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Immunotherapy has changed treatment practices for many hematologic malignancies. Even in the current era of targeted therapy, chemotherapy remains the backbone of treatment for many hematologic malignancies, especially in acute leukemias, where relapse remains the major cause of mortality. Application of novel immunotherapies in hematology attempts to harness the killing power of the immune system against leukemia and lymphoma. Cellular immunotherapy is evolving rapidly for high-risk hematologic disorders. Recent advances include chimeric antigen-receptor T cells, mesenchymal stromal/stem cells, dendritic cell tumor vaccines, cytokine-induced killer cells, and virus-specific T cells. The advantages of nontransplantation cellular immunotherapy include suitability for patients for whom transplantation has failed or is contraindicated, and a potentially less-toxic treatment alternative to transplantation for relapsed/refractory patients. This review examines those emerging cellular immunotherapies that are changing treatment paradigms for patients with hematologic malignancies.

Although ample literature exists regarding the effectiveness of faculty development (FD) activities, there is a gap in the literature synthesizing its outcomes. This review, using a predetermined review protocol, analyzed 22 publications on FD for teacher educators using Kirkpatrick’s training evaluation taxonomy. We found that North American universities provide the most empirical evidence about FD activities, focusing on technology integration in teaching and pedagogical skill improvement. Formal programs, such as serial workshops and developmental relationship, were reported with high frequency, compared to self-directed learning and organizational development activities. Empirical research was heavily based on self-reported, qualitative data and emphasized individual-level outcomes. There is a lack of information regarding the impact of FD activities for teacher educators on subsequent student learning or the downstream effect on school systems. Similarly, institutional involvement in FD remai...

© IWA Publishing 2015. Water businesses have always sought to plan for drought-resilient urban water supply systems, especially in areas with extreme climate variability. The recently completed Lower Hunter Water Plan was developed to support population and business growth, and ensure reliable water supplies in drought. As well as introducing Water Wise Rules to encourage water conservation in normal conditions, the plan identified a portfolio (or combination) of drought response measures to be deployed progressively in a drought as water storage levels drop. The keys to the success of the Plan were thorough consultation with stakeholders, and collaborative analysis facilitating transparent evaluation of trade-offs among options and portfolios. A multi-criteria decision analysis process guided the assessment of the drought response options against both quantitative and qualitative criteria, and the assembly and analysis of portfolios. The process integrated the assessment of social and environmental criteria with cost effectiveness analysis, along with analysis of contextual uncertainties and risks, to determine the resilience of the options under different scenarios. The outcome was a portfolio of drought response options that best met the weighted criteria and satisfied their objectives.

Neonatal diabetes occurs due to a genetic form of pancreatic βcell dysfunction. Mutations in a number of genes have been identified in the last decade which has helped not only in the etiological diagnosis but has also influenced medical therapy. Our proband was born at term with a birth weight of 3.99kg with no antenatal risk factors. He presented in severe diabetic ketoacidosis at 8 weeks which required intensive management. He was commenced on continuous subcutaneous insulin infusion for his ongoing management. His initial genetic analysis for ABCC8, KCNJ11, INS gene mutations was negative. He demonstrated excellent glycaemic control with an average HbA1C of 6.5% at 2 years of age. His growth and development are appropriate for age with no associated co-morbidities. However, further targeted next generation sequencing of all known neonatal diabetes genes identified a hemizygous FOXP3 missense mutation p.R347H with his mother as a carrier. FOXP3 mutations cause IPEX syndrome, (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome) and can be lethal in infancy and early childhood. Prophylactic bone marrow treatment is the only known cure for this condition. Our proband has isolated neonatal diabetes with no other features of IPEX. His maternal grandfather aged 63 years, was also hemizygous for the mutation. He had enteropathy secondary to ulcerative colitis since childhood which was resistant to conventional treatment and required colostomy. This makes him the oldest living man with IPEX. Our proband’s maternal cousin also had eczema in infancy which has resolved. This case highlights the impact of genetic diagnosis on the management of neonatal diabetes. A lethal condition with no cure other than bone marrow transplant has now been shown to have atypical manifestations with the availability of genetic testing. The management in our patient is challenging given the poor genotype – phenotype correlation and the dearth of information regarding milder forms limited to a few case reports with similar mutation. We have decided against prophylactic bone marrow transplant and will consider it in the event of enteropathy or another autoimmune manifestation. Written informed Consent for this patient has been taken including results of the genetic analyses according to the Institutional Ethics Committee procedures of our health service

Objectives The deployment of the UK-led Joint Inter-Agency Taskforce to Sierra Leone in September 2014 brought the era of contingency operations into focus. Daily health screening of such deployed personnel forms a key element of medical force protection. We have performed a service evaluation of an existing screening programme and detail the comparison of the two thermometers used in this role. Methods Data from the existing screening programme were used to inform a sample size required to enable statistically and clinically significant differences to be detected between the two interchangeably used thermometer systems in use. A prospective service evaluation on these devices was then carried out over a 10-day period and the data analysed by parametric tools. 10 personnel had their temperature recorded by both devices at the same time by a single operator every day. Results For the screened population, a mean temperature of 36.55°C and SD of 0.32°C was revealed. Powered to 80% with a two-tailed α of 0.05, the evaluation of the two thermometers revealed no significant difference between recordings taken with either device (p=0.115). The low SD meant that a pyrexial patient (>37.5°C) would require a recording over 3 SD from the population mean. Discussion Evaluations of medical force protection will carry increasing consequence as the UK deploy on short notice operations to regions of considerable endemic threat. Presence of pyrexia is a key early indicator of illness affecting deployed personnel, and two different thermometer types are provided for this function. We have shown for the first time with statistical and clinical significance that the two thermometers used in contingency force protection are interchangeable. The narrow variance is reassuring and confirms that the chosen trigger (>37.5°C) would warrant further investigation in the pyrexial patient.

Editor—Carney and Geddes predict that most parties will be reasonably satisfied with the appraisal of electroconvulsive therapy by the National Institute for Clinical Excellence (NICE).1,2 Our clinical experience is that many patients who may benefit from electroconvulsive therapy will be denied it under these guidelines. Apparently, the NICE appraisal panel did not include a single psychiatrist, which may partly explain why clinical experience of the potential benefits of maintenance electroconvulsive therapy, as described in many reports,3 seems to have been discounted. The recommendations from NICE have also not acknowledged the different potential for memory disruption and cognitive side effects arising from bilateral as opposed to unilateral electroconvulsive therapy.4 Given the concerns about memory disturbance as a side effect of bilateral electroconvulsive therapy, this is a surprising omission. NICE recommends that the use of electroconvulsive therapy in depressive illness should be restricted to patients with severe depressive illness or catatonia in whom an adequate trial of other treatment options has proved ineffective or when the condition is considered to be potentially life threatening.5 In severely depressed patients who have previously shown a good response to electroconvulsive therapy, it may be appropriate to consider it as a first line treatment. The NICE guidelines do not recommend electroconvulsive therapy as a treatment for moderate depressive episodes. As discussed in the response to the appraisal from the Royal College of Psychiatrists' special committee on electroconvulsive therapy and the Scottish electroconvulsive therapy audit network (SEAN),5 the randomised controlled trials that form the evidence base for electroconvulsive therapy were carried out mainly on moderately or moderately severely depressed patients, excluding those with severe depressive episodes who were unable to give informed consent. We consider the NICE guidelines to be unduly restrictive and limiting, encouraging clinicians to deny patients potentially beneficial treatment.

To date, there have been 25 studies attempting to correlate biparietal diameter and gestational age; of these, 17 meet specific criteria and thus are included in this evaluation. Although all studies have shown an increase in biparietal diameter with advancing gestational age, between 17 wk and term there is a discrepancy of approximately 3 wk. In this evaluation the charts are compared and the variations analyzed. An ideal table is constructed by combining the mean gestational age, calculated from a statistical analysis, and the variation at each millimeter point, determined by comparison of all the studies. It is hoped that this new 90% composite table, which consists of a range of gestational ages in weeks for each biparietal diameter, will not only provide more realistic indications of fetal age but also will serve as a reminder to sonographers, obstetricians, and patients of the relative accuracy and variations of biparietal diameter measurements.

A mass containing unusual calcific densities suggestive of bone formation was demonstrated within the breast on xeroradiography. The mass showed a very high uptake of 99mTc-polyphosphate on a total-body radionuclide bone scan and was found to have extensive bone and cartilage formation on pathological examination.

The clinical application of thyroid sonography was not established until 1967 (Fujimoto et al. 1967). This late development is surprising, considering the superficial location of the gland which lies approximately 2 cm below the skin of the anterior neck. But contrary to expectations, it was its superficial location and its size that made early attempts at sonic imaging of the thyroid so difficult. Before water-bath scanning, the standard 2.25 MHz transducers were large-diameter crystals, which when pulsed with an electric current, produced a strong opening bang and a reverberation echo up to 2 cm thick. As a consequence, the thyroid gland was lost within it. Water-bath scanning eliminated this problem, and the tissues immediately below the skin surface could be imaged. Furthermore, the awkwardness resulting from contact scanning of the angular neck contour was eliminated because water-bath scanning allowed easier manipulation of the transducer in the water (Skolnick and Royal 1975).

All ultrasound systems now in routine clinical service utilize only a portion of the information available in an echo waveform. For example, a conventional A-scan displays the intensity of the echo waveform as a function of acoustic travel time and a conventional B-scan produces an ultrasonic mapping in which the spot intensity is proportional to the echo intensity. Phase information (such as the sign or polarity of the echo waveform) is recorded by the transducer, which is a pressure sensitive device, but is not utilized in present display or measurement schemes.

In-vivo attenuation measurements of the liver have been obtained in 41 patients with diffuse liver disease, 8 normal controls and a liver phantom. Using a spectral shift approach, a parameter S (in MHz/cm), the slope of zero-crossings of A-line data vs. depth was measured to estimate the slope of the attenuation coefficient with frequency, denoted by β (in dB/cm-MHz). 1 MByte of digitized data per ultrasound procedure and per liver was used to estimate the slope S. Three different acoustic transducers were used. The patients were classified by histopathological structure following blind readings of liver needle biopsies.

Results of in vivo attenuation measurements in the liver have been obtained in 26 normal controls and in 51 patients with chronic diffuse liver disease. A modified real-time sector scanner was used for narrow-band amplitude attenuation examination. In the control group (people without apparent liver disease), a statistically significant correlation was found between acoustic attenuation in liver and two blood tests reflecting liver function: serum albumin (n = 24, r = 0.67, p = 0.002) and prothrombin time (n = 23, r = 0.63, p = 0.019). There was a statistically significant positive correlation between attenuation and fat for all biopsied patients (n = 51, r = 0.32, p = 0.023) and for patients with minimal fibrosis (n = 25, r = 0.45, p = 0.027). Although no correlation with fibrosis was found for all patients, in the group of patients with minimal fat there was a correlation with portal fibrosis (n = 33, r = 0.37, p = 0.035). This double blind prospective study shows that in the liver: (1) attenuation estimates appear correlated with clinical parameters (blood tests) in normal volunteers, and (2) large changes in fat affect narrow-band acoustic attenuation estimates to a greater degree than severe portal fibrosis in patients with chronic diffuse liver disease. Further research is needed before these estimates can become a clinical tool.

Evaluation of 135 consecutive patients was made for breast masses by the same surgeon and the patients were subsequently referred for ultrasound mammography of the breast after xeromammography revealed a "dysplastic" (DY) pattern only, with no evidence of malignancy. Three patients had carcinoma of the breast detected by ultrasound mammography that had been missed by xeromammography. Two of the three cancers were similarly diagnosed by fine-needle aspiration cytology. All patients with a normal ultrasound examination have now been followed for a minimum of 15 months without evidence of developing breast cancer. This study confirms the importance of using additional diagnostic modalities for evaluating patients with dysplastic breasts and strongly suggests the value of ultrasound mammography in this group of patients.

Of 210 pathologically confirmed palpable breast masses examined by continuous ultrasound B-scanning using a 2.5- or 7-MHz transducer and mammography, fluid filled cysts more than 1 cm in diameter were diagnosed accurately in 75 cases. Of the 103 solid masses studied by echography, 31 were circumscribed (29 benign fibroadenomas and 2 circumscribed medullary carcinomas) and 72 were not. Infiltrating carcinoma represented the majority of the latter type, although 2 cases of chronic inflammation had the same echographic appearance. Thirty palpable breast masses less than 2 cm in diameter were not delineated with the 2.5-MHz transducer, and biopsy showed benign disease. The combination of mammography and continuous ultrasound B-scanning of palpable breast masses improved the diagnostic accuracy obtained with mammography alone and aided in the differentiation of nondiagnostic mammograms.