The ultrastructural changes observed during sporocyst formation and the structure of the sporocyst wall was examined in oocysts which had been allowed to sporulate for between 12 and 48 hours at 27 degrees C. As the spherical sporoblast developed into the sporocyst the cytoplasmic mass became ellipsoidal in shape although no change was noted in the organelle compliment, which cosisted of two nuclei plus a number of polysaccharide granules, lipid globules, mitochondria, Golgi bodies, and some rough endoplasmic reticulum. The sporocyst wall consisted of a thin outer layer (15-20 nm) which was formed from two limiting membranes of the sporoblast and an inner layer (40-50 nm) which was comprised of four curved plates. This inner layer was formed under the outer layer and, although no specific cytoplasmic organelle disappeared with its formation, some unit membranes were observed close to the plasmalemma during its formation. Each curved plate has a marginal swelling and an interposing strip of material is present between the margins of adjacent plates. The plates are joined to the interposing strip by a thin band of osmiophilic material. In oblique and tangential sections through the plates two types of cross banding were observed which differed in periodicity.

Nuclear phospholipase C-gamma 1 can be phosphorylated by nuclear membrane located epidermal growth factor receptor sequel to epidermal growth factor-mediated signaling to the nucleus. The function of mouse liver phospholipase C-gamma 1 is attributed to a 120 kDa protein fragment which has been found to be a proteolytic product of the 150 kDa native nuclear enzyme. The tyrosine-phosphorylated 120 kDa protein band interacts with activated EGFR, binds phosphatidyl-3-OH kinase enhancer, and activates nuclear phosphatidylinositol-3-OH-kinase, and is capable of generating diacylglycerol in response to the epidermal growth factor signal to the nucleus in vivo. Thus a mechanism for nuclear production of inositol-1,4,5-trisphophate is unraveled. Nuclear generated inositol-1,4,5-trisphophate interacts with the inner membrane located inositol-1,4,5-trisphophate receptor and sequesters calcium into the nucleoplasm. Nuclear inositol-1,4,5-trisphophate receptor is phosphorylated by native nuclear protein kinase C which enhances the receptor-ligand interaction. Nuclear calcium-ATPase and inositol-1,3,4,5-tetrakisphophate receptor are located on the outer nuclear membrane, thus facilitating calcium transport into the nuclear envelope lumen either by ATP or inositol-1,3,4,5-tetrakisphophate depending upon the external free calcium concentrations. Nuclear calcium ATPase is phosphorylated by cyclic AMP-dependent protein kinase with enhanced calcium pumping activity. A holistic picture emerges here where tyrosine phosphorylation compliments serine phosphorylation of key moieties regulating nuclear calcium signaling. Evidence are forwarded in favor of proteolysis having a profound implications in nuclear calcium homeostasis in particular and signal transduction in general.

Neurological involvement is relatively common in the majority of systemic autoimmune diseases and may lead to severe morbidity and mortality, if not promptly treated. Treatment options vary greatly, depending on the underlying systemic pathophysiology and the associated neurological symptoms. Selecting the appropriate therapeutic scheme is further complicated by the lack of definite therapeutic guidelines, the necessity to differentiate primary neurological syndromes from those related to the underlying systemic disease, and to sort out adverse neurological manifestations caused by immunosuppressants or the biological agents used to treat the primary disease. Immunotherapy is a sine qua non for treating most, if not all, neurological conditions presenting in the context of systemic autoimmunity. Specific agents include classical immune modulators such as corticosteroids, cyclophosphamide, intravenous immunoglobulin, and plasma exchange, as well as numerous biological therapies, for example anti-tumor necrosis factor agents and monoclonal antibodies that target various immune pathways such as B cells, cytokines, and co-stimulatory molecules. However, experience regarding the use of these agents in neurological complications of systemic diseases is mainly empirical or based on small uncontrolled studies and case series. The aim of this review is to present the state-of-the-art therapies applied in various neurological manifestations encountered in the context of systemic autoimmune diseases; evaluate all treatment options on the basis of existing guidelines; and compliment these data with our personal experience derived from a large number of patients.

The long-term survival of lung cancer patients treated with conventional therapies (surgery, radiation therapy and chemotherapy) remains poor and has changed little in decades. The need for novel approaches remains high and gene therapy holds promise in this area. A number of genes have been shown in vitro, in animal studies and most recently, in human clinical trials, to have antitumor actions. However, a number of problems still exist and success in human patients to date has been marginal. Among the numerous considerations are the efficiency of delivery of the gene to the tumor or, if an indirect effect is the aim, possibly nontumor tissues, the efficiency and persistence of expression of the therapeutic gene, the specificity of the gene action against the tumor, potential toxic or pathogenic consequences of either the genes or the delivery vectors used, convenience of the therapy and how likely the therapy will compliment or complicate other conventional anticancer therapies. After the cloning of the cystic fibrosis gene, there was great interest in the noninvasive delivery of genes directly to the pulmonary surfaces by aerosol. Clearly, this approach could have application to some pulmonary cancers as well and most early efforts focused mainly on the use of nonviral vectors, primarily cationic lipids. Unfortunately, nebulization shear forces and inefficient pulmonary uptake and expression of plasmid DNA-cationic lipid formulations have generally resulted in a lack of therapeutic effect, so much of this work has diminished in recent years. Polyethyleneimine (PEI)-based formulations have proven stable during nebulization and result in nearly 100% efficient transfection throughout the airways and lung parenchyma. Therapeutic responses have been obtained in several animal lung tumor models when PEI-based formulations of p53 and other antitumor genes were delivered by aerosol. In addition, this mode of delivery seems to be associated with low toxicity and results in little or none of the immunostimulatory response typically associated with the delivery of bacterially produced plasmid DNA containing unmethylated CpG motifs, which has presented a challenge to repeated gene therapy via other modes of delivery. Other potential applications of PEI aerosol gene delivery include the treatment of asthma, lung alveolitis and fibrosis and a variety of monogeneic diseases such as cystic fibrosis and alpha-1-antitrypsin deficiency. In addition, a wide range of conditions treatable via genetic immunization could benefit from this approach to gene delivery as well.

Centrally injected neuropeptide Y (NPY) is a potent stimulant of ingestive behavior capable of augmenting both food and fluid intake in fully satiated animals. To gain further insight into NPY's mechanism of action, we recorded patterns of licking behavior in rats drinking sweetened condensed milk solutions immediately after lateral ventricular injection of NPY (10 micrograms) or vehicle. In a separate study, we examined licking patterns after 23 h food deprivation (FD) that produced approximately the same total intake as NPY. Consistent with previous reports, we found NPY stimulated intake by increasing total ingestion time and total volume consumed during a 1-h test. Although NPY increased the number of bouts of licking and shortened pauses between bouts, it also decreased mean bout size, bout duration and within-bout lick rate (local rate). It had no significant effect on start latency or lick efficiency (licks/ml). Further analyses revealed that NPY attenuated satiety (reduced slope of lick-rate functions with session time) but had no significant effect on the beginning lick rate, a measure related to orosensory excitation. In contrast to NPY, FD increased both the beginning lick rate and individual bout size without changing either the mean number of bouts or the pause between bouts. In general, NPY stimulated an intermittent pattern of licking and delayed satiation whereas FD increased the initial rate of licking and the size of individual bouts without changing the basic licking pattern. The increase in initial lick rate suggests that FD, unlike NPY, enhances orosensory stimulation. These data compliment previous results showing that NPY increases the motivation to eat.(ABSTRACT TRUNCATED AT 250 WORDS)

The current delineation of the molecular basis of cancer provides a strong rationale to consider gene therapy approaches for cancer as a complement to other cancer therapies. Phase III trials focused on adenoviral vector-mediated delivery of wild-type p53 to compliment p53 mutations were recently initiated for head and neck cancer and ovarian cancer. Clinical testing of the tumor inhibitory gene E1A, delivered by synthetic vectors is ongoing. Positive clinical data from these clinical studies will establish the use of gene therapy as a component of the multimodal treatment for certain cancers.

MomConnect is an mHealth initiative giving pregnant women information via SMS. We report on an analysis of the compliments and especially complaints component of the feedback. We scrutinised the electronic databases containing information on the first seventeen months of operation of MomConnect. During this time, 583,929 pregnant women were registered on MomConnect, representing approximately 46 per cent of pregnant women booking their pregnancy in the public sector in South Africa. These women gave feedback on services received: 4173 compliments and 690 complaints. Nearly three quarters (74 per cent) of all complaints were resolved. The complaints were classified into those related to health services (29 per cent), staff (22 per cent), health systems (42 per cent) and other (6 per cent). These complaints were fed back to managers in the health facilities. This has resulted in improvements in the quality of services, e.g. decreased drug stock-outs and change of behaviour of some health workers.

OBJECTIVE

The retinoblastoma protein (pRB) is a key regulator of the G1 cell cycle checkpoint and has been implicated as having a role in G1 arrest and apoptosis induced by radiation damage. In this report we examine the association between pRB expression and radiation response in patients treated between 1960 and 1983 with preoperative radiotherapy (50 Gy in 25 fractions) followed 4-6 weeks later by radical cystectomy. The correlation of pRB to patient outcome and how this relationship is complimentary to that seen with p53 staining status is also described.

METHODS

Immunohistochemical staining of pRB and p53 in paraffin-embedded tumor sections using WL-1 anti-RB and DO1 anti-p53 antibodies was considered adequate in 98 and 97 pretreatment tumor samples, respectively. There were 46 patients with clinical Stage T2, 28 with Stage T3a, and 24 with Stage T3b disease. The median age was 62 years and follow-up for those living was 85 months.

RESULTS

Staining for pRB was negative in 30% of the cases. Correlations were observed between pRB negativity and high pretreatment apoptosis level (p = 0.06), locally advanced clinical stage (p = 0.01), increased clinical-to-pathologic downstaging (p = 0.014), and more pathologic complete responses (Path-CRs; p = 0.019). Several other factors were tested and were not associated with pRB status, including p53 expression. RB status was the only pretreatment prognostic factor in the univariate analyses that correlated with downstaging and was independently associated with Path-CR using multivariate logistic regression. Despite these significant relationships, no correlations with patient outcome were observed when the entire cohort was analyzed. Restriction of the analyses to Stage T3b patients, however, revealed that pRB negativity predicted for enhanced distant metastasis freedom (p = 0.006, log rank) and overall survival (p = 0.02). The overexpression of p53 also correlated with distant metastasis freedom and overall survival in Stage T3b patients. Patient outcome was best when RB negative and p53 negative staining were seen.

CONCLUSIONS

Our results indicate that loss of RB function as measured by immunohistochemical staining is the strongest correlate of radiation response thus far recognized. Loss of RB expression also predicted for poor outcome in Stage T3b patients, which appeared to compliment the finding of normal p53 expression. While normal RB protein expression is usually associated with better patient outcome, other series have not examined patients treated with radiotherapy. The absence of pRB may be a useful marker for selecting patients for bladder preservation with radiotherapy, particularly when wild-type p53 is present.

Expanding the repertoire of reactions available to enzymes is an enduring challenge in biocatalysis. Owing to the synthetic versatility of transition metals, metalloenzymes have been favored targets for achieving new catalytic functions. Although less well explored, enzymes lacking metal centers can also be effective catalysts for non-natural reactions, providing access to reaction modalities that compliment those available to metals. By understanding how these activation modes can reveal new functions, strategies can be developed to access novel biocatalytic reactions. This review will cover discoveries in the last two years which access catalytic reactions that go beyond the native repertoire of metal-free biocatalysts.

The use of cadavers to teach anatomy is well established, but limitations with this approach have led to the introduction of alternative teaching methods. One such method is the use of three-dimensional virtual reality computer models. An interactive, three-dimensional computer model of human forearm anterior compartment musculoskeletal anatomy was produced using the open source 3D imaging program "Blender." The aim was to evaluate the use of 3D virtual reality when compared with traditional anatomy teaching methods. Three groups were identified from the University of Manchester second year Human Anatomy Research Skills Module class: a "control" group (no prior knowledge of forearm anatomy), a "traditional methods" group (taught using dissection and textbooks), and a "model" group (taught solely using e-resource). The groups were assessed on anatomy of the forearm by a ten question practical examination. ANOVA analysis showed the model group mean test score to be significantly higher than the control group (mean 7.25 vs. 1.46, P < 0.001) and not significantly different to the traditional methods group (mean 6.87, P>> 0.5). Feedback from all users of the e-resource was positive. Virtual reality anatomy learning can be used to compliment traditional teaching methods effectively.

Introduction Historically, the quality and performance of prehospital emergency care (PEC) has been assessed largely based on surrogate, non-clinical endpoints such as response time intervals or other crude measures of care (eg, stakeholder satisfaction). However, advances in Emergency Medical Services (EMS) systems and services world-wide have seen their scope and reach continue to expand. This has dictated that novel measures of performance be implemented to compliment this growth. Significant progress has been made in this area, largely in the form of the development of evidence-informed quality indicators (QIs) of PEC. Problem Quality indicators represent an increasingly popular component of health care quality and performance measurement. However, little is known about the development of QIs in the PEC environment. The purpose of this study was to assess the development and characteristics of PEC-specific QIs in the literature.

METHODS

A scoping review was conducted through a search of PubMed (National Center for Biotechnology Information, National Institutes of Health; Bethesda, Maryland USA); EMBase (Elsevier; Amsterdam, Netherlands); CINAHL (EBSCO Information Services; Ipswich, Massachusetts USA); Web of Science (Thomson Reuters; New York, New York USA); and the Cochrane Library (The Cochrane Collaboration; Oxford, United Kingdom). To increase the sensitivity of the literature, a search of the grey literature and review of select websites was additionally conducted. Articles were selected that proposed at least one PEC QI and whose aim was to discuss, analyze, or promote quality measurement in the PEC environment.

RESULTS

The majority of research (n=25 articles) was published within the last decade (68.0%) and largely originated within the USA (68.0%). Delphi and observational methodologies were the most commonly employed for QI development (28.0%). A total of 331 QIs were identified via the article review, with an additional 15 QIs identified via the website review. Of all, 42.8% were categorized as primarily Clinical, with Out-of-Hospital Cardiac Arrest contributing the highest number within this domain (30.4%). Of the QIs categorized as Non-Clinical (57.2%), Time-Based Intervals contributed the greatest number (28.8%). Population on Whom the Data Collection was Constructed made up the most commonly reported QI component (79.8%), followed by a Descriptive Statement (63.6%). Least reported were Timing of Data Collection (12.1%) and Timing of Reporting (12.1%). Pilot testing of the QIs was reported on 34.7% of QIs identified in the review.

CONCLUSIONS

Overall, there is considerable interest in the understanding and development of PEC quality measurement. However, closer attention to the details and reporting of QIs is required for research of this type to be more easily extrapolated and generalized. Howard I , Cameron P , Wallis L , Castren M , Lindstrom V . Quality indicators for evaluating prehospital emergency care: a scoping review. Prehosp Disaster Med. 2018;33(1):43-52.

This paper incorporates the findings from a multidisciplinary meeting on diabetic nephropathy and its renal and cardiovascular complications into a review article. The epidemic of obesity and the growing elderly population in the United States are primary drivers of a secondary epidemic of incipient type 2 diabetes mellitus and diabetic nephropathy. Current therapies aim to treat blood pressure, particularly with agents that block the renin-angiotensin system, to a target of 130/80 mm Hg. However, even lower blood pressure targets may be optimal. Control of hyperglycemia and dyslipidemia, smoking cessation, exercise, and weight loss all compliment blood pressure control and are achieved most effectively when the patient, provider, and health system are aligned with these goals. Once end-stage renal disease (ESRD) is reached, patients enter the highest cardiovascular risk-state appreciated in human medicine. Because of uniform access to care in the United States, advanced data systems, and circulatory system (intravascular) access in most patients, the ESRD population should be the future sampling frame for newer treatments tested in both prospective cohort and randomized trials. Cardiorenal risk, or the degree of excess cardiovascular risk incurred by patients with chronic kidney disease and ESRD, is a state offering considerable research opportunities for novel cardiovascular risk factors. Future studies should fully consider the possibility that improved outcomes would be achieved at a greater cost; thus, cost-effectiveness studies are essential for understanding the economic aspects of implementation. The goal of an ideal clinical trial would be ESRD prevention; however, pragmatic objectives such as a greater understanding of therapeutic toxicities should also be explored in this population.

Antimicrobial resistance is a global public health crisis and a national security threat to the United States, as stated in an executive order signed by the president in September 2014. This crisis is a result of indiscriminant antimicrobial use, which promotes selection for resistant organisms, increases the risk of adverse drug events, and renders patients vulnerable to drug-resistant infections. Antimicrobial stewardship is a key measure to combat antimicrobial resistance and specifically seeks to do this by improving antimicrobial use. Antimicrobial stewardship compliments infection control practices and it is important to note that these 2 disciplines are distinct and cannot be discussed interchangeably. Antimicrobial stewardship promotes the appropriate diagnosis, drug, dose, and duration of treatment. The appropriate diagnosis falls into the hands of the prescriber and clinical staff. Optimal antimicrobial drug selection, dosing strategy, and duration of treatment, however, often require expertise in antimicrobial therapy, such as an infectious disease-trained physician or pharmacist. Therefore, successful antimicrobial stewardship programs must be comprehensive and interdisciplinary. Most antimicrobial stewardship programs focus on hospitals; yet, in long-term care, up to 75% of antimicrobial use is inappropriate or unnecessary. Thus, one of the most pressing areas in need for antimicrobial stewardship is in long-term care facilities. Unfortunately, there is little evidence that describes effective antimicrobial stewardship interventions in this setting. This review discusses the need for and barriers to antimicrobial stewardship in long-term care facilities. Additionally, this review describes prior interventions that have been implemented and tested to improve antimicrobial use in long-term care facilities.

In human SH-SY5Y neuroblastoma (NB) cells, nascent immature N-glycosylated 110kDa TrkA moves rapidly from the endoplasmic reticulum (ER) to the Golgi Network (GN), where it matures into the 140kDa receptor prior to being transported to the cell surface, creating GN and cell surface pools of inactive receptor maintained below the spontaneous activation threshold by a full compliment of inhibitory domains and endogenous PTPases. In contrast, the oncogenic alternative TrkAIII splice variant is not expressed at the cell surface but re-localises to intracellular membranes, within which it exhibits spontaneous ERGIC/COPI-associated activation and oncogenic Akt signalling. In this study, we characterise the mechanism responsible for TrkAIII re-localisation. Spontaneous TrkAIII activation, facilitated by D4 IG-like domain and N-glycosylation site omission, increases spontaneous activation potential by altering intracellular trafficking, inhibiting cell surface expression and eliminating an important inhibitory domain. TrkAIII, spontaneously activated within the permissive ERGIC/COPI compartment, rather than moving in an anterograde direction to the GN exhibits retrograde transport back to the ER, where it is inactivated. This sets-up self-perpetuating TrkAIII re-cycling between the ERGIC and ER, that ensures continual accumulation above the spontaneous activation threshold of the ERGIC/COPI compartment. This is reversed by TrkA tyrosine kinase inhibitors, which promote anterograde transport of inactivated TrkAIII to the GN, resulting in GN-associated TrkAIII maturation to a 120kDa species that is degraded at the proteasome.

During social interactions, listeners weigh the importance of linguistic and extra-linguistic speech cues (prosody) to infer the true intentions of the speaker in reference to what is actually said. In this study, we investigated what brain processes allow listeners to detect when a spoken compliment is meant to be sincere (true compliment) or not ("white lie"). Electroencephalograms of 29 participants were recorded while they listened to Question-Response pairs, where the response was expressed in either a sincere or insincere tone (e.g., "So, what did you think of my presentation?"/"I found it really interesting."). Participants judged whether the response was sincere or not. Behavioral results showed that prosody could be effectively used to discern the intended sincerity of compliments. Analysis of temporal and spatial characteristics of event-related potentials (P200, N400, P600) uncovered significant effects of prosody on P600 amplitudes, which were greater in response to sincere versus insincere compliments. Using low resolution brain electromagnetic tomography (LORETA), we determined that the anatomical sources of this activity were likely located in the (left) insula, consistent with previous reports of insular activity in the perception of lies and concealments. These data extend knowledge of the neurocognitive mechanisms that permit context-appropriate inferences about speaker feelings and intentions during interpersonal communication.

Whilst the phenomenon of an electrical resting membrane potential (RMP) is a central tenet of biology, it is nearly always discussed as a phenomenon that facilitates the propagation of action potentials in excitable tissue, muscle, and nerve. However, as ion channel research shifts beyond these tissues, it became clear that the RMP is a feature of virtually all cells studied. The RMP is maintained by the cell's compliment of ion channels. Transcriptome sequencing is increasingly revealing that equally rich compliments of ion channels exist in both excitable and non-excitable tissue. In this review, we discuss a range of critical roles that the RMP has in a variety of cell types beyond the action potential. Whereas most biologists would perceive that the RMP is primarily about excitability, the data show that in fact excitability is only a small part of it. Emerging evidence show that a dynamic membrane potential is critical for many other processes including cell cycle, cell-volume control, proliferation, muscle contraction (even in the absence of an action potential), and wound healing. Modulation of the RMP is therefore a potential target for many new drugs targeting a range of diseases and biological functions from cancer through to wound healing and is likely to be key to the development of successful stem cell therapies.

Glucocorticoids are steroid hormones which, among other functions, exert an antiinflammatory effect. Endogenous glucocorticoids are normally secreted by the adrenal gland in discrete bursts. It is becoming increasingly evident that this pulsatile secretion pattern, leading to ultradian rhythms of plasma glucocorticoid levels, may have important downstream regulatory effects on glucocorticoid-responsive genes. Mathematical modeling of this system can compliment recent experimental data and quantitatively evaluate hypothesized mechanistic underpinnings of differential pulsatile signal transduction. In this paper, we describe an integrated model of pulsatile secretion of glucocorticoids by the hypothalamic-pituitary-adrenal (HPA) axis and the pharmacodynamic effect of glucocorticoids. This model is used to investigate the difference in transcriptional responses to pulsatile and constant glucocorticoid exposure. Nonlinearity in ligand-receptor kinetics leads to the differential expression of glucocorticoid-responsive genes in response to different patterns of glucocorticoid secretion, even when the total amount of glucocorticoid exposure is held constant. Understanding the implications of ultradian rhythms in glucocorticoids is important in studying the dysregulation of HPA axis function leading to altered glucocorticoid secretion patterns in disease.

The construction of high capacity data sharing networks to support increasing government and commercial data exchange has highlighted a key roadblock: the content of existing Internet-connected information remains siloed due to a multiplicity of local languages and data dictionaries. This lack of a digital lingua franca is obvious in the domain of human food as materials travel from their wild or farm origin, through processing and distribution chains, to consumers. Well defined, hierarchical vocabulary, connected with logical relationships-in other words, an ontology-is urgently needed to help tackle data harmonization problems that span the domains of food security, safety, quality, production, distribution, and consumer health and convenience. FoodOn (http://foodon.org) is a consortium-driven project to build a comprehensive and easily accessible global farm-to-fork ontology about food, that accurately and consistently describes foods commonly known in cultures from around the world. FoodOn addresses food product terminology gaps and supports food traceability. Focusing on human and domesticated animal food description, FoodOn contains animal and plant food sources, food categories and products, and other facets like preservation processes, contact surfaces, and packaging. Much of FoodOn's vocabulary comes from transforming LanguaL, a mature and popular food indexing thesaurus, into a World Wide Web Consortium (W3C) OWL Web Ontology Language-formatted vocabulary that provides system interoperability, quality control, and software-driven intelligence. FoodOn compliments other technologies facilitating food traceability, which is becoming critical in this age of increasing globalization of food networks.

Transanal endoscopic microsurgery (TEMS) is a well established method of accurate resection of specimens from the rectum under binocular vision. This review examines its role in the treatment of benign conditions of the rectum and the evidence to support its use and compliment existing endoscopic treatments. The evolution of TEMS in early rectal cancer and the concepts and outcomes of how it has been utilised to treat patients so far are presented. The bespoke nature of early rectal cancer treatment is changing the standard algorithms of rectal cancer care. The future of TEMS in the organ preserving treatment of early rectal cancer is discussed and how as clinicians we are able to select the correct patients for neoadjuvant or radical treatments accurately. The role of radiotherapy and outcomes from combination treatment using TEMS are presented with suggestions for areas of future research.

The isolation and identification of a chlamydial agent from an equine fetus is reported. The fetus was aborted by a mare with respiratory disease and fever in the 9th month of pregnancy. The serum of the mare was investigated by the compliment fixation test. Specific antibodies were detected for chlamydial antigen in a titer of>> 1:40 and for equine herpes virus 1 antigen in a titer of 1:32. Pathological lesions were not found in the organs of the fetus. Chlamydiae were detected in the placenta by ELISA and subsequently isolated by cell culture. Using PCR technique the agent was identified as Chlamydophila psittaci.

All genes critical for plasmid replication regulation are located on the plasmid rather than on the host chromosome. It is possible therefore that there can be copy-up "cheater" mutants. In spite of this possibility, low copy number plasmids appear to exist stably in host populations. We examined this paradox using a multilevel selection model. Simulations showed that, a slightly higher copy number mutant could out-compete the wild type. Consequently, another mutant with still higher copy number could invade the first invader. However, the realized benefit of increasing intra-host fitness was saturating whereas that of inter-host fitness was exponential. As a result, above a threshold, intra-host selection was overcompensated by inter-host selection and the low copy number wild type plasmid could back invade a very high copy number plasmid. This led to a rock-paper-scissor (RPS) like situation that allowed the coexistence of plasmids with varied copy numbers. Furthermore, another type of cheater that had lost the genes required for conjugation but could hitchhike on a conjugal plasmid, could further reduce the advantage of copy-up mutants. These sociobiological interactions may compliment molecular mechanisms of replication regulation in stabilizing the copy numbers.

Customer service initiatives in healthcare have become a popular way of attempting to improve patient satisfaction. This study investigates the effect of clinically focused customer service training on patient satisfaction in the setting of a 62,000-visit emergency department and level I trauma center. Analysis of patient complaints, patient compliments, and a statistically verified patient-satisfaction survey indicate that (1) all 14 key quality characteristics identified in the survey increased dramatically in the study period; (2) patient complaints decreased by over 70 percent from 2.6 per 1,000 emergency department (ED) visits to 0.6 per 1,000 ED visits following customer service training; and (3) patient compliments increased more than 100 percent from 1.1 per 1,000 ED visits to 2.3 per 1,000 ED visits. The most dramatic improvement in the patient satisfaction survey came in ratings of skill of the emergency physician, likelihood of returning, skill of the emergency department nurse, and overall satisfaction. These results show that clinically focused customer service training improves patient satisfaction and ratings of physician and nurse skill. They also suggest that such training may offer a substantial competitive market advantage, as well as improve the patients' perception of quality and outcome.

The authors adapt the SERVQUAL scale for medical care services and examine it for reliability, dimensionality, and validity in a primary care clinic setting. In addition, they explore the possibility of a link between perceived service quality--and its various dimensions--and a patient's future intent to complain, compliment, repeat purchase, and switch providers. Findings from 159 matched-pair responses indicate that the SERVQUAL scale can be adapted reliably to a clinic setting and that the dimensions of reliability, dependability, and empathy are most predictive of a patient's intent to complain, compliment, repeat purchase, and switch providers.

Application of speckle variance optical coherence tomography (OCT) to endovascular imaging faces difficulty of extensive motion artifacts inherently associated with arterial pulsations in addition to other physiological movements. In this study, we employed a technique involving a fourth order statistical method, kurtosis, operating on the endovascular OCT intensity images to visualize the vasa vasorum of carotid artery in vivo and identify its flow dynamic in a porcine model. The intensity kurtosis technique can distinguish vasa vasorum from the surrounding tissues in the presence of extensive time varying noises and dynamic motions of the arterial wall. Imaging of vasa vasorum and its proliferation, may compliment the growing knowledge of structural endovascular OCT in assessment and treatment of atherosclerosis in coronary and carotid arteries.