Perspective: Quantum Hamiltonians for optical interactions.

The multipolar Hamiltonian of quantum electrodynamics is extensively employed in chemical and optical physics to treat rigorously the interaction of electromagnetic fields with matter. It is also widely used to evaluate intermolecular interactions. The multipolar version of the Hamiltonian is commonly obtained by carrying out a unitary transformation of the Coulomb gauge Hamiltonian that goes by the name of Power-Zienau-Woolley (PZW). Not only does the formulation provide excellent agreement with experiment, and versatility in its predictive ability, but also superior physical insight. Recently, the foundations and validity of the PZW Hamiltonian have been questioned, raising a concern over issues of gauge transformation and invariance, and whether observable quantities obtained from unitarily equivalent Hamiltonians are identical. Here, an in-depth analysis of theoretical foundations clarifies the issues and enables misconceptions to be identified. Claims of non-physicality are refuted: the PZW transformation and ensuing Hamiltonian are shown to rest on solid physical principles and secure theoretical ground.

Coding accuracy for Parkinson's disease hospital admissions: implications for healthcare planning in the UK.

OBJECTIVES: Hospital Episode Statistics data are used for healthcare planning and hospital reimbursements. Reliability of these data is dependent on the accuracy of individual hospitals reporting Secondary Uses Service (SUS) which includes hospitalisation. The number and coding accuracy for Parkinson's disease hospital admissions at a tertiary centre in Birmingham was assessed. STUDY DESIGN: Retrospective, routine-data-based study. METHODS: A retrospective electronic database search for all Parkinson's disease patients admitted to the tertiary hospital over a 4-year period (2009-2013) was performed on the SUS database using International Classification of Disease codes, and on the local inpatient electronic prescription database, Prescription and Information Communications System, using medication prescriptions. Capture-recapture methods were used to estimate the number of patients and admissions missed by both databases. RESULTS: From the two databases, between July 2009 and June 2013, 1068 patients with Parkinson's disease accounted for 1999 admissions. During these admissions, the Parkinson's disease was coded as a primary or secondary diagnosis. Ninety-one percent of these admissions were recorded on the SUS database. Capture-recapture methods estimated that the number of Parkinson's disease patients admitted during this period was 1127 patients (95% confidence interval: 1107-1146). A supplementary search of both SUS and Prescription and Information Communications System was undertaken using the hospital numbers of these 1068 patients. This identified another 479 admissions. SUS database under-estimated Parkinson's disease admissions by 27% during the study period. CONCLUSION: The accuracy of disease coding is critical for healthcare policy planning and must be improved. If the under-reporting of Parkinson's disease admissions on the SUS database is repeated nationally, expenditure on Parkinson's disease admissions in England is under-estimated by approximately £61 million per year.

Comment on "Gauge-invariant expectation values of the energy of a molecule in an electromagnetic field" [J. Chem. Phys. 144, 044109 (2016)].

The 'problem' identified in the paper [J. Chem.Phys. 144, 044109 (2016)] does not arise in a properly formulated non-relativistic Hamiltonian formalism for both classical and quantum electrodynamics.

Lessons learnt from the multi-centre LAparoscopic Versus Abdominal hysterectomy (LAVA) randomised controlled trial.

Background: The LAparoscopic Versus Abdominal hysterectomy (LAVA) randomised controlled trial comparing laparoscopic hysterectomy (LH) and abdominal hysterectomy (AH) closed prematurely on the grounds of futility. Here we identify the challenges faced and lessons learnt. Objectives: To explore the views and experiences of clinical/research staff in order to understand how these might act as barriers to trial participation and recruitment. Materials and Methods: Review of the trial progress and collation of the views and experiences of clinical/ research staff on all aspects of the trial. Data were collected from transcribed conversations, email, phone, or video conferencing interactions and analysed descriptively. Main outcome measures: Site set-up milestones, recruitment rates and reasons provided by clinical/research staff for site's declining to participate. Opinions, preferences and experiences of clinicians/researchers and challenges to participation and recruitment. Results: The mean time from initial site contact to opening was 253 days and 68 days to randomise their first participant. 265 patients were screened from 13 sites over 13 months, 154 were eligible, and 75 (59%) were randomised. Of the 53 not randomised, 23 (43%) women preferred LH whilst 6 (11%) preferred AH. The main reasons given for failure to recruit or activate set-up in the 21 sites open or in set-up, were lack of research/ clinical capacity imposed by the COVID-19 pandemic and lack of clinician equipoise. Conclusions: The main reasons for the LAVA trial failure were lack of equipoise amongst surgeons and the adverse impact of the COVID-19 pandemic on clinical/research services. What is new?: Surgeons' preference for laparoscopic hysterectomy is not shared by most patients. Many patients prefer an open hysterectomy to a laparoscopic one.

A rapid, topographical platelet activation assay.

Platelets are central in maintaining normal haemostasis and are responsible for the cessation of blood loss following vascular injury. Platelet adhesion, leading to thrombus formation, involves rapid and distinct morphological changes culminating in cell aggregation. Rapid and highly specific platelet diagnostic tests are currently being developed to enable monitoring of drug response in patients with cardiovascular diseases. For a diagnostic device to be effective it needs to be rapid and simple, requiring minimal user interaction and providing results with minimal delay. This study describes the development of a rapid, label free platform for assay platelet function and demonstrates its use to monitor the influence of anti-thrombotic drugs. A rapid, single-step cell purification surface immobilises platelets from whole blood onto a protein array at specific locations used to define the assay site. Morphological changes and cell aggregation properties of activated platelets are exploited and combined within a label free, rapid, dye displacement chamber to determine cell morphology. Stimulation-dependent changes in cell morphology are described using both high resolution AFM imaging and a dye displacement platform.

From particle to platelet: optimization of a stable, high brightness fluorescent nanoparticle based cell detection platform.

Nanoparticles are increasingly used as diagnostic tools due to the ease with which their surface chemistry, optical and physical properties can be controlled. Molecules, drugs, enzymes and fluorophores can be protected within the particle core or conjugated externally conferring nanoparticle biocompatibility, target specificity or environmental sensitivity. This study details the development and characterisation of stable, bright, dye-doped silica nanoparticles which are surface functionalised with PAMAM dendrimers to enable efficient conjugation to platelet activation-specific antibodies. We present the physical and optical properties and demonstrate colloidal stability. We also provide the first evidence of how NPs can be employed to specifically label human platelets immobilised on a lab-on-a-chip platform. Using a single step protocol, we demonstrate highly specific platelet labelling with the distribution of antibody-conjugated NPs matching that expected for the platelet GPIIb/IIIa receptor. The work highlights the potential of functionalized fluorescent NPs as diagnostic tools for cardiovascular disease. FROM THE CLINICAL EDITOR: This study details the development and characterization of PAMAM dendrimer functionalized, stable, and bright dye-doped silica nanoparticles that enable efficient conjugation to platelet activation-specific antibodies. These fluorescent NPs may specifically label human platelets that can be used as diagnostic tools for cardiovascular disease.

On the quantum theory of molecules.

Transition state theory was introduced in 1930s to account for chemical reactions. Central to this theory is the idea of a potential energy surface (PES). It was assumed that such a surface could be constructed using eigensolutions of the Schrödinger equation for the molecular (Coulomb) Hamiltonian but at that time such calculations were not possible. Nowadays quantum mechanical ab initio electronic structure calculations are routine and from their results PESs can be constructed which are believed to approximate those assumed derivable from the eigensolutions. It is argued here that this belief is unfounded. It is suggested that the potential energy surface construction is more appropriately regarded as a legitimate and effective modification of quantum mechanics for chemical purposes.

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson's disease: a study protocol for a randomised controlled trial.

BACKGROUND: Parkinson's disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals' needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. METHODS/DESIGN: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. PRIMARY OUTCOME: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson's Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. DISCUSSION: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016.

The vasovagal tonus index as a prognostic indicator in dogs with dilated cardiomyopathy.

OBJECTIVES: To investigate the prognostic and diagnostic value of heart rate variability (HRV) using the vasovagal tonus index (VVTI) in dogs suffering from idiopathic dilated cardiomyopathy (DCM). METHODS: Electrocardiographic (ECG) recordings of 369 patients presented to a referral centre between 1993 and 2006 were reviewed. RESULTS: VVTI values were calculated from 132 dogs. Lower VVTI values were found in patients in International Small Animal Cardiac Health Council (ISACHC) heart failure (HF) class 2 and 3 compared with class 1. VVTI was found to be positively correlated with survival time (ST) in class 2 and 3 patients. When a cut-off value of 7.59 for VVTI was used, the test could differentiate patients in ISACHC HF class 1 versus 2 and 3 with a sensitivity of 89 per cent and a specificity of 62.5 per cent. The ST for patients with VVTI values less than 7.59 was significantly lower. CLINICAL SIGNIFICANCE: The VVTI is a useful index, obtained from a standard ECG recording that estimates HRV in dogs and does not require any specific equipment for its calculation. It can be useful as a diagnostic tool to assess the severity of HF and is a useful prognostic tool in dogs with DCM.

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study.

BACKGROUND: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. OBJECTIVES: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

Atrial myocarditis as a cause of sinus arrest in a dog.

A 10-year-old male cairn terrier cross was presented with a history of myxomatous mitral valve disease diagnosed six months previously and with a four-week history of intermittent collapse. On 24 hour electrocardiograph (Holter) analysis, periods of no discernable electrical cardiac activity, which coincided with three collapsing episodes, were identified. Unfortunately, on re-presentation for removal of the Holter monitor, the dog collapsed and died. A post-mortem examination was conducted, and histology of the right and left atrium showed evidence of myocarditis. This is the first reported case, to our knowledge, of collapse because of electrical asystole in a dog with atrial myocarditis.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. ANIMALS: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. METHODS: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. RESULTS: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

Respi-Care. An innovative home care program for the patient with chronic obstructive pulmonary disease.

The purpose of the present study was to evaluate the effectiveness of a hospital-based home care program for a group of patients with severe COPD. Respi-Care was a multidisciplinary home care program administered by Norwalk Hospital in cooperation with the public health nursing departments of the city of Norwalk and the town of Wilton, Conn. The overall goal of Respi-Care was to provide more comprehensive home care services to patients previously requiring frequent hospitalizations by combining the advantages of hospital resources and community agencies through a unique cooperative effort. Preprogram and on-program data were collected on the following variables for the 48 months of Respi-Care operation: hospitalizations; hospital days; emergency room visits; home care services; and the costs of these services. Costs of operating the Respi-Care program were included in on-program data. Seventeen subjects completed 320.5 months on Respi-Care. Each subject was matched to an equal length of time prior to entering the program, for a total of 641 months analyzed. There were 88 preprogram hospitalizations for the group; hospitalizations while participating in Respi-Care dropped to 53 (p = 0.022; paired t statistics). On-program hospital days showed a significant decrease, from 1,181 preprogram days to 667 on-program days (p = 0.024). Emergency room visits decreased from 105 before the program to 64 during the program (p = 0.017). Costs of care also decreased. Costs for hospitalizations, emergency room visits, and home care fell from $908,031 to $802,999, resulting in a $105,032 savings or $328 per patient per month.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional status and survival following pulmonary rehabilitation.

BACKGROUND: Functional exercise capacity has been shown to be a strong predictor of survival following pulmonary rehabilitation. This study evaluated whether questionnaire-rated functional status is also predictive of survival. PATIENTS AND METHODS: Following pulmonary rehabilitation, patients with advanced chronic lung disease were evaluated for survival, 6-min walk distance, and questionnaire-rated functional status. The latter was measured using the pulmonary functional status scale, which has subscores of functional activities, psychological status, and dyspnea. Information on survival was available on 149 patients. RESULTS: The mean age was 69 years, and 45% of patients were male. Eighty-nine percent had a diagnosis of COPD, and their FEV(1) was 37+/-18% of predicted. Ninety-one (61%) were married. The 3-year survival for the group was 85%. Age, gender, body mass index, and primary diagnosis were not related to survival. Variables strongly associated with increased survival following pulmonary rehabilitation included a higher postrehabilitation Functional Activities score, a longer postrehabilitation 6-min walk distance, and being married (vs widowed, single, or divorced). Disease severity variables associated with survival included an initial referral to outpatient pulmonary rehabilitation, no supplemental oxygen requirement, and a higher percent-predicted FEV(1). CONCLUSION: Indicators of functional status are strong predictors of survival in patients with advanced lung disease.

Benefits and risks of episiotomy: a review of the English-language literature since 1980. Part I.

The professional literature on the benefits and risks of episiotomy was last reviewed critically in 1983, encompassing material published through 1980. This paper reviews the evidence accumulated since then. (Part II follows in this issue.) It is concluded that episiotomies prevent anterior perineal lacerations (which carry minimal morbidity), but fail to accomplish any of the other maternal or fetal benefits traditionally ascribed, including prevention of perineal damage and its sequelae, prevention of pelvic floor relaxation and its sequelae, and protection of the newborn from either intracranial hemorrhage or intrapartum asphyxia. In the process of affording this one small advantage, the incision substantially increases maternal blood loss, the average depth of posterior perineal injury, the risk of anal sphincter damage and its attendant long-term morbidity (at least for midline episiotomy), the risk of improper perineal wound healing, and the amount of pain in the first several postpartum days.

Benefits and risks of episiotomy: a review of the English-language literature since 1980. Part II.

Mediolateral and, to a lesser degree, midline episiotomies substantially increase the amount of blood loss at delivery; in fact, simple avoidance of episiotomy may be the most powerful means the delivery attendant has to prevent excessive intrapartum hemorrhage. The long-term morbidity of the anal sphincter damage induced by episiotomy, particularly midline, has generally been underestimated in both its frequency and severity. Other potential fetal and maternal complications of episiotomies, although rare, are numerous and serious. The overall degree of risk that accompanies this procedure could only be justified by a clear and overriding benefit, which, as discussed under "Benefits" earlier in this review, does not appear to exist.

Evaluating integrated urban water systems alternatives for Brisbane, Australia.

The Brazil Development Study investigates the feasibility of alternative approaches to providing sustainable water services to a 226 ha mixed residential and industrial greenfield development within the city of Brisbane, Australia. The alternatives include techniques such a the use of rainwater tanks, water use efficiency, a local wastewater treatment plant for recycling of reclaimed water and composting toilets amongst others. This paper evaluates a series of urban development scenarios against the objectives of the study. The insights gained into the drivers for cost and environmental impact for this particular site are discussed as well as a number of issues of concern and challenges to Council and the community.

Sexual dysfunction and COPD: problems and management.

Engaging in sexual activity is a common difficulty for persons with chronic obstructive pulmonary disease (COPD). Misconceptions, ignorance, medications and poor physical or mental health, all factors common to this population, contribute to sexual dysfunction. The nurse practitioner can help patients with COPD deal with the problems of sexual function by assessing possible contributing factors, teaching ways to minimize these factors and to increase exercise tolerance, and encouraging other expressions of love, affection and intimacy.

Intracellular pH-sensing using core/shell silica nanoparticles.

An in-depth understanding of biochemical processes occurring within biological systems is key for early diagnosis of disease and identification of appropriate treatments. Nanobiophotonics offers huge potential benefits for intracellular diagnostics and therapeutics. Intracellular sensing using fluorescent nanoparticles is a potentially useful tool for real-time, in vivo monitoring of important cellular analytes. This work is focused on synthesis of optical chemical nanosensors for the quantitative analysis of pH inside living cells. The structure of the nanosensor comprises a biofriendly silica matrix with co-encapsulated Texas Red, acting as a reference dye, and pH-sensitive fluorescein isothiocyanate enabling ratiometric quantitative environmental detection. In order to obtain silica-based nanoparticles -70 nm in size, a modified sol-gel-based Stöber method was employed. The potential of these nanosensors for intracellular pH monitoring is demonstrated inside a live human embryonic kidney cell line whereby a significant change in fluorescence is observed when the cell pH is switched from acidic to basic. High loading efficiencies of nanoparticles into the cells is seen, with little effect on cell morphology even following extended nanoparticle exposure (up to 72 h). Nanoparticle incubation time and the fast response of the nanosensor (-2 s) make it a very powerful tool in monitoring the processes occurring within the cytosol.