In-situ comparison of high-order detonations and low-order deflagration methodologies for underwater unexploded ordnance (UXO) disposal.

The unexploded ordnance (UXO) on the seabed off Northwest Europe poses a hazard to offshore developments such as windfarms. The traditional removal method is through high-order detonation of a donor explosive charge placed adjacent to the UXO, which poses a risk of injury or death to marine mammals and other fauna from the high sound levels produced and is destructive to the seabed. This paper describes a sea-trial in the Danish Great Belt to compare the sound produced by high-order detonations with that produced by deflagration, a low-order disposal method that offers reduced environmental impact from noise. The results demonstrate a substantial reduction over high-order detonation, with the peak sound pressure level and sound exposure level being around 20 dB lower for the deflagration. The damage to the seabed was also considerably reduced for deflagration, although there was some evidence for residues of explosives related chemicals in sediments.

On the Importance of Consistent Insonation Conditions During Hydrophone Calibration and Use.

Hydrophones are generally calibrated in acoustic fields with temporally localized (short pulse) or long duration (tone burst) signals. Free-field conditions are achieved by time gating any reflections from the hydrophone body, mounting structures, and surrounding water tank boundaries arriving at the active sensing element. Consequently, the sensitivity response of the hydrophone is a result of direct waves incident on its active element, free from any contaminating effects of reflections. However, when using tone bursts below 400 kHz to calibrate hydrophones, it may not be possible to isolate the direct wave from reflection artifacts. This means that the sensitivity responses derived at these frequencies using short pulse and tone burst signals might not be comparable as they can be characteristic of the acoustic field interaction with either/both the hydrophone active element alone or the hydrophone active element and body. Therefore, there is a need to consider an appropriate calibration method for a given hydrophone type, depending on whether the eventual application employs short pulse or tone burst acoustic fields. This article presents the findings from a short study comprising four needle-type hydrophones of active element diameters in the range of 1-4 mm. These hydrophones were calibrated from 30 kHz to 1.6 MHz using established calibration methodologies within the underwater acoustics (UWA) and ultrasound (US) areas employed at the National Physical Laboratory (NPL), Teddington, U.K. In UWA tone, burst acoustic fields are used, while in US, it is short pulses. The 2- and 4-mm-diameter needle hydrophones showed the largest variation at the overlapping frequencies, in which the maximum disagreement of UWA calibration was 30% relative to US calibration. For the 4-mm hydrophone, UWA calibration exhibited resonant sensitivity structure between 100 and 450 kHz, but which was absent in US calibration. This observed behavior was further investigated theoretically by using a validated acoustic wave solver to confirm the resonant sensitivity structure seen in the case of UWA calibration. The work contained within illustrates the need to ensure that the method of calibration is carefully considered in the context of the duration of the acoustic signals for which the hydrophone is intended.

Acoustic characterisation of unexploded ordnance disposal in the North Sea using high order detonations.

Results are presented of acoustic measurements made during the disposal of 54 items of unexploded ordnance (UXO) in the North Sea during the pre-construction phase of two offshore windfarms. The disposals were conducted using high-order controlled detonation of donor charges placed on the seabed adjacent to the UXOs. The total charge masses ranged from 2.5 kg to 295 kg TNT equivalent, and acoustic measurements were made at ranges of 1.5 km to 58 km from the UXO. High-order detonations can present a risk of injury or death to marine mammals and other fauna from the high sound levels produced, and these results represent the largest data set of acoustic measurements ever assembled for publication. Acoustic measurements were also made on small scare charges, used as mitigation. The sound pressure pulses are presented with their spectra, and the levels of peak sound pressure and sound exposure are presented as a function of range from the source. Measured levels are compared to data from a shallow-water propagation model, and to widely-adopted exposure level thresholds used for marine mammals, illustrating the potential for injury at distances of several kilometres.

ASTCT, CIBMTR, and EBMT clinical practice recommendations for transplant and cellular therapies in mantle cell lymphoma.

Autologous (auto-) or allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities for mantle cell lymphoma (MCL). Recently, chimeric antigen receptor (CAR) T-cell therapy received approval for MCL; however, its exact place and sequence in relation to HCT is unclear. The ASTCT, CIBMTR, and the EBMT, jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-, allo-HCT, and CAR T-cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated; in the first-line setting auto-HCT consolidation represents standard-of-care in eligible patients, whereas there is no clear role of allo-HCT or CAR T-cell therapy, outside of a clinical trial. In the R/R setting, the preferential option is CAR T-cell therapy especially in MCL failing or intolerant to at least one Bruton's tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T-cell therapy has failed or is not feasible. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL.

American Society of Transplantation and Cellular Therapy, Center of International Blood and Marrow Transplant Research, and European Society for Blood and Marrow Transplantation Clinical Practice Recommendations for Transplantation and Cellular Therapies in Mantle Cell Lymphoma.

Autologous (auto-) and allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities in contemporary treatment algorithms for mantle cell lymphoma (MCL). Chimeric antigen receptor (CAR) T cell therapy recently received approval for MCL; however, its exact place and sequence in relation to HCT remain unclear. The American Society of Transplantation and Cellular Therapy, Center of International Blood and Marrow Transplant Research, and the European Society for Blood and Marrow Transplantation jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-HCT, allo-HCT, and CAR T cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated, with a few key statements as follows: in the first line setting, auto-HCT consolidation represents standard of care in eligible patients, whereas there is no clear role of allo-HCT or CAR T cell therapy outside of clinical trials. In the R/R setting, the preferential option is CAR T cell therapy, especially in patients with MCL failing or intolerant to at least one Bruton's tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T cell therapy fails or is infeasible. Several recommendations were based on expert opinion, where the panel developed consensus statements for important real-world clinical scenarios to guide clinical practice. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL.

Underwater acoustic characterisation of unexploded ordnance disposal using deflagration.

The seabed off North West Europe contains much unexploded ordnance (UXO), posing a hazard to offshore developments such as windfarms. The typical removal method is through high-order detonation of a donor charge placed adjacent to the UXO. This method poses a risk of injury or death to marine mammals and other fauna from the high sound levels produced. This paper describes a controlled field experiment to compare the sound produced by high-order detonations with a low-order disposal method called deflagration, which uses a shaped charge of modest size, is less energetic, and offers reduced environmental impact from lower acoustic output. The results demonstrate a substantial reduction over high order detonation, with the peak sound pressure level and sound exposure level being more than 20 dB lower for the deflagration, and with the acoustic output depending only on the size of the shaped charge (rather than the size of the UXO).

A Radiation Force Balance Target Material for Applications below 0.5 MHz.

Acoustic output power is an important safety-related parameter whose standardised measurement method involves use of a radiation force balance in conjunction with a special target that is typically designed to be totally absorbing to ultrasound. International Standard International Electrotechnical Commission (IEC) 61161 specifies important performance criteria for such an absorber, such as transmission loss and reflection loss. Currently, there is a lack of acoustic absorbers meeting these requirements at low frequencies (<0.5 MHz). This is unsatisfactory given emerging clinical applications, particularly therapeutic. Described here is an acoustic absorber appropriate for application below 0.5 MHz. Through use of two National Physical Laboratory measurement facilities, the absorber transmission loss and reflection loss have been derived over the frequency range 50-500 kHz. Results are presented and compared with performance requirements specified in IEC 61161, revealing the efficacy of the new material as an absorbing radiation force balance target down to a frequency of approximately 120 kHz.

Maintenance Therapies for Hodgkin and Non-Hodgkin Lymphomas After Autologous Transplantation: A Consensus Project of ASBMT, CIBMTR, and the Lymphoma Working Party of EBMT.

IMPORTANCE: Maintenance therapies are often considered as a therapeutic strategy in patients with lymphoma following autologous hematopoietic cell transplantation (auto-HCT) to mitigate the risk of disease relapse. With an evolving therapeutic landscape, where novel drugs are moving earlier in therapy lines, evidence relevant to contemporary practice is increasingly limited. The American Society for Blood and Marrow Transplantation (ASBMT), Center for International Blood and Marrow Transplant Research (CIBMTR), and European Society for Blood and Marrow Transplantation (EBMT) jointly convened an expert panel with diverse expertise and geographical representation to formulate consensus recommendations regarding the use of maintenance and/or consolidation therapies after auto-HCT in patients with lymphoma. OBSERVATIONS: The RAND-modified Delphi method was used to generate consensus statements where at least 75% vote in favor of a recommendation was considered as consensus. The process included 3 online surveys moderated by an independent methodological expert to ensure anonymity and an in-person meeting. The panel recommended restricting the histologic categories covered in this project to Hodgkin lymphoma (HL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma. On completion of the voting process, the panel generated 22 consensus statements regarding post auto-HCT maintenance and/or consolidation therapies. The grade A recommendations included endorsement of: (1) brentuximab vedotin (BV) maintenance and/or consolidation in BV-naïve high-risk HL, (2) rituximab maintenance in MCL undergoing auto-HCT after first-line therapy, (3) rituximab maintenance in rituximab-naïve FL, and (4) No post auto-HCT maintenance was recommended in DLBCL. The panel also developed consensus statements for important real-world clinical scenarios, where randomized data are lacking to guide clinical practice. CONCLUSIONS AND RELEVANCE: In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a rigorous framework for developing consensus recommendations for post auto-HCT maintenance and/or consolidation therapies in lymphoma.

The role of stem cell transplantation in the management of relapsed follicular lymphoma in the era of targeted therapies.

Patients with relapsed follicular lymphoma (FL) following first-line therapy have an increasing number of management strategies ranging from observation through to stem cell transplantation. There has been an exciting expansion in novel agents to treat FL, but at present there is not a universally accepted standard of care in the relapse setting. Decision-making can be difficult for the clinician as there is a paucity of data to compare the various relapse therapies available. This review will discuss conventional therapy for relapsed FL, consider the use of novel agents and explore the role and timing of autologous and allogeneic stem cell transplantation.

Long-term outcome analysis of reduced-intensity allogeneic stem cell transplantation in patients with mantle cell lymphoma: a retrospective study from the EBMT Lymphoma Working Party.

Reduced-intensity allogeneic stem cell transplantation (RIST) is usually reserved for patients with mantle cell lymphoma who relapse after an autoSCT. However, the long-term efficacy of RIST and its curative potential have not been clearly demonstrated. We studied the long-term outcome of patients receiving a RIST for MCL as reported to the EBMT. A total of 324 patients, median age 57 years (range 31-70), underwent a RIST between 2000 and 2008; 43% of the patients had received >3 lines of prior therapy, including an autoSCT in 46%. Non-relapse mortality (NRM) was 10% at 100 days and 24% at 1 year and was lower for patients receiving anti-thymocyte globulin (ATG)/ALG (RR 0.59, p = 0.046). After a median follow-up of 72 months (range 3-159), 118 patients relapsed at a median of 8 months post RIST (range 1-117). The cumulative incidence of relapse was 25% and 40% at 1 and 5 years, respectively, and was associated with chemorefractory disease (HR 0.49, p = 0.01) and the use of CAMPATH (HR 2.59, p = 0.0002). The 4-year progression-free survival rate and overall survival rate was 31 and 40%, respectively. RIST results in long-term disease-free survival in about 30% of the patients, including those patients relapsing after a prior autoSCT.

Measurement and characterisation of radiated underwater sound from a 3.6 MW monopile wind turbine.

This paper describes underwater sound pressure measurements obtained in close proximity (∼50 m) to two individual wind turbines, over a 21-day period, capturing the full range of turbine operating conditions. The sound radiated into the water was characterised by a number of tonal components, which are thought to primarily originate from the gearbox for the bandwidth measured. The main signal associated with the turbine operation had a mean-square sound pressure spectral density level which peaked at 126 dB re 1 µPa2 Hz-1 at 162 Hz. Other tonal components were also present, notably at frequencies between about 20 and 330 Hz, albeit at lower amplitudes. The measured sound characteristics, both in terms of frequency and amplitude, were shown to vary with wind speed. The sound pressure level increased with wind speed up to an average value of 128 dB re 1 µPa at a wind speed of about 10 ms-1, and then showed a general decrease. Overall, differences in the mean-square sound pressure spectral density level of over 20 dB were observed across the operational envelope of the turbine.

Male-biased sex ratio does not promote increased sperm competitiveness in the seed beetle, Callosobruchus maculatus.

Sperm competition risk and intensity can select for adaptations that increase male fertilisation success. Evolutionary responses are examined typically by generating increased strength of sexual selection via direct manipulation of female mating rates (by enforcing monandry or polyandry) or by alteration of adult sex ratios. Despite being a model species for sexual selection research, the effect of sexual selection intensity via adult sex-ratio manipulation on male investment strategies has not been investigated in the seed beetle, Callosobruchus maculatus. We imposed 32 generations of experimental evolution on 10 populations of beetles by manipulating adult sex ratio. Contrary to predictions, males evolving in male-biased populations did not increase their testes and accessory gland size. This absence of divergence in ejaculate investment was also reflected in the fact that males from male-biased populations were not more successful in either preventing females from remating, or in competing directly for fertilisations. These populations already demonstrate divergence in mating behaviour and immunity, suggesting sufficient generations have passed to allow divergence in physiological and behavioural traits. We propose several explanations for the absence of divergence in sperm competitiveness among our populations and the pitfalls of using sex ratio manipulation to assess evolutionary responses to sexual selection intensity.

Measurement of Underwater Operational Noise Emitted by Wave and Tidal Stream Energy Devices.

The increasing international growth in the development of marine and freshwater wave and tidal energy harvesting systems has been followed by a growing requirement to understand any associated underwater impact. Radiated noise generated during operation is dependent on the device's physical properties, the sound-propagation environment, and the device's operational state. Physical properties may include size, distribution in the water column, and mechanics/hydrodynamics. The sound-propagation environment may be influenced by water depth, bathymetry, sediment type, and water column acoustic properties, and operational state may be influenced by tidal cycle and wave height among others This paper discusses some of the challenges for measurement of noise characteristics from these devices as well as a case study of the measurement of radiated noise from a full-scale wave energy converter.

Sex-biased mortality associated with inbreeding in Drosophila melanogaster.

BACKGROUND: One proposed consequence of inbreeding is a skewed sex ratio arising from sex specific mortality in the homogametic sex caused by inbreeding on the sex chromosome. However, recent work suggests that random distortions in sex ratio due to autosomal inbreeding may be of greater importance. In this study, we investigate the effect of biologically realistic levels of inbreeding on sex ratio and sex specific mortality in Drosophila melanogaster. We use two pedigree crossing designs to either maximise or minimise inbreeding on the X-chromosome whilst producing identical autosomal inbreeding. RESULTS: We found increased female mortality and male biased sex ratios associated with inbreeding in our high, but not low, X-inbreeding pedigree. While our results are more consistent with being driven by inbreeding on the X-chromosome than on the autosomes, the marked difference between treatments does not fit closely the expectations of either model. CONCLUSIONS: Our results are only partly consistent with the hypothesis that inbreeding on the X-chromosome can cause greater fitness reductions in the homogametic sex. Whilst the results of our study are not conclusive, they suggest that directional distortions in sex ratio due to inbreeding can occur, and highlight the need for further investigation on this topic.

The granulocytes in neutropenia 1 (GIN 1) study: a safety study of granulocytes collected from whole blood and stored in additive solution and plasma.

OBJECTIVE/AIM: To evaluate the safety of transfusing pooled, whole blood-derived granulocytes in additive solution and plasma (GASP) in 30 recipients. BACKGROUND: Demand for granulocytes in England has increased five-fold. With the advantages of reduced red cell, plasma and overall volume, GASP maintains function in vitro. METHODS AND MATERIALS: Observations were recorded prior to and post transfusion. Increments were recorded at 1 h and the following morning. Leucocyte antibody screening was undertaken prior to and at 1-6 months following transfusion. RESULTS: Thirty patients aged between 8 months and 68 years received 221 GASP in 148 transfusion episodes. GASP contained an average of 1.0 × 10(10) granulocytes in 207 mL. Adults usually received two packs and children 10-20 mL kg(-1). Children and adults received a median [interquartile range (IQR)] dose of 12.5 (9.1-25.3) and 19.7 (12.0-25.8) × 10(9) granulocytes per transfusion, respectively. There was one episode of transfusion-associated circulatory overload (TACO) in a patient with chronic cardiac failure following 600 mL of unpooled granulocytes, other fluids and one GASP. New leucocyte alloimmunisation occurred in 3/30 recipients 10%. No other significant reactions were reported. Median peripheral blood neutrophil increments at 1 h post transfusion were 0.06 (IQR, 0.01-0.17) in children and (0.03) (IQR, 0-0.16) in adults. CONCLUSION: GASP has a similar safety profile to other sources of granulocytes for patients with refractory infection or in need of secondary prophylactic transfusion. Further studies are required to clarify the role of GASP in the treatment of neutropenic patients.

Assortative mating for relatedness in a large naturally occurring population of Drosophila melanogaster.

New theoretical work on kin selection and inclusive fitness benefits predicts that individuals will sometimes choose close or intermediate relatives as mates to maximize their fitness. However, empirical examples supporting such predictions are rare. In this study, we look for such evidence in a natural population of Drosophila melanogaster. We compared mating and nonmating individuals to test whether mating was nonrandom with respect to relatedness. Consistent with optimal inbreeding, males were more closely related to their mate than to randomly sampled females. However, all individuals collected mating showed higher relatedness and males were not significantly more related to their mate than to other mating females. We also found a negative relationship between relatedness and fecundity. Our results are consistent with the hypothesis that inclusive fitness benefits may drive inbreeding tolerance despite direct costs to fitness; however, an experimental approach is needed to investigate the link between mate preference and relatedness.