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Context.—Whole slide imaging (WSI) represents a paradigm shift in pathology, serving as a necessary first step for a wide array of digital tools to enter the field. Its basic function is to digitize glass slides, but its impact on pathology workflows, reproducibility, dissemination of educational material, expansion of service to underprivileged areas, and intrainstitutional and interinstitutional collaboration exemplifies a significant innovative movement with far-reaching effects. Although the benefits of WSI to pathology practices, academic centers, and research institutions are many, the complexities of implementation remain an obstacle to widespread adoption. In the wake of the first regulatory clearance of WSI for primary diagnosis in the United States, some barriers to adoption have fallen. Nevertheless, implementation of WSI remains a difficult prospect for many institutions, especially those with stakeholders unfamiliar with the technologies necessary to implement a system or who cannot effectively communicate to executive leadership and sponsors the benefits of a technology that may lack clear and immediate reimbursement opportunity.Objectives.—To present an overview of WSI technology—present and future—and to demonstrate several immediate applications of WSI that support pathology practice, medical education, research, and collaboration.Data Sources.—Peer-reviewed literature was reviewed by pathologists, scientists, and technologists who have practical knowledge of and experience with WSI.Conclusions.—Implementation of WSI is a multifaceted and inherently multidisciplinary endeavor requiring contributions from pathologists, technologists, and executive leadership. Improved understanding of the current challenges to implementation, as well as the benefits and successes of the technology, can help prospective users identify the best path for success.

William Osler combined many excellent characteristics of a clinical educator being a scientific scholar, a motivational speaker and writer and a proficient physician. As we celebrate his life a century on, many of his educational ideals are as pertinent today as they were in those Victorian times. Osler’s contributions to modern medicine go beyond his legacy of quotable aphorisms to a doctor, educator and leader whose proponent use of bedside teaching, careful clinical methods, and clinicopathological correlation was a great inspiration for students and junior doctors. He was also a great advocate of patient-centred care—listening to and closely observing his patients, an important message for modern medicine as the reliance on investigations strains modern healthcare systems. This review of Osler’s contribution to medical education summarises his development as an educator and provides reflection on his influences to modern clinical education.

Newborn screening (NBS)3 has been acclaimed by the Centers for Disease Control and Prevention as one of the most successful public health programs of the 21st century (1). In 2013, we celebrated the 50th anniversary of NBS, and these 50 years were marked by many successes. An estimated 200 million newborns in the US have been screened during that period for at least 1 disorder, phenylketonuria. Today's screening effort detects >10 000 newborns with certain heritable disorders from the 4 million screened annually. Most of these disorders cause severe, nonreversible harmful effects if not identified and treated before the onset of symptoms (2). NBS programs have evolved as new technologies have been introduced from covering 1 disorder to presently 33 recommended disorders in the US (3, 4). All NBS programs in the US collect blood samples on US Food and Drug Administration–cleared filter paper collection devices (5). Only 2 commercial sources are presently approved for use in device production and dried blood spot (DBS) collection. The filter papers, Whatman Grade 903 and Ahlstrom Grade 226, are made from high-purity cotton linters and manufactured to yield accurate and reproducible blood samples according to the Clinical and Laboratory Standards Institute's specifications (NBS01-A6) (5). Under controlled conditions, the filter paper blood collection device for NBS can achieve the same level of precision and reproducibility expected from clinical methods that typically use blood collected in vacuum tubes or capillary pipettes (6). Unlike these liquid collection devices, filter paper exhibits different levels of imprecision, but these can be characterized and then harmonized to minimize the variation it contributes to measurements (6). Simplicity of collection, transport, and storage makes DBS samples an economical preference for many clinical applications. However, poor-quality filter paper and improperly collected DBS may significantly alter the performance of …

Background The Patient Perception of Patient-Centeredness (PPPC) questionnaire was revised, and there is a need for the questionnaire to be tested in diverse primary care populations. Objectives This study aimed to examine the factor structure of the Revised PPPC questionnaire (PPPC-R) in French-speaking patients with multimorbidity. Design Secondary analysis from baseline data of the French arm of Patient-Centered Innovations for Persons with Multimorbidity Study (PACEinMM Study). Setting and participants Participants were adult patients with multimorbidity attending primary health-care settings. Outcome measures Exploratory factor analyses were applied to examine the factor structure of the PPPC-R. Cronbach's alpha values were calculated to assess the internal consistency of the whole questionnaire and of each factor explored. Results There were 301 participants, mean age 61.0, 53.2% female. The PPPC-R showed very good internal consistency, with three factors: Patient-Centered Clinical Method (PCCM) Component 1-Exploring the health, disease and illness experience + PCCM Component 4-Enhancing the patient-clinician relationship (Factor 1); PCCM Component 2-Understanding the whole person (Factor 2); and PCCM Component 3-Finding common ground (Factor 3). There was a good internal consistency within each factor (Cronbach's α = 0.87 for 8 items in Factor 1, 0.77 for 5 items in Factor 2 and 0.87 for 5 items in Factor 3). Discussion and conclusions The French PPPC-R factor structure was in accordance with the underpinning conceptual model and presented with three factors. Further assessment of its validity and reproducibility are needed to allow its use as a measure of patient's perception of patient-centeredness.

Introduction The morbidity of chronic pancreatitis (CP) remains at a high level. In cases of CP, prepapillary stenosis of the common bile duct (CBD) complicates the course of disease in 30-60% of patients. Aim To improve the detection of biliary hypertension (BH) in patients with complicated forms of CP by increasing the accuracy of preoperative and intraoperative diagnostics using modern diagnostic methods. Material and methods We analysed the results of surgical treatment of 573 patients with complicated forms of CP. In 163 (28.5%) patients, CP was complicated by BH. The method of intraoperative monitoring of biliary pressure (IOM BP) was developed and introduced for intraoperative control and determination of the adequacy of intervention regarding biliary decompression. Results Mechanical jaundice was diagnosed by clinical methods in 101 (61.9%) CP patients with BH, and by laboratory methods in 108 (66.2%) patients. Such methods as magnetic resonance cholangiopancreatography (95.6%), endoscopic retrograde cholangiopancreatography (93.7%), and computed tomography (93.8%) proved to have the highest sensitivity for the diagnostics of BH in cases of CP. Conclusions The application of an integrated approach with extensive use of modern non-invasive preoperative methods of assessment allowed an approximation of the reliability of preoperative diagnostics of BH in CP patients to 95.6%. The use of the IOM BP method enables us to increase the sensitivity of intraoperative diagnostics of BH to 97.3% and choose the method of surgical intervention, which significantly reduces the risk of BH recurrence in the distant postoperative period by 15.1% (χ2 = 4.22, p = 0.04).

Background The ideal gentle cleansing product is one that effectively removes soils while minimizing damage to the skin. Thus, measuring physical abrasion caused by cleansing tissues is critical to the continued development of gentle cleansing products. Current analysis of cleansing materials for skin gentleness is time consuming and requires expensive human subject testing. This report describes the development of a rapid and inexpensive bench assay for the assessment of skin abrasion caused by wiping. Methods Coefficient of friction (COF) evaluations using bench methods were compared with results from clinical studies of repeated wiping and with confocal visualizations of excised skin. A Monitor/Slip and Friction™ instrument (model 32-06; TMI, Amityville, NY, USA) was used to measure tissue friction on simulated skin (Vitro-Skin®, N19-5X; IMS, Milford, CT, USA). Clinical data from a 4-day repetitive forearm wiping study measuring transepidermal water loss (TEWL) in 30 subjects was compared with results from the bench top assay. In addition, excised skin samples were also treated using the COF bench assay and examined using confocal microscopy to visualize stratum corneum damage caused by wiping. Results Using the bench COF assay, we were able to distinguish between bath tissue codes by comparing average static friction value (ASFV) for the test codes, where lower ASFV indicated less abrasive tissue. The ASFV followed the same gentleness trend observed in the clinical study. Confocal microscopy of excised skin wiped with the same materials indicated stratum corneum damage consistent with the bench COF and clinical TEWL observations. Conclusion We observed significant correlation between bench and clinical methods for measuring skin damage caused by wiping of skin with tissue. The bench method will facilitate rapid and inexpensive skin gentleness assessment of cleansing materials.

Purpose The purpose of this article is to describe the appearance of age-related macular degeneration (AMD) phenotypes using infrared (IR) reflectance imaging. IR reflectance imaging of the retina has the potential to highlight specific sub-retinal features and pathology. However, its role in macular disease, specifically AMD, is often underestimated and requires clarification. Recent findings Recent advances in clinical methods, imaging and scientific knowledge may be integrated to improve the accuracy of disease stratification in AMD. In particular, IR imaging holds an underutilised sensitivity to detect reticular pseudodrusen, which have been repeatedly described as a high-risk sign for late AMD. Summary This article provides clinically relevant descriptions of AMD phenotypes using IR reflectance imaging. The findings are integrated with images from cases seen at the Centre for Eye Health. As primary eye-care providers assume a critical role in the detection, diagnosis and management of AMD, we also provide a chair-side reference to assist clinicians in interpreting IR images in AMD.

Coronary heart disease (the presence of coronary atherosclerotic plaques) is a significant health problem in the industrialized world. A clinical method to accurately visualize and characterize atherosclerotic plaques is needed. Intravascular photoacoustic (IVPA) imaging is being developed to fill this role, but questions remain regarding optimal imaging wavelengths. We utilized a Monte Carlo optical model to simulate IVPA excitation in coronary tissues, identifying optimal wavelengths for plaque characterization. Near-infrared wavelengths (≤1800 nm) were simulated, and single- and dual-wavelength data were analyzed for accuracy of plaque characterization. Results indicate light penetration is best in the range of 1050 to 1370 nm, where 5% residual fluence can be achieved at clinically relevant depths of ≥2 mm in arteries. Across the arterial wall, fluence may vary by over 10-fold, confounding plaque characterization. For single-wavelength results, plaque segmentation accuracy peaked at 1210 and 1720 nm, though correlation was poor (

There is general agreement that persistent infection of the urinary tract is a common disease in infancy and childhood, and that, if it is not checked?whether its clinical accompani ments are manifest, silent, or relapsing?it may lead on to chronic atrophie pyelonephritis and hypertensive renal failure (Rosenheim, 1963). The infection may be symptomless, or nearly so, arid evidence from necropsy suggests that by no means all cases are diagnosed before death (Kleeman, Hewitt, and Guze, 1960). Alternatively, symptoms may be ignored or misinterpreted, particularly when they suggest some other disease, as is so frequent in childhood. Though repeated urinary infections are, in fact, usually repeated exacerbations of a continuing underlying process (Deluca, Fisher, and Swenson, 1963), even when this process is suspected, the diagnosis can be difficult to confirm. Now that we have a fuller understanding of its potential seriousness, it is very important not to overlook this infection. The prospects of cure have not in the past been very good (Macaulay and Sutton, 1957 ; Straffon and Engel, 1960), but are getting better as we become aware of correctable surgical lesions that are frequently present at the same time, such as vesico-ureteric reflux (Williams and Sturdy, 1961 ; Gross, Randolph, and Wise, 1963), and now that we possess a new range of antibiotics. In recent years there has been an increasing inclination to rely for diagnosis upon counts of bacteria and white cells in the urine (Kass, 1960 ; Little, 1962 ; Stansfeld, 1962). In the search for accuracy counting techniques have become more complicated, so that dependence on the laboratory has become greater. We still badly need a reliable and simple test that can disclose urinary infection independently of a laboratory, and which is rapid enough to be used with large numbers of patients (Lancet, 1962). A main aim of the study now to be reported was to determine the efficacy of microscoping unspun urine under standard conditions in the ward or out-patient depart ment as a means of detecting infection of the urinary tract. Its further motive was the wish to discover how many of the children treated for acute urinary infection in a hospital unit during the past 12 years had been rendered permanently free of infection.

Increased aldosterone levels with consequent or diuretic-potentiated electrolyte abnormalities are an important consideration when patients with cirrhosis and ascites undergo diuresis. A simple clinical method using the urinary Na/K ratio as a guide to spironolactone dosage is outlined. Patients with a ratio greater than 1 responded well to 100 mg. of spironolactone a day; those when it was one or less responded well to 200 to 1,000 mg. a day.Administration of spironolactone alone (11 patients) or as the main diuretic (three patients) was a safe and effective means of inducing sustained uncomplicated diuresis in all these patients.

This biographical sketch of Nathaniel Allison corresponds to the historic text, The Classic: Symposium on Arthroplasty: Arthroplasty: Experimental and Clinical Methods, available at DOI 10.1007/s11999-009-1120-3 .

Gutta-percha cones were exposed to formocresol vapors for 16 hours to evaluate the antimocrobial action of the agent as a convenient and inexpensive clinical method for cold sterilization of cones. Gutta-percha cones were contaminated with standardized pure cultures of five genera of microorganisms. The cones were exposed subsequently to a closed atmosphere of formocresol vapors for 16 hours. Data from cultures indicated that all microorganisms had been rendered nonviable and remained so throughout the remainder of the five-day period of investigation. These findings indicate that gutta-percha cones may be sterilized by exposure to formocresol vapors in a closed atmosphere.

A method for measuring the urinary levels of 17-OH, 21-methyl corticosteroids is proposed. The principle of the method involves the selective extraction of these compounds from β-glucuronidase hydrolyzed urines with carbon tetrachloride. The routine method for determination of 17-ketogenic steroids is then done on the CCl4 extract. In the presence of significant amounts of 17-KGS, it is possible to distinguish the 17-OH 21-methyl steroids from 17-OH, 20, 21-ketols by performing the Porter-Silber reaction for the latter compounds. The normal levels of total 17-OH, 21-methyl corticosteroids were determined. Elevated levels of total 17-OH 21-methyl steroids were shown in congenital adrenal hyperplasia, and in adult onset virilizing adrenal hyperplasia. Responses to exogenous corticosteroid therapy are also shown. This method is attractive in that it employs the early steps of the routine clinical methods for determination of 17-OH corticosteroids (Porter-Silber chromogens), the modification being the extraction of the 17-OH 21-methyl sterods by CCl4 prior to the methylene dichloride extraction for 17-OHCS. The extraction method is also useful in isolation studies of such steroids.

This paper offers the first examination of Archigenes of Apamea’s use of pain as a diagnostic method. Archigenes claimed that the kind of pain can indicate the affected part in the patient’s body and thus aid in successfully diagnosing and treating the patient. He listed the kinds of pains associated with different organs and used over thirty different terms to qualify pain, among these “numb”, “adherent” and “salty”. Archigenes’ terminology is usually considered incoherent and hence his method impractical. This paper argues that there was a solid foundation guiding Archigenes’ terminology and method. It claims that they rested on an inclusive conception and identification of pain, which took into account other sensations and physical phenomena which the patient was experiencing or the physician himself was observing. In so doing, Archigenes’ method gave the physicians a more active role in identifying and representing patients’ pain and released them from complete dependence on the patients and their subjective and often unreliable pain narratives. Revealing the foundation of Archigenes’ method brings to light an additional manner of conceptualising and narrating pain in the ancient world.

Uterine contractions monitoring is essential during pregnancy progression for due date prediction and the screening of preterm deliveries, i.e., those related to labour contractions occurring before 37 weeks of gestation. As there are different kinds of uterine contraction, distinguishing between true labour ones and normal physiological ones during pregnancy is not trivial. Thus, early identification is necessary for the effective and efficient care of pregnant women to avoid unnecessary and costly hospitalization. In this regard, while classical clinical methods proved their limitations, real-time monitoring of uterine contractions is now possible thanks to a new technique called ElectroHysteroGraphy which measures the uterine electrical activity that is a proxy for the mechanical activity of the muscles of the uterus. An exhaustive and comprehensive literature review was conducted to retrieve and report the state-of-the-art of the methods to distinguish labour contractions from pregnancy contractions. A systematic search was run on different search engines using a search string. A snowball sampling approach was applied to the references of the retrieved articles to identify further appropriate papers. According to this, the relevant references included in the bibliography of each analysed article led to other appropriate articles. Thus, papers dealing with the methods to distinguish labour from pregnancy (normal physiological) contractions and published between 2001 and 2020 were selected. Linear and nonlinear methods have been developed for uterine contractions signals (EHG/EMG) analysis to distinguish labour from pregnancy contractions. Nonlinear methods yielded better results compared to the linear methods, but not all nonlinear methods are promising in terms of clinical application.

Resumo: Neste texto discute-se os critérios utilizados pelas crianças dos anos iniciais referentes à função do acento gráfico no sistema de escrita. Considerando-se a estreita relação entre o acento prosódico e as regras de uso do acento gráfico pretendeu-se investigar as hipóteses das crianças em relação a este dispositivo ortográfico. Os dados analisados foram coletados a partir de um instrumento de escrita controlada criado especialmente para a pesquisa e de entrevistas orientadas pelo método clínico piagetiano (CARRAHER, 1989). Após a produção escrita as crianças foram provocadas, a fim de que explicitassem os motivos pelos quais utilizaram ou não o diacrítico em suas grafias. A análise dos dados de produção escrita mostra que as crianças acertam a grafia do acento preferencialmente nos contextos em que pode ocorrer a alternância de timbre da vogal tônica, ou seja, nas vogais médias e médias baixas. Os resultados das entrevistas apontam para a emergência de critérios baseados em correlatos acústicos e, também, em correlatos gráficos. Foi possível com a análise realizada definir uma hierarquia de critérios acústicos, a saber: timbre vocálico, duração e proeminência acentual. Abstract: This paper discusses the criteria used by third and fifth graders who attend a public school, in Pelotas, RS, Brazil, regarding the function of diacritical marks in the writing system. Considering the close relationship between prosodic stress and the rules of use of diacritical marks, the study reported in this paper aimed at investigating children's hypotheses concerning these orthographic devices. Data were collected by a controlled writing instrument, which was especially designed for this research, and by clinical interviews guided by the Piagetian method (CARRAHER, 1989). After completing a writing task, children were induced to explain the reasons that led them to use diacritics in their spelling. The analysis of data on their written production showed that children got the diacritical mark right, mainly in contexts in which alternation of vowel timbre could occur, that is, in medium and low medium vowels. Results of the interviews highlighted the emergence of criteria based on acoustic and graphic aspects. The analysis allowed us to define a hierarchy of acoustic criteria, i. e., vocalic timbre, vowel duration and prominence.

Enophthalmos has many causes, and serious post-traumatic cases indicate the need for operation. Such diagnoses should be made objectively, and a robust method for quantifying the degree to which the globe has been displaced is key. Current methods of measurement, however, have long been considered unreliable and inconsistent, in particular with regard to interobserver variability. The aim of this paper therefore was to review all these methods systematically, to analyse their reliability, and to compare them with others. The paper also includes a proposed protocol for the accurate and reliable measurement of protrusion of an eye, which aims to standardise the assessment of patients and to create a uniform approach that will enable the selection of those who are most likely to benefit from surgical treatment. Analysis of the data showed that computed tomographic (CT) exophthalmometry is the most reliable, followed by the Mourits' exophthalmometer, which performed better than the other clinical methods. In the acute phase of orbital blowout fractures, the measurement of herniated tissue through a fracture defect may give a good prediction of the degree of enophthalmos that is likely to occur without surgical correction. Measurement of the herniated volume and CT exophthalmometry should be the foundation for diagnosis and the planning of treatment. Three-dimensional imaging or Mourits' exophthalmometers (which are reliable non-radiological methods) could be used in a follow-up protocol.

This paper shows the importance of university extension projects for the effectiveness of sustainable campi to generate benefits for institutions and students from the social and environmental perspective. Having that in mind, the case study used is the role played by Clinica de Direito Ambiental Paulo Nogueira Neto (CPaNN), an environmental law clinic placed at University of Sao Paulo Law School. Initially, it is presented a historical and organizational overview of CPaNN, followed by the demonstration of CPaNN’s most concrete achievements, such as the installation of a bicycle rack in FDUSP’s building and the realization of educational campaigns concerning healthy habits and respect to work environment. Besides that, it concludes by demonstrating the relation between CPaNN’s activities as an example of the importance of activities of Education and Public Outreach and the concretization of more sustainable university spaces. It is perceived that the positivity of these actions accumulate experiences both for their receptors (university itself and individual campaigns targets) and for their actors as well (the students involved). This is an important paper because it illustrates successful cases of sustainability projects within the university; it hopes to offer a model for other institutions, whilst being open to discussion and yearning for improvement. The method used is descriptive-inductive with exploratory goals, using the authors’ own experience as the source of most of the information presented.

The bone age of a child indicates the skeletal and biological maturity of an individual. The most commonly applied clinical methods for Bone Age Assessment (BAA) are based on the visual examination of ossification of individual bones in radiographs of the left hand and the wrist by comparing with standard hand atlas. This kind of method is highly subjective and the performance extremely depends on practitioners' experiences. This paper investigates the use of Deep Convolutional Neural Networks (DCNNs) for the automatic bone age assessment. As there exists no large-scale annotated medical image dataset comparable to ImageNet for medical image analysis, this paper uses transfer learning within DCNNs to perform bone age classifications making full use of advantages of DCNNs. We define various Regions of Interest (ROIs) based on domain knowledge, for each of which a local bone age classification model is achieved by fine-tuning the pre-trained VGGNet with corresponding ROI patches. A final bone age classification is obtained by fusing multiple regional models. The results show that the proposed approach outperforms the current state-of-the-art classification methods in BAA with small dataset.

Although many studies have focused on the preoperative risk factors of anastomotic leakage after colorectal surgery (CAL), postoperative delay in diagnosis is common and harmful. This review provides a systematic overview of all available literature on diagnostic tools used for CAL. A systematic search of literature was undertaken using Medline, Embase, Cochrane and Web-of-Science libraries. Articles were selected when a diagnostic or prediction tool for CAL was described and tested. Two reviewers separately assessed the eligibility and level of evidence of the papers. Sixty-nine articles were selected (clinical methods: 11, laboratory tests: 12, drain fluid analysis: 12, intraoperative techniques: 22, radiology: 16). Clinical scoring leads to early awareness of probability of CAL and reduces delay of diagnosis. C-reactive protein measurement at postoperative day 3-4 is helpful. CAL patients are characterized by elevated cytokine levels in drain fluid in the very early postoperative phase in CAL patients. Intraoperative testing using the air leak test allows intraoperative repair of the anastomosis. Routine contrast enema is not recommended. If CAL is clinically suspected, rectal contrast-computer tomography is recommended by a few studies. In many studies a "no-test" control group was lacking, furthermore no golden standard for CAL is available. These two factors contributed to a relatively low level of evidence in the majority of the papers. This paper provides a systematic overview of literature on the available tools for diagnosing CAL. The study shows that colorectal surgery patients could benefit from some diagnostic interventions that can easily be performed in daily postoperative care.

In this paper, a design method for optimal cancer chemotherapy schedules via genetic algorithm (GA) is presented. The design targets the key objective of chemotherapy to minimize the size of cancer tumor after a predefined time with keeping toxic side effects in limit. This is a difficult target to achieve using conventional clinical methods due to poor therapeutic indices of existing anti-cancer drugs. Moreover, there are clinical limitations in treatment administration to maintain continuous treatment. Besides, carefully decided rest periods are recommended to for patient’s comfort. Three intermittent drug scheduling schemes are presented in this paper where GA is used to optimize the dose quantities and timings by satisfying several treatment constraints. All three schemes are found to be effective in total elimination of cancer tumor after an agreed treatment length. The number of cancer cells is found zero at the end of the treatment for all three cases with tolerable toxicity. Finally, two of the schemes, “Fixed interval variable dose (FIVD) and “Periodic dose” that are periodic in characteristic have been emphasized due to their additional simplicity in administration along with friendliness to patients. responses to the designed treatment schedules. Therefore the proposed design method is capable of planning effective, simple, patient friendly and acceptable chemotherapy schedules.

This paper begins with a review of the scientific and technical problems that led Freud to abandon neuroscience and to establish the new discipline of psychoanalysis. That review is followed by a consideration of some developments that took place in the neurosciences after Freud's death, due to the efforts of the Soviet neurologist, A.R. Luria. These developments seem to reverse the historical justification for an ongoing separation between psychoanalysis and neuroscience. Luria's early involvement with psychoanalysis is then described in detail, and its possible influence on his neuropsychological work is considered. The paper ends with the suggestion that a reintegration of psychoanalysis with the neurosciences is now possible, due to the fact that Luria has addressed all the major neuroscientific problems that Freud identified as the stumbling blocks to a viable neurological understanding of mental functioning. A methodological proposal for future neuro-psychoanalytical interdisciplinary research is advanced on the basis of these historical considerations. In this paper I want to show how knowledge of the history (and prehistory) of our discipline can sometimes contribute to the solution of contemporary scientific problems of practical importance.

Formal and functional approaches to pragmatics are based upon different assumptions about the nature of the language system. This paper examines these approaches to pragmatics and considers how each approach has been applied to understand the different language disorders that emerge from left and right brain-damage. The paper explores conflicting reports in the literature about pragmatic performance and hemispheric side of lesion. Finally, clinical methods based on both the formal and functional approaches to pragmatics are discussed.

Human voice as well as the sound of the body is used as a clinical method to assess the health condition of an individual. The evaluation of the human voice has risen as a critical field of exploration. Speech analysis fundamentally involves the extraction of certain features from voice signals for generation of voice in alluring pertinence by using reasonable techniques. This paper brings up normal ailments that sway understanding voice patterns in proof for driving research that have affirmed voice modifications as demonstrative manifestations in their respective ailments and also the technique by which voice analysis can be done.

The presence of large number of modern methods (devices and papers published discussing issues and challenges with existing methodology) for the determination of bilirubin in the blood (plasma) indicates the difficulties of estimation and suggests the need for simpler yet reliable method. Also hospital turn-around time between obtaining a blood sample and receiving results from a central clinical laboratory often slows the pediatrician's management of healthy and hyperbilirubinemic neonates and results in delaying the discharge of mother and child from the hospital thereby increasing the healthcare cost. Furthermore, the most frequent cause of hospital readmissions for the neonates is due to rebound jaundice caused due to inefficient assessment of the hyperbilirubinemia. In view of the importance of bilirubin levels in the diagnosis and treatment of neonatal jaundice, a portable bilirubinometer with accuracy similar to clinical method of evaluation is needed. This paper provides the outcome of the research groundwork (literature & product survey) and technical output (system design, experimental setup, results) in realizing a point-of-care bilirubinometer based on the serum analysis.

This paper introduces a new, clinical-developmental approach to research, theory and intervention. A line of research is described exploring the relationship between developmental organizations of meaning and symptom expression in adolescence. These cross-sectional and longitudinal studies demonstrate needed distinctions between self-complexity and self-maturity/integration—concepts that are described in the context of an overarching framework. In the final section of the paper, clinical methods are introduced for different adolescent developmental worlds and are exemplified with two cases.

Chagas disease is one of the most important parasitic diseases transmitted to animals and people by insect vectors. According to the World Health Organization, around seven million people were infected with Trypanosoma cruzi (also known as kissing bug) that causes Chagas disease. As kissing bugs belong to different families with different danger levels, accurate classifications of kissing bugs species would help the public authorities create a controlled surveillance system. Clinical methods for detecting kissing bugs are expensive, time-consuming, and need a high level of expertise. To overcome these limitations, computational methods can be used. In this paper, a fully automated deep learning model using a convolutional neural network (CNN) with a fine-tuned transfer learning model is proposed to identify kissing versus non-kissing bugs and classify the type of kissing bug species. The accuracy of 99.45% for the classifications of kissing vs. non-kissing bugs and 96% for the classifications of different kissing bugs species is achieved. Finally, a web application is developed based on the proposed model to help the community collecting and identifying kissing bugs species.

Experimental sciences rely on technical methods. In the case of clinical pharmacology, methods are often used that have been developed by other disciplines, such as analytical chemistry (eg high performance liquid chromatography, gas chromatography, mass spectrometry), biochemistry/molecular biology (eg radioimmunoassay/ELISA, Southern/western blotting, PCR/DNA sequencing), physiology (functional surrogates such as blood pressure, forced expiratory volume in 1 second and specific airway conduction), psychology (subjective states such as drowsiness and mood and objective measurements such as reaction times), statistics (eg population PK-PD analyses), epidemiology (eg survival), economics (quality-adjusted life-years) and so on. However, measuring drug effects in man presents distinct challenges and as we have mentioned previously [1], we propose to publish in the Journal a new series of methods papers that review what can be done to measure different kinds of drug effects using contemporary methods. Meanwhile, several of the papers published in this issue illustrate the broad role of clinical pharmacology as a source of tools, both in translational medicine [2] and in the wider field of pharmacoepidemiology. An underlying theme is the usefulness of related research at adjacent levels of biological scale and complexity, for example cellular-organ, organ-intact human, individual patient-exposed population.

This paper considers issues relating to professional legal education and clinical legal education. It provides a brief overview of the history of clinical legal education in the United States and in England and Wales. It considers law school identity, the theory and context of professional education and professional work, the analysis of what lawyers do, and the distinctions between a “competencies approach” and a “reflective practitioner approach”. The paper goes on to ask whether clinic was a creature of its time and then considers “evidence-based practice” as a means of building a collaboration of academics and practitioners for the training of lawyers.

Development of a chromatographic method in bioanalysis is a challenging and complex procedure with many pitfalls and often unexpected reversals that can require several months to accomplish. Even an experienced analytical team must contend many limitations mainly in connection with the strict requirements imposed on current clinical research. These restrictions typically persist throughout the whole development process, from clinical trial assignment, across optimization of extraction of biological materials and chromatographic separation, to validation and data interpretation. This paper describes questions and their possible answers raised during the pre-analytical phase such as use of modern sample preparation techniques in clinical methods, application of internal standards, as well as selection of stationary phases and detection techniques in the analytical phase. Validation problems and interpretation of results are demonstrated with three typical examples of characteristics to be considered, i.e. recovery, matrix effect, and limit of detection vs. lower limit of quantification.

The current paper introduces a clinical method for experience-near interpretation of transference patterns taking place in the symptom context. This research is a qualitative metasynthetic study. The method of Luborsky’s Core Conflictual Relationship Themes was conducted here on 33 transference case studies published in peer-reviewed journals and sourced from an appropriate database. Case components were categorized and relationships between them were analyzed using the method of Relationship Between Categories. We found that transferential components observed in the context of the symptom were a powerful source of distress. These components were found to be interlinked in patterns of two, three or four core categories. Based on these findings we suggest a therapeutic method that enhances self-understanding and maps out milestones for change. The suggested method is sensitive to a set of the patients’ covert associations, which thus becomes a key to undermining the unconscious balance between healthy and pathologic urges.

Balance is the ability to maintain equilibrium while sitting or standing. There are a number of different methods which are used to assess balance: technical methods such as sway magnetometry, ataxia meter and force platforms, and clinical methods such as the functional reach test, Berg balance test and fall risk index. The most frequently used technical method is the force platform. There are two types of force platform, a static and a dynamic force platform, of which the dynamic force platform has been found to be more sensitive to detect impaired balance. The quantitative posturography system (QPS) described in this paper is a type of dynamic force platform; however, it has a simpler design than the currently available dynamic force platforms and can match the subject's sway exactly for tilting in the anterio-posterior and medio-lateral directions with its novel design. This paper describes the novel design of the QPS and its calibration.

Pressure injury (PI) is a major problem for patients that are bound to a wheelchair or bed, such as seniors or people with spinal cord injuries. This condition can be life threatening in its later stages. It can be very costly to the healthcare system as well. Fortunately with proper monitoring and assessment, PI development can be prevented. The major factor that causes PI is prolonged interface pressure between the body and the support surface. A possible solution to reduce the chance of developing PI is changing the patient’s in-bed pose at appropriate times. Monitoring in-bed pressure can help healthcare providers to locate high-pressure areas, and remove or minimize pressure on those regions. The current clinical method of interface pressure monitoring is limited by periodic snapshot assessments, without longitudinal measurements and analysis. In this paper we propose a pressure signal analysis pipeline to automatically eliminate external artefacts from pressure data, estimate a person’s pose, and locate and track high-risk regions over time so that necessary attention can be provided.

Women with metastatic breast cancer (MBC) face serious physiological and psychosocial challenges. The management of this chronic, incurable condition requires long-term care coordination. Traditional clinical methods do not often provide adequate and personalized support for these individuals. In this project, we aim to use smart speakers to provide supportive care interventions to improve the quality of life for women with MBC. Specifically, we have developed Nurse AMIE (Addressing Metastatic Individuals Everyday) by leveraging the Amazon Alexa to remotely deliver validated interventions. We believe that voice interactions can significantly lower the barrier to interact with remote intervention technologies for this population. In a pilot study, we deployed Nurse AMIE for 14 days over 6 women with MBC. Based on the collected data, this paper discusses the feasibility, acceptability, and future directions of Nurse AMIE. To the best of our knowledge, this is the first study to use smart speakers to support women with MBC.

Suicide is a critical issue in modern society. Early detection and prevention of suicide attempts should be addressed to save people's life. Current suicidal ideation detection methods include clinical methods based on the interaction between social workers or experts and the targeted individuals and machine learning techniques with feature engineering or deep learning for automatic detection based on online social contents. This paper is the first survey that comprehensively introduces and discusses the methods from these categories. Domain-specific applications of suicidal ideation detection are reviewed according to their data sources, i.e., questionnaires, electronic health records, suicide notes, and online user content. Several specific tasks and datasets are introduced and summarized to facilitate further research. Finally, we summarize the limitations of current work and provide an outlook of further research directions., IEEE Transactions on Computational Social Systems

The advancement in the materials manufacturing at micrometer and nanometer scales has already enabled numerous applications in electronics, optics, chemistry, biology and medicine. Biomedical devices carrying micro-/nanostructures are currently being widely used in drug delivery, drug release, biosensing and therapy. New clinical methods for disease diagnosis and treatments are being developed enabled by nanotechnology. One-dimensional (1D) structures are playing an important role in the direct drug delivery both in vivo and ex vivo among various micro-/nanostructures. Here, in this paper, we reviewed recent progresses made on next-generation intradermal and intracellular delivery strategies and applications with focus on 1D microstructure-based approaches.

Liver cancer is the common malignant tumor in China and current treatment is based on surgery. However, liver function of many liver cancer patients is impaired before surgery, so there’s a high possibility of occurrence of liver failure after the tumor resection. Therefore, it’s necessary to accurately evaluate liver function before surgery. Currently, clinical methods are mostly limited to assess the function of overall liver. But the application of hepatocyte-specific contrast agent—gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) makes it possible to assess the function of local liver segment accurately. This paper reviewed the progress of using Gd-EOB-DTPA dynamic contrast enhanced magnetic resonance imaging (MRI) to assess liver function preoperatively, such as parameters selection for liver function assessment, clinical factors affecting Gd-EOB-DTPA enhanced MRI and so on.