A novel approach to 3D modelling ground-penetrating radar (GPR) data - A case study of a cemetery and applications for criminal investigation.

Ground-penetrating radar (GPR) is an established geophysical technique used extensively for the accurate reconstruction of the shallow (<10 m) subsurface. Reconstructions have largely been completed and presented as 2D vertical and horizontal planes, leaving limited visualization of subsurface 3D shapes and their spatial relationships. With technological advancements, particularly the availability and integration of various software platforms, 3D modelling of GPR data is now emerging as the new standard. However, despite these developments, there remains an inadequate examination and testing of these techniques, particularly in determining if their application is beneficial and warranted. In this study we conducted a GPR grid survey on a churchyard cemetery to generate and evaluate 2D and 3D-modelled reconstructions of the cemetery burial sites. Data collection and processing was completed using a Sensors and Software Incorporated pulseEKKO™ Pro SmartCart GPR system and EKKO_Project™ software, respectively. The modelling component was achieved using Schlumberger's Petrel™ E & P software platform, which is tailored to the petroleum industry. The subsurface patterns present in the 2D and 3D models closely matched the cemetery plot plan, validating our data collection, processing, and modelling methods. Both models were adequate for 2D horizontal visualization of reflection patterns at any specific depth. The 3D model was used to identify the presence of a companion burial plot (stacked caskets) and possible leachate plumes below and encircling burial sites, both of which were not evident in the 2D model, highlighting the benefits of 3D modelling when discerning subsurface objects. We expect our findings to be of value to similar GPR studies, with particular significance to geoforensic studies and criminal investigations.

Post-relapse survival after haploidentical transplantation vs matched-related or matched-unrelated hematopoietic cell transplantation.

Relapse remains a major cause of mortality among patients receiving allogeneic hematopoietic cell transplantation (HCT). The impact of donor type on post-relapse survival (PRS) has not been widely examined. We compared the survival outcomes for patients relapsing after haploidentical donor transplantation (HIDT) using post-transplant cyclophosphamide with those relapsing after matched-related donor transplantation (MRDT) or matched-unrelated donor transplantation (MUDT) at our institution. Two hundred and thirty-seven consecutive HCT recipients with relapse occurring after HIDT (N=48), MUDT (N=87) and MRDT (N=102) were included in this analysis. Median age was 49 years (19-77 years) and the median time to relapse was 156 days (12-2465) after HCT. HIDT recipients had similar median time to relapse (5.8 vs 4.8 vs 5.5 months, P=0.638) compared with MUDT and MRDT, respectively. One-year PRS was worse among HIDT recipients compared with MRDT and MUDT (17% vs 46% vs 40%, P<0.05). In a multivariate analysis, time to relapse (<3 vs >3 months post transplant), no use of donor lymphocyte infusion (DLI) following relapse, higher Dana Farber disease risk index and HCT comorbidity index scores at the time of transplant and delayed platelet engraftment post transplant were all predictive of worse PRS. This analysis shows that 1-year PRS is inferior among HIDT when compared with MRDT or MUDT. Lower use of DLI after HIDT may have contributed to this inferior survival.

Preferential depletion of host over donor T cells through in vivo decay of active rabbit-anti-thymocyte globulin levels during reduced intensity conditioning.

Inadequate T-cell chimerism following reduced-intensity conditioning transplantation may contribute to graft rejection and disease relapse. Anti-thymocyte globulin (ATG) enhances early donor T-cell chimerism, but may also deplete donor T cells, increasing risks of infection and relapse. We prospectively tested administration of rabbit ATG (rATG) ⩾14 days before the infusion of the graft, followed by in vivo decay of active rATG levels, to selectively deplete host T cells. Twenty-three patients received rATG total dose 4.5 mg/kg on days -16 and -15, fludarabine 30 mg/m(2) per day on day -7 through -3, IV busulfan 130 mg/m(2) per day on days -4 and -3 and cyclophosphamide 1500 mg/m(2) on day -2. rATG levels were therapeutic in all patients on day -14, but were sub-therapeutic (<1 µg/mL) by day 0 in 82% of patients. Median donor T-cell chimerisms on days 30 and 180 were 100% (75-100%) and 100% (90-100%), respectively. Non-relapse mortality and relapse/progression at 48 months were 17 and 30%. Cumulative incidences of acute GvHD grades II-IV and III-IV were 39 and 9%. Median follow-up is 64 months (46-79 months). Survival and disease-free survival at 48 months were 70 and 52%. These data suggest that selective depletion of host T cells using this regimen is a feasible and effective strategy.

Preemptive DLI without withdrawal of immunosuppression to promote complete donor T-cell chimerism results in favorable outcomes for high-risk older recipients of alemtuzumab-containing reduced-intensity unrelated donor allogeneic transplant: a prospective phase II trial.

Although pretransplant alemtuzumab can reduce GVHD following allogeneic transplantation, it may also increase the risk of mixed donor T-cell chimerism and infections. We hypothesized that the early use of DLI without withdrawal of immunosuppressive drugs in patients with mixed T-cell chimerism would lower the risk of relapse without significantly increasing the risk of GVHD post DLI. Thirty-six patients (median age 59 years) were treated in this phase II trial using reduced-intensity conditioning including s.c. alemtuzumab (total dose 43 mg) and a PBSC graft from a matched unrelated donor (UD). DLI without withdrawal of immunosuppressive drugs was administered to all 25 patients with <50% donor T-cell chimerism on day +60. The cumulative risks of acute and chronic GVHD were 42% and 59%, respectively. Estimated probabilities of non-relapse mortality (NRM) at day 100 and 1 year were 3% and 14%, respectively. With a median follow up 2.4 years, estimated survivals at day 100, 1 and 2 years were 97%, 71% and 57%, respectively. In multivariate analysis, the occurrence of acute GVHD was associated with an increased risk of mortality, whereas the occurrence of chronic GVHD had a protective effect, associated with decreased relapse and improved disease-free survival. Low-dose alemtuzumab and preemptive DLI provides favorable transplant outcomes including low NRM in an older patient population with high-risk malignancies undergoing UD transplantation.

Feminisation of UK General Practice: a challenge for the Defence Medical Services?

BACKGROUND: The Defence Medical Services (DMS) primarily recruits its trained General Practitioners (GPs) from the NHS and since 1970, the number of men entering medicine has doubled whereas the number of women has increased 10-fold; female GPs will outnumber their male counterparts by 2017. This study performs a quantitative assessment of the potential impact of feminisation of UK General Practice upon the DMS recruitment and workforce planning. METHODS: General Medial Council General Practice Certificate of Completion of Training (GMC GP CCT) data were analysed to identify any change in the percentage of male and female GP Specialty Training Registrars successfully completing GP vocational training between 2007 and 2012, thus becoming potentially recruitable into the DMS as independent GPs. RESULTS: A 3% increase was seen in the number of women achieving GMC GP CCT between 2007 and 2012 (p=0.015). The percentage of DMS GP Specialty Training Registrars (GPStRs) gaining their GMC GP CCT in 2012 who were women (25%) was about half that seen nationally (59%). A lack of 2007 by-sex GMC GP CCT data for DMS GPStRs prevented a comparison with 2012. CONCLUSIONS: The national increase of only 3% infers feminisation of UK General Practice is not an immediate challenge for the DMS. Nevertheless, as feminisation of the UK GP workforce is expected to continue, the future cohort from whom the DMS will recruit its GPs is likely to contain increasing numbers of women. With the return to contingency, the DMS may wish to consider the implications of increasing numbers of female GPs upon service delivery in the UK and overseas, and explore more flexible medical employment models.

Outpatient myeloablative allo-SCT: a comprehensive approach yields decreased hospital utilization and low TRM.

Historically, myeloablative allogeneic hematopoietic SCT (HSCT) has required prolonged in-patient hospitalization due to the effects of mucosal toxicity and prolonged cytopenias. We explored the safety and feasibility of outpatient management of these patients. A total of 100 consecutive patients underwent a matched-related donor myeloablative allogeneic HSCT for a hematologic malignancy at a single institution. Patients were hospitalized briefly for stem-cell infusion and thereafter only for complications more safely managed in the in-patient setting. The median hospital length of stay from the start of the preparative regimen to day +30 and day +100 post-transplant was 12 and 15 days, respectively. Planned hospital discharge occurred in 79 patients after stem cell infusion. Patients were readmitted to hospital at median of day +7 post transplant, with neutropenic fever being the primary cause for readmission. In total, 18 patients required no in-patient care in the first 100 days. Non-relapse mortality at day 100 and 6 months was 10 and 15%, respectively, for all patients, and 0 and 5%, respectively, for standard risk patients. In summary, outpatient myeloablative allogeneic HSCT with expectant in-patient management can be accomplished safely with low treatment-related morbidity and mortality. Clinical outcomes seem comparable to those reported for traditional in-patient management.

Home administration of high-dose oral busulfan in patients undergoing hematopoietic stem cell transplantation.

We report our experience with oral busulfan (BU) in 159 consecutive patients to evaluate the safety of home administration. Patients received a myeloablative BU-containing regimen, including oral anticonvulsant and antiemetic prophylaxis, followed by hematopoietic stem cell transplantation. Comprehensive verbal and written education was provided. Pharmacokinetic monitoring was performed and dose adjustments were made to target an area under the plasma concentration-time curve (AUC) of 900-1500 micromol.min/l. Safety was assessed by evaluating therapy-related toxicities, including seizures, venoocclusive disease (VOD) and patient tolerability. The utilization of pharmacokinetic monitoring was reviewed as a secondary end point. Of the 143 patients evaluated for BU-related seizures and VOD, only two (1.4%) experienced a generalized seizure and four patients (3%) were diagnosed with VOD. VOD resolved in three patients and was a contributing cause of death in one patient. Additional BU dosing owing to nausea and/or vomiting occurred in 28 patients (18%) and five patients (3%) were hospitalized. The median measured AUC was 1405 micromol.min/l, 68% of patients required a dose adjustment, and the median total administered BU dose was 13.6 mg/kg. In conclusion, high-dose oral BU can be safely administered on an outpatient basis.

Heterochromatic trans-inactivation of Drosophila white transgenes.

Position effect variegation of most Drosophila melanogaster genes, including the white eye pigment gene is recessive. We find that this is not always the case for white transgenes. Three examples are described in which a lesion causing variegation is capable of silencing the white transgene on the paired homologue (trans-inactivation). These examples include two different transgene constructs inserted at three distinct genomic locations. The lesions that cause variegation of white minimally disrupt the linear order of genes on the chromosomes, permitting close homologous pairing. At one of these sites, trans-inactivation has also been extended to include a vital gene in the vicinity of the white transgene insertion. These findings suggest that many Drosophila genes, in many positions in the genome, can sense the heterochromatic state of a paired homologue.

A spiritual well-being model: use with older women who experience depression.

Although evidence exists to suggest an integral influence of one's spirit on one's mental health, few nurse theoreticians have attempted to delineate and include the concept of spirituality in their nursing models. In making practice decisions related to spiritual matters, mental health nurses require knowledge about the interface between spirituality and mental health. Many symptoms of depression, the most common mental health problem of older adults, parallel indications of spiritual distress. The author presents a spiritual well-being model that provides a framework to discuss the antecedents, symptoms, spiritual needs, and holistic treatment of depression as it is experienced by older women.

vnd, a gene required for early neurogenesis of Drosophila, encodes a homeodomain protein.

The development of the central nervous system in Drosophila is initiated by the segregation of neuroblasts, the neural progenitors, from the embryonic neuroectoderm. This process is guided by at least two classes of genes: the achaete-scute complex (AS-C) proneural genes and the neurogenic genes. It has been known for some time that loss-of-function mutations in the AS-C result in neural hypoplasia and the first observed defect is failure of segregation of a fraction of neuroblasts. Loss-of-function mutations at the ventral nervous system defective (vnd) locus are known to lead to similar phenotypic defects in early neurogenesis. More recently, the vnd locus has been implicated in the regulation of the proneural AS-C genes and the neurogenic genes of the Enhancer of split complex. In this paper we report the identification of a transcript associated with the vnd locus, the transcript distribution in embryogenesis, which is compatible with the nervous system mutant phenotypes described for this gene, and that the protein product is a member of the NK-2 homeodomain family. We discuss these findings within the framework of early Drosophila neurogenesis and the known phenotypes associated with the vnd locus.

Conservation of brown gene trans-inactivation in Drosophila.

The mechanism underlying trans-inactivation associated with dominant position effect variegation (PEV) of the Drosophila melanogaster brown gene has been addressed by a comparison with its D. virilis homologue. This comparison revealed: 86% identity between conceptual translation products of the brown gene from these two species, functional homology, as the D. virilis gene rescues a D. melanogaster null brown mutation, and conservation of the sequences required for trans-inactivation, as the D. virilis gene in D. melanogaster is subject to dominant PEV. An extended region of sequence similarity upstream of the open reading frame is observed. As the D. virilis homologue is functionally interchangeable with the D. melanogaster gene, these genes must share regulatory sequences as well as protein coding homology. These results support a model in which trans-inactivation is mediated by a heterochromatin-sensitive transcription factor.

Closed carbon dioxide filtration revisited.

There are compelling reasons why the closed carbon dioxide filtration method for inhalation anaesthesia deserves serious reconsideration. Use of the closed absorption system today can provide all the benefits recognised by those who introduced it seventy to eighty years ago. A most important benefit is the increased opportunity of learning afforded the user, which leads either neophyte or senior clinician to improvement of both concept and clinical skills. The current resurgence of interest is fully appropriate for all physicians who aspire to be true specialists in the care of patients during clinical anaesthesia.

Closed system with agent-specific vaporizers and nitrous oxide.

Through judicious use of nitrous oxide the closed system can be quite effectively used with currently available equipment including both agent-specific direct-reading percentage vaporizers and suitable devices for the measurement of end-tidal concentrations of oxygen, carbon dioxide and anaesthetic agents. It is only necessary to think in terms of required volumes of fresh gases and vapours added to the system as well as the appropriate concentrations of oxygen and anaesthetic in the respired mixture. When used as described the inspired concentration of nitrous oxide in the closed system should never exceed 50% (usually about 40%). Therefore nitrous oxide will not pose the threat of hypoxaemia unless misused. Experience in teaching this method during the previous decade supports a belief that learning the use of a truly closed circle absorption anaesthesia system is fundamentally important to the development of clinical skills and also facilitates understanding of basic concepts related to respiratory physiology and the uptake and distribution of inhalation anaesthetics. It follows that students and residents should be introduced to this method in the early weeks of their learning experience.

Salvage therapy in epithelial ovarian cancer.

Table 1 summarizes studies in which clinical or pathologic response rates can be determined. The majority of patients in these studies had macroscopic drug-resistant tumors, and most had received cisplatin-based chemotherapy. It is noteworthy that the response rate in this group of patients is considerably higher than the 30% to 36% seen with the most active salvage therapies, such as taxol (paclitaxel). Like most trials of salvage chemotherapy for refractory ovarian carcinoma, many responses were short-lived. Toxicity in these studies is comparable to that seen in trials of ASCT in other solid tumors. The promising results observed in these small studies of ASCT in ovarian carcinoma warrant further investigation focused on defining which groups of patients are likely to benefit from this approach. Based on evidence from the lymphohematopoietic malignancies, it would seem reasonable to use ASCT in patients early in the course of their disease before extensive pretreatment and preferably at a time of minimal tumor burden. Some groups have been exploring ASCT as consolidation therapy after surgery and limited debulking chemotherapy. Based on kinetic models of tumor growth, other investigators have suggested that multiple courses of high-dose chemotherapy with ASCT after debulking surgery may result in more cures than a single ASCT after conventional chemotherapy. The feasibility of performing sequential ASCT has been well documented. So far the best drug regimens, the number of cycles that should be used, and the patients who should be candidates for high-dose chemotherapy and ASCT remain undefined. Presently, there is no role for this therapeutic modality outside of well-designed clinical trials.

Prevention and management of graft-versus-host disease. Practical recommendations.

Graft-versus-host disease (GVHD) is the leading cause of failure of allogeneic bone marrow transplantation. The disease typically involves the skin, liver and gastrointestinal tract, with death frequently resulting from infectious complications. Cyclosporin-based drug combinations are the mainstay of GVHD prophylaxis. The major toxicity of cyclosporin is renal dysfunction, and optimal strategies of therapeutic drug monitoring to minimise toxicity and maximise clinical efficacy have yet to be devised. Initial treatment of established GVHD usually includes high dose corticosteroids. Patients failing to respond to first line therapy have a poor prognosis. Investigational approaches to decreasing the mortality associated with GVHD include using monoclonal antibodies directed at specific T cell subsets, and T cell depletion of bone marrow grafts.