling of the ectopic beats, due to (a) synchronization of basic and parasystolic rhythms; (b) reversed coupling of the basic to the ectopic rhythm (unidirectional protection); (c) the operation of supernormal phase of excitability; and (d) intermittent parasystole, due to gap in the protection of the parasystolic center. (2) Irregularities in response to a regular parasystolic discharge may be caused by a second degree exit block, usually of Mobitz type II, rarely of type I. An electrophysiologic basis for the emergence and maintenance of parasystolic rhythms appears to be abnormal states of spontaneous diastolic (phase 4) depolarization in otherwise latent subsidiary cardiac pacemakers.

Corneal subepithelial monoclonal kappa IgG deposits in essential cryoglobulinaemia.

A 60-year-old man suffering from photophobia and visual disturbances was found to have bilateral superficial corneal grey-white gelatinous deposits. An abnormal cold-precipitable serum component was found and characterised as homogeneous IgG-kappa immunoglobulin. Corneal immunohistochemical examination revealed subepithelial IgG-kappa deposits, focally replacing Bowman's layer. The patient underwent superficial keratectomy in both eyes with satisfactory visual results.

Home nutrition survey in the UK: the patient's perspective.

A detailed survey questionnaire compiled by the executive committee of Patients on Intravenous and Nasogastric Nutrition Therapy (PINNT) was circulated in November 1991 to the postal addresses of all full (patient) members of PINNT in the UK. The objective of the survey was to identify current practices and problems of home nutrition support as seen from the patients perspective. 128 questionnaires were distributed. 87 (68%) analysable questionnaires were completed and returned. 77 were for parenteral nutrition (HPN) patients and 10 for patients on enteral nutrition (HEN). Areas of concern for patients include the practicalities of administration of lipid and additives, and problems associated with the appearance of air in infusion bags. Although most patients appeared happy with the home nutrition support services 18% commented on particular negative aspects. This survey highlights such areas which may not be identified during routine patient/clinician contact.

Effectiveness of low-dose melphalan treatment against a nonimmunogenic primary induced mouse plasmacytoma.

The fourth i.p. passage of the plasmacytoma "PR" induced by repeated i.p. injections was used for testing chemotherapy with melphalan. The development of "PR" ascitic tumours was slower and the survival time of inoculated mice was longer than that of MOPC-315 inoculated mice. Moreover, the myeloma protein secreted by the "PR" tumour cells, differed from MOPC-315 secreted myeloma protein in its electrophoretic mobility (fast gamma-2) and its characteristics as IgG immunoglobulin. Chemotherapy by a single injection of melphalan 7.5 mg/kg was effective in preventing the development of both MOPC-315 ascitic tumours and "PR" ascitic tumours. Mice cured from MOPC-315 tumours, however, developed antitumour response as shown by resistance to challenge with a high tumourigenic dose and by development of cytotoxic response in vitro against MOPC-315 tumour cells by spleen cells taken from the cured mice. On the other hand, mice cured from "PR" tumour by melphalan were highly susceptible to challenge and their spleen cells were not able to develop a cytotoxic response in vitro against target "PR" tumour cells.

Effects of gesture and target on 12- and 18-month-olds' joint visual attention to objects in front of or behind them.

Factors affecting joint visual attention in 12- and 18-month-olds were investigated. In Experiment 1 infants responded to 1 of 3 parental gestures: looking, looking and pointing, or looking, pointing, and verbalizing. Target objects were either identical to or distinctive from distractor objects. Targets were in front of or behind the infant to test G. E. Butterworth's (1991b) hypothesis that 12-month-olds do not follow gaze to objects behind them. Pointing elicited more episodes of joint visual attention than looking alone. Distinctive targets elicited more episodes of joint visual attention than identical targets. Although infants most reliably followed gestures to targets in front of them, even 12-month-olds followed gestures to targets behind them. In Experiment 2 parents were rotated so that the magnitude of their head turns to fixate front and back targets was equivalent. Infants looked more at front than at back targets, but there was also an effect of magnitude of head turn. Infants' relative neglect of back targets is partly due to the "size" of adult's gesture.

Effect of sternotomy direction on the incidence of inadvertent pleurotomy.

OBJECTIVE: Median sternotomy was performed by 2 different techniques in order to determine whether there was a difference in the incidence of inadvertent pleural entry. EXPERIMENTAL DESIGN: Patients were prospectively evaluated and reviewed at a mean follow-up interval of 8.2 months. PATIENTS AND METHODS: Ninety five consecutive patients underwent primary sternotomy at a single tertiary referral center. MEASURES: Planned outcome measures included, incidence of pleural entry, length of hospitalization, and chest tube site related postoperative morbidity. RESULTS: Group 1 (n=49) had sternotomy undertaken from the sternal notch proceeding downwards. Group 2 (n=46) underwent sternotomy performed from the xiphoid upwards. Mediastinal evaluation revealed a significant reduction in the incidence of pleural violation for group 1 (3) versus group 2 (11) (p=0.014). This difference was not found to be surgeon specific. CONCLUSIONS: Sternotomy undertaken from the sternal notch proceeding downwards is shown to be associated with a reduced incidence of inadvertent pleural entry. Potential advantages for this approach also include reduced respiratory morbidity, less chest tube site complications and a trend to reduced length of hospitalization.

Serum alpha fetal protein in a three year old child with hepatoma.

A 3 year old child with primary hepatocellular carcinoma and high AFP concentrations is described. Following hemihepatectomy, a sharp decrease and return to normal of serum AFP concentrations indicated the completeness of the surgical procedure. Repeat-normal serum AFP concentrations (less than 19 ng/ml), found during a three year follow-up, correlated well with the absence of clinical, laboratory and x-ray evidence of tumor recurrence. The differential diagnosis of abnormal AFP concentrations in childhood is discussed, and the importance of the AFP assay in the follow-up of post-hemihepatectomy patients for the assessment of the completeness of the surgical procedure, the prognosis, and the early detection of tumor recurrence is stressed.