To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The bone marrow (BM) is a frequent site of haematogenous spread for all types of cancer. Metastatic spread of disseminated tumour cells (DTCs) to the BM is detected in 0.2 to 12% of patients with solid tumours . The variability in incidence is related to the incidence of the primary tumour and its homing behaviour . Common primary tumours affecting the BM are listed below (Table 17.1).
Immunophenotyping is an important part of the integrated haematopathologic diagnostics of bone marrow (BM) samples. Integrated diagnosis should include clinical information, peripheral blood (PB) and BM smear cytology, flow cytometry (FCM) of BM aspirate, BM trephine biopsy (BMB) morphology, BMB immunohistochemistry (IHC) and cytogenetic/molecular genetic data if appropriate. Flow cytometry and IHC provide complementary information . Immunophenotyping by FCM has the advantage of measuring high numbers of cells and the possibility to evaluate co-expression of several markers in various cell populations in a multicolour setting. Immunohistochemistry provides a possibility of in situ interpretation of morphology and immunophenotype simultaneously. Double IHC stains are possible but not widely used as of yet.
The Innovation Pyramid, like any tool, comes down to how well we learn to use it to improve our collective judgement. Reviewing innovation projects allows us to better understand the linkages between the specific-level decisions and the overall project outcome. This deeper discernment requires a critical analysis of the entire innovation system – every decision taken between the initial situation and overall desired outcome must be reviewed. Fortunately, the structure of The Innovation Pyramid is equally useful in guiding the identification of the well-rationalized choice made during the design and execution of the innovation that inadvertently caused us to veer away from our overall, macro-level, desired impact of the original situation. This chapter lays out a structure to systematically review the project elements that could be associated with the variance between the actual and forecasted impact of the innovation. The guidance that The Pyramid provides for a project's post-execution review must often be augmented with additional research. Firms should consider this additional research an investment in their emerging core competency of serial innovation.
Acute myeloid leukaemia (AML) is a highly complex and heterogeneous disease. Proper classification according to the 2016 World Health Organization (WHO) classification requires a systematic approach and integration of key clinical, laboratory, pathologic and genetic information [1, 2]. Great advances in our understanding of the pathogenesis and molecular underpinnings of AML have been realized since the original AML classification using the French–American–British (FAB) system (1976). This genetic revolution not only contributes to enhanced disease diagnosis and prognostication but also to ongoing improvements in therapeutic strategies.
The Innovation Pyramid is an inverted triangular pyramid. The methodology for creating impactful solutions to real problems separates the innovation's design from its execution. It further bifurcates design into identifying the real problem before crafting a solution to it. Execution is similarly bifurcated into execution planning and implementation. The four stacked levels of The Innovation Pyramid, from top to bottom, represent Problem Identification, Solution Formulation, Planning and Implementation; two design stages followed by two execution stages. The Pyramid has three faces. These three pyramid sections address three different aspects of designing and executing impactful solutions:
What: What is the desired outcome at that level?
How: How will this be accomplished or enabled?
Who: Who will lead the activities and/or is impacted by the outcome of this level?
This structure streamlines innovation creation as well as providing a structural means for diagnosing the cause of the variance between the actual and forecasted impact of the innovation. This diagnostic aspect is especially important when we may be traversing The Innovation Pyramid structure multiple times, once for say, prototype development, and a second time for the final product launch.
Mycobacterial infections are widely distributed in animals and cause considerable economic losses, especially in livestock animals. Bovine paratuberculosis and bovine tuberculosis, which are representative mycobacterial infections in cattle, are difficult to diagnose using current-generation diagnostics due to their relatively long incubation periods. Thus, alternative diagnostic tools are needed for the detection of mycobacterial infections in cattle. A biomarker is an indicator present in biological fluids that reflects the biological state of an individual during the progression of a specific disease. Therefore, biomarkers are considered a potential diagnostic tool for various diseases. Recently, the number of studies investigating biomarkers as tools for diagnosing mycobacterial infections has increased. In human medicine, many diagnostic biomarkers have been developed and applied in clinical practice. In veterinary medicine, however, many such developments are still in the early stages. In this review, we summarize the current progress in biomarker research related to the development of diagnostic biomarkers for mycobacterial infections in cattle.
This foreword frames the Symposium in two ways. It summarises the core themes running through the nine ‘meditations’ in The Status of Law in World Society. Moreover, it places these themes in the wider context of Kratochwil's critical engagement with how we pursue knowledge of and in the social world and translate this knowledge into action. Ultimately, also his pragmatic approach cannot escape the tensions between theory and practice. Instead, we are in the midst of both.
With the exception of near-occlusion, CEA is of overall benefit for selected patients with recent symptomatic carotid stenosis =50% (NASCET method), provided surgical stroke/death risk is low. The benefit is greater with greater stenosis, men, the elderly (aged =75y), most recent ischaemic event within 2w, irregular plaque surface, and impaired cerebral perfusion reserve. Patients with recent symptomatic carotid territory ischaemic events should be screened by Doppler ultrasonography, MRA, or CTA, confirming substantial stenosis with a second non-invasive investigation. Catheter angiography may be required to confirm uncertain results. The surgical peri-operative stroke and death rate (7% in RCTs) is higher in women, hypertension, peripheral arterial disease, and occlusion of the contralateral ICA or ipsilateral ECA. The experience of the surgeon and hospital are crucial, and audited peri-operative complication rates should be publically available. Carotid stenting is less invasive than CEA and causes fewer local complications (cranial neuropathy and neck haematoma), but carries a higher procedural risk of stroke. Stenting should be considered in younger patients, or those at increased risk from CEA. While stenting is of high risk for intracranial vertebral artery stenosis, risk is low for extracranial stenosis and should be considered for recurrent symptoms despite optimal medical therapy.
Aneurysmal SAH is a severe disease, and the post-haemorrhage period fraught with potential complications that must be recognized and treated early for favourable outcome. While diagnosis of SAH is often straightforward from clinical history and initial CT, some patients will require cerebrospinal fluid evaluation. The aneurysm must be secured urgently to reduce rerupture and clinical worsening. Endovascular coiling is preferable when feasible, but surgical clipping is sometimes needed based on patient or aneurysmal characteristics, or presence of intraparenchymal haemorrhage requiring evacuation. Treatment of symptomatic hydrocephalus with CSF diversion is also crucial. Patients with aneurysmal SAH should be managed by a team of nurses and physicians with neurocritical care, neuroendovascular, and neurosurgical expertise, preferably in a dedicated neurosciences intensive care unit. Early complications include aneurysmal rebleeding, hydrocephalus, and neurogenic cardiopulmonary injury. In the subacute phase, delayed cerebral ischaemia and hyponatremia are more commonly seen. With optimal multidisciplinary management, many patients can return to their previous level of function only weeks after the aneurysm rupture. Still, most treatments in SAH are based on insufficient evidence, and more collaborative research from the bench to the bedside is necessary to continue improving patient outcomes.
This study aimed to evaluate the performance of the point-of-care circulating cathodic antigen (POC-CCA) test in a highly endemic area in Brazil, comparing it to the Kato-Katz (KK) technique for sensitivity, specificity and the intensity of the reaction of the test in relation to the parasitic load. The community in Sergipe, Brazil, participated in the study, providing three stool samples, one of urine (POC-CCA) and fingers tick blood sample was tested by enzyme-linked immunosorbent assay (ELISA). Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, kappa coefficient and Spearman's correlation were calculated for the POC-CCA test using the KK as the reference. The prevalence of schistosomiasis by KK testing was 48.82%; POC-CCA (t+) 66.14%; POC-CCA (t−) 45.24%. ELISA results showed 100% agreement in individuals with high and moderate eggs per gram (EPG). POC-CCA presented good diagnostic performance in individuals with medium and high EPG, but there were a high number of false negatives in individuals with low intensity infections. As observed, POC-CCA-filter test improves accuracy and sensitivity compared to a conventional test.
As the COVID-19 pandemic continues to escalate and place pressure on hospital system resources, a proper screening and risk stratification score is essential. We aimed to develop a risk score to identify patients with increased risk of COVID-19, allowing proper identification and allocation of limited resources. A retrospective study was conducted of 338 patients who were admitted to the hospital from the emergency room to regular floors and tested for COVID-19 at an acute care hospital in the Metropolitan Washington D.C. area. The dataset was split into development and validation sets with a ratio of 6:4. Demographics, presenting symptoms, sick contact, triage vital signs, initial laboratory and chest X-ray results were analysed to develop a prediction model for COVID-19 diagnosis. Multivariable logistic regression was performed in a stepwise fashion to develop a prediction model, and a scoring system was created based on the coefficients of the final model. Among 338 patients admitted to the hospital from the emergency room, 136 (40.2%) patients tested positive for COVID-19 and 202 (59.8%) patients tested negative. Sick contact with suspected or confirmed COVID-19 case (3 points), nursing facility residence (3 points), constitutional symptom (1 point), respiratory symptom (1 point), gastrointestinal symptom (1 point), obesity (1 point), hypoxia at triage (1 point) and leucocytosis (−1 point) were included in the prediction score. A risk score for COVID-19 diagnosis achieved area under the receiver operating characteristic curve of 0.87 (95% confidence interval (CI) 0.82–0.92) in the development dataset and 0.85 (95% CI 0.78–0.92) in the validation dataset. A risk prediction score for COVID-19 can be used as a supplemental tool to assist clinical decision to triage, test and quarantine patients admitted to the hospital from the emergency room.
Psychiatrists may be daunted by the prospect of undertaking a neurological examination. In this article we briefly review the neurological signs that may be seen in the context of some common neurological disorders of cognition and movement which may present with neurobehavioural symptoms and therefore may be seen initially by psychiatrists. This approach emphasises that neurological examination is not simply an operationalised procedure but an interpretative process. We propose a minimum neurological examination suitable for use by psychiatrists. Many of the signs included are relatively simple to observe or elicit, require no special equipment, and the examination techniques involved are easy to master.
Less than half of postnatal depression cases are identified in routine clinical assessment. Guidelines and current literature suggest that general practitioners (GPs) may have an opportunistic role in detecting postnatal depression due to their early contact and existing rapport with many new mothers. There is limited research on the diagnostic approaches chosen by GPs in different GP−patient contexts. Our small-scale study evaluates the thought processes of seven GPs based in one practice when forming a clinical diagnosis of postnatal depression under different contexts.
Seven GP participants were interviewed using case vignettes about postnatal depression, based on an adapted Johari’s window framework. A realist approach to analysis was undertaken with the intention of understanding GPs’ responses to different situations. Context−mechanism−outcome configurations were constructed, and a programme theory was formed to consolidate the findings.
Findings suggest that diagnoses may be a clinician-led or collaborative process between GP and patient. In collaborative contexts, stigmatising views were addressed by GPs, time for self-reflection was encouraged and mothers’ views were accounted for. Clinician-led diagnoses often occurred in contexts where there was a lack of acknowledgement of symptoms on behalf of the patient or where safety was a concern. The personal and clinical experience of GPs themselves, as well as effective communication channels with other primary care professionals, was significant mechanisms.
GPs use a variety of strategies to support patient disclosure and acceptance of their condition. The complexity of GP−patient contexts may influence the clinical thought process. We address some of the gaps in existing literature by exploring postnatal depression diagnosis in primary care and provide tentative explanations to suggest what works, for whom and in what contexts.
We provide a brief account of the life and work of Jules Parrot, a significant figure in French paediatrics, about whom almost nothing has been written. We focus on his work relating to congenital syphilis, specifically reporting on the examination of a collection of bones taken at autopsy from children with congenital syphilis. The collection of bones was brought to London in 1879 by Parrot to illustrate a talk that he gave before the Pathological Society of London. Subsequently, it travelled a circuitous route to the Royal Free Hospital pathology collection, where it remained until we (GC and TW) ‘discovered’ it. The bones represent the largest assemblage of material from cases of congenital syphilis in the UK and they are important as they clearly demonstrate the skeletal lesions associated with congenital syphilis and are now irreplaceable. The bones have been identified to anatomical element and have come from a minimum of eight children, both foetuses and neonates covering the period 30–50 weeks post-conception. Radiological and micro computerised tomography examinations were carried out and three-dimensional models printed at twice life size. The models are durable and can be handled with impunity by students and others wishing to familiarise themselves with the skeletal changes shown.
Free-living amoeba of the genus Acanthamoeba are ubiquitous protozoa involved in opportunistic and non-opportunistic infection in humans, such as granulomatous amoebic encephalitis and amoebic keratitis. Both infections have challenging characteristics such as the formation of the resistant cysts in infected tissues, hampering the treatment and most usual diagnosis depending on time-consuming and/or low sensitivity techniques. The use of monoclonal antibodies presents itself as an opportunity for the development of more effective alternative diagnostic methods, as well as an important and useful tool in the search for new therapeutic targets. This study investigated the possibility of using a previously produced monoclonal antibody (mAb3), as a diagnostic tool for the detection of Acanthamoeba trophozoites by direct and indirect flow cytometry and immunofluorescence. Immunoprecipitation assay and mass spectrometry allowed the isolation of the antibody's target and suggested it is a transporter part of the CPA (cation: proton antiporter) superfamily. In vitro tests indicate an important role of this target in Acanthamoeba's encystment physiology. Our results support the importance of studying the role of CPA2 transporters in the context of acanthamoebiasis, as this may be a way to identify new therapeutic candidates.
The validity of studies on the diagnostic significance of first-rank symptoms (FRS) for schizophrenia has been put in doubt because of a poor compliance with Schneider's criterion for their definition and the lack of use of the phenomenological method for their assessment. In this study, using a rigorously phenomenological approach to elicit FRS, we examined (a) the degree to which unequivocally present FRS differentiated schizophrenia (n=513) from other psychotic disorders (n=633), and (b) the comparative validity between FRS and other reality-distortion symptoms against 16 external validators in the whole sample of psychotic disorders (n=1146). Diagnostic performance indices (with 95% CIs) of FRS for diagnosing schizophrenia were as follows: sensitivity=0.58 (0.54−0.61), specificity=0.65 (0.62−0.67), positive predictive value=0.57 (0.54−0.60) and negative predictive value=0.65 (0.63−0.68). While the overall association pattern of FRS and non-FRS scores with the validators was rather similar, three validators (premorbid social adjustment, number of hospitalizations and global assessment of functioning) were significantly related to non-FRS scores (p < 0.006) but not to FRS scores (p > 0.05). Furthermore, no validator was significantly related to FRS scores and unrelated to non-FRS scores, all of which indicates an overall better predictive validity for non-FRS delusions and hallucinations. These findings suggest that FRS do not have diagnostic value for diagnosing schizophrenia and that they do not meaningfully add to the external validity showed by other delusions and hallucinations. We believe that much of the misunderstanding about the diagnostic and clinical validity of FRS for schizophrenia is rooted in Schneider's confusing concept of the disorder.
Two articles on the potential impact of the current coronavirus pandemic on psychiatry reveal agreement on many points, but opposing positions on the methodology, philosophy and politics of psychiatry's response. This points to the need for psychiatry to audit its approach to evidence when agility is required.
The COVID-19 pandemic has led to predictions of a widespread mental health crisis. However, this makes little sense when fear and anxiety are so understandable in context. The individualisation and medicalisation of normal human reactions disconnects us from our feelings and from the appropriate solutions, in relation to the pandemic and more generally. We have an opportunity to challenge this pervasive way of thinking, and thus be in a position to create a fairer society that is better for everyone's emotional well-being.
While early diagnosis of younger-onset dementia (YOD) is crucial in terms of accessing appropriate services and future planning, diagnostic delays are common. This study aims to identify predictors of delay to diagnosis in a large sample of people with YOD and to investigate the impact of a specialist YOD service on this time to diagnosis.
A retrospective cross-sectional study.
The inpatient unit of a tertiary neuropsychiatry service in metropolitan Victoria, Australia.
People diagnosed with a YOD.
Measurements and methods:
We investigated the following predictors using general linear modeling: demographics including sex and location, age at onset, dementia type, cognition, psychiatric diagnosis, and number of services consulted with prior to diagnosis.
A total of 242 inpatients were included. The mean time to diagnosis was 3.4 years. Significant predictors of delay included younger age at onset, dementia type other than Alzheimer’s disease (AD) and behavioral-variant frontotemporal dementia (bvFTD), and increased number of services consulted. These predictors individually led to an increased diagnostic delay of approximately 19 days, 5 months, and 6 months, respectively. A specialized YOD service reduced time to diagnosis by 12 months.
We found that younger age at onset, having a dementia which was not the most commonly occurring AD or bvFTD, and increasing number of services were significant predictors of diagnostic delay. A novel result was that a specialist YOD service may decrease diagnostic delay, highlighting the importance of such as service in reducing time to diagnosis as well as providing post-diagnostic support.
Different countries have adopted strategies for the early detection of SARS-CoV-2 since the declaration of community transmission by the World Health Organization (WHO) and timely diagnosis has been considered one of the major obstacles for surveillance and healthcare. Here, we report the increase of the number of laboratories to COVID-19 diagnosis in Brazil. Our results demonstrate an increase and decentralisation of certified laboratories, which does not match the much higher increase in the number of COVID-19 cases. Also, it becomes clear that laboratories are irregularly distributed over the country, with a concentration in the most developed state, São Paulo.