"‘Inert’ Ingredients Are Understudied, Potentially Dangerous to Bees and Deserve More Research Attention

Agrochemical formulations are composed of two broad groups of chemicals: active ingredients, which confer pest control action, and ‘inert’ ingredients, which facilitate the action of the active ingredient. Most research into the effects of agrochemicals focusses on the effects of active ingredients. This reflects the assumption that ‘inert’ ingredients are non-toxic. A review of relevant research shows that for bees, this assumption is without empirical foundation. After conducting a systematic literature search, we found just 19 studies that tested the effects of ‘inert’ ingredients on bee health. In these studies, ‘inert’ ingredients were found to cause mortality in bees through multiple exposure routes, act synergistically with other stressors and cause colony level effects. This lack of research is compounded by a lack of diversity in study organism used. We argue that ‘inert’ ingredients have distinct, and poorly understood, ecological persistency profiles and toxicities, making research into their individual effects necessary. We highlight the lack of mitigation in place to protect bees from ‘inert’ ingredients and argue that research efforts should be redistributed to address the knowledge gap identified here. If so-called ‘inert’ ingredients are, in fact, detrimental to bee health, their potential role in widespread bee declines needs urgent assessment

Development and automation of a test of impulse control in zebrafish.

Deficits in impulse control (difficulties in inhibition of a pre-potent response) are fundamental to a number of psychiatric disorders, but the molecular and cellular basis is poorly understood. Zebrafish offer a very useful model for exploring these mechanisms, but there is currently a lack of validated procedures for measuring impulsivity in fish. In mammals, impulsivity can be measured by examining rates of anticipatory responding in the 5-choice serial reaction time task (5-CSRTT), a continuous performance task where the subject is reinforced upon accurate detection of a briefly presented light in one of five distinct spatial locations. This paper describes the development of a fully-integrated automated system for testing impulsivity in adult zebrafish. We outline the development of our image analysis software and its integration with National Instruments drivers and actuators to produce the system. We also describe an initial validation of the system through a one-generation screen of chemically mutagenized zebrafish, where the testing parameters were optimized

Taphonomic Comparisons of Two Laurentian Upper Ordovician Epeiric Sea “Small Shelly Faunas”

The Elgin Member of the Upper Ordovician (Katian) Maquoketa Formation of Iowa contains phosphorite beds consisting of millimeter-scale phosphatic fossils, primarily steinkerns. Similar beds occur in the coeval strata of the classic Cincinnatian Series around the Cincinnati, Ohio area. Initial sampling of the phosphate-rich beds of the Maquoketa allows comparison between the faunal composition and taphonomy of these beds and collections from the more extensively sampled Cincinnatian strata. We isolated these fossils by dissolution of bulk samples in acetic acid and examined the same strata in thin section to study the fossils in context. The Maquoketa diminutive phosphatized fossils have been interpreted as evidence of dwarfed faunas indicative of environmental stress, such as anoxia, which may have also contributed to phosphogenesis. An alternative explanation for the small size is that phosphogenesis was size-selective and that phosphatic particles were concentrated by reworking as less-durable shell material was destroyed. These hypotheses can be tested by examining the fauna for “normal” sized elements. Insoluble residue from sampled phosphate-rich strata in both field areas yields abundant molluscan steinkerns, as well as crinoid columnals, conodonts, scolecodonts, bryozoan zooecia steinkerns and other fossils associated with a normal marine fauna. In Cincinnatian occurrences, the composition of the phosphatic assemblages is variable but is a reflection of the variability of faunal composition seen in these strata rather than an indication of an unusual fauna associated with extreme conditions; most are associated with diverse marine assemblages. Insoluble residues from both areas yield steinkerns that precipitated in small pores within larger skeletons. This phenomenon can be seen in thin section, where phosphate is present within certain parts of the larger preserved skeletons. The maximum size of the steinkerns of the Maquoketa is larger than those of most Cincinnatian occurrences, although size is variable in Cincinnatian occurrences. In Cincinnatian strata the abundance of small phosphatic fossils correlates with evidence for reworking; heavily reworked beds yield the most residue. Examined in thin section, the sampled strata of the Maquoketa appear to be heavily reworked and represent an extreme endmember of this concentration of durable phosphatic material. Detailed examination using an SEM and associated XRF elemental mapping reveals that the phosphatic steinkerns of both localities are very similar in their taphonomy. Both consist of botryoidal growths of carbonate fluorapatite (CFA). The botryoidal growth appears to have nucleated on the walls of the original shell, first forming a lining of variable thickness. Some steinkerns have secondary botryoidal growths on the outside of the steinkern indicating continued precipitation of CFA after destruction of the original shell. This secondary precipitation suggests that reworking played a role not only in concentrating the phosphatic material but also in encouraging continued precipitation of CFA. The size of the available pore space appears to have played a role in encouraging the precipitation of CFA. In thin section the CFA is limited to smaller parts of larger shells, such as the apices of gastropods and did not precipitate on the inside of the larger, more open spaces within the shell. Many of the phosphate-filled spaces are also sediment-filled, suggesting that subdivision of the larger space into smaller pores enhanced the precipitation of CFA. The difference in the maximum size of the steinkern achieved in the different assemblages suggests that geochemical factors affected size limits. The most distinctive aspect of phosphate-rich Ordovician strata of mid-Laurentia is the degree of reworking that concentrated the durable small fossils. Details of taphonomy also suggest that phosphate precipitation was an iterative process enhanced by reworking, and that small pore spaces enhanced this mineralization, thus selectively preserving certain sizes and parts of the larger fauna

Night Matters—Why the Interdisciplinary Field of “Night Studies” Is Needed

The night has historically been neglected in both disciplinary and interdisciplinary research. To some extent, this is not surprising, given the diurnal bias of human researchers and the difficulty of performing work at night. The night is, however, a critical element of biological, chemical, physical, and social systems on Earth. Moreover, research into social issues such as inequality, demographic changes, and the transition to a sustainable economy will be compromised if the night is not considered. Recent years, however, have seen a surge in research into the night. We argue that “night studies” is on the cusp of coming into its own as an interdisciplinary field, and that when it does, the field will consider questions that disciplinary researchers have not yet thought to ask

Time-richness and phosphatic microsteinkern accumulation in the Cincinnatian (Katian) Ordovician, USA: An example of polycyclic phosphogenic condensation

Millimeter-scale phosphatic steinkern preservation is a feature of the taxonomically enigmatic Early Cambrian “small shelly faunas”, but this style of preservation is not unique to the Cambrian; it is ubiquitous, if infrequently reported, from the Phanerozoic record. The polycyclic phosphogenic condensation (PPC) model envisions both the genesis and concentration of phosphatic microsteinkerns as natural outcomes of shell bed genesis through episodic sediment starvation. This model predicts that more reworked and condensed shell bed limestones will contain more phosphatic microsteinkerns, but that even the least reworked limestones may contain some phosphatic particles. We test this model through examination of vertical thin sections densely collected through a 10-meter interval from the classic Cincinnatian (upper Katian, middle Maysvillian North American Stage) upper Fairview Formation, Miamitown Shale, and lower Grant Lake formations at four localities near Cincinnati, Ohio. For each of approximately 50 distinguishable limestone depositional units in each locality, a 2 × 2 cm square was selected for study. Each square was assigned a textural classification (mud content of intergranular space) and a breakage rank (pristine to comminuted). Phosphatic particle distribution was quantified both by visual estimation and by particle counting, with counts ranging from none detected to over 1000 per 4 cm2. Our analyses show a strong positive relationship between phosphate content and both textural maturity and fragmentation. This positive relationship is consistent with the PPC model and confirms that textural maturity can reflect the degree of condensation as well as depth-related environmental energy. This finding suggests that shell bed processes of repeated deposition and reworking make a significant contribution to the generation and accumulation of phosphatic particles. If local-scale sedimentary processes and conditions can control this accumulation, temporal changes in phosphatic sediment deposition rates may be linked to earth changes more complexly than through changing ocean chemistry on a global scale

Total prostatectomy as a treatment for prostatic carcinoma in 25 dogs

Objective: To describe the complications and outcome after total prostatectomy in dogs with histologically confirmed prostatic carcinoma. Study Design: Multi-institutional retrospective case series. Animals: 25 client-owned dogs. Methods: Medical records of dogs undergoing total prostatectomy were reviewed from 2004 to 2016. Data retrieved included signalment, presenting signs, preoperative clinical findings, laboratory data, diagnostic imaging, surgical technique, histologic diagnosis, postoperative complications, occurrence of postoperative metastasis, and survival. Results: Twenty-five dogs underwent total prostatectomy for prostatic carcinoma. Urinary anastomotic techniques included urethrourethral anastomosis in 14 dogs, cystourethral anastomosis in 9 dogs, ureterocolonic anastomosis in 1 dog, and anastomosis between the bladder neck and penile urethra in 1 dog. All dogs survived to discharge. Fifteen dogs were diagnosed with transitional cell carcinoma, 8 dogs with prostatic adenocarcinoma, 1 with prostatic cystadenocarcinoma, and 1 with an undifferentiated carcinoma. Permanent postoperative urinary incontinence was present in 8 of 23 dogs. The median survival time was shorter in dogs with extracapsular tumor extension compared with those with intracapsular tumors. The overall median survival time was 231 days (range, 24-1255), with 1- and 2-year survival rates equal to 32% and 12%, respectively. Conclusion and Clinical Significance: Total prostatectomy, combined with adjunct therapies, prolongs survival and lowers complication rates compared to previous reports of dogs with prostatic carcinoma. It should be noted, however, that case selection likely played a significant role in postoperative outcome

Fifteen-minute consultation: public health for paediatricians-adolescent public health

Paediatricians have a key role to play in ensuring a holistic, integrated approach is taken to meeting adolescent health needs. There is increasing evidence that failure to do so can lead to poor healthcare experience, avoidable ill health and increased need for healthcare services, both in the short term and in adult life. This article aims to guide paediatricians in answering the questions 'How well are the public health and clinical needs of the adolescent population in my area being met? And how can we improve?

Intra-specific variation in sensitivity of <i>Bombus terrestris</i> and <i>Osmia bicornis</i> to three pesticides

There is growing evidence that pesticides may be among the causes of worldwide bee declines, which has resulted in repeated calls for their increased scrutiny in regulatory assessments. One recurring concern is that the current frameworks may be biased towards assessing risks to the honey bee. This paradigm requires extrapolating toxicity information across bee species. Most research effort has therefore focused on quantifying differences in sensitivity across species. However, our understanding of how responses to pesticides may vary within a species is still very poor. Here we take the first steps towards filling this knowledge gap by comparing acute, lethal hazards in sexes and castes of the eusocial bee Bombus terrestris and in sexes of the solitary bee Osmia bicornis after oral and contact exposure to the pesticides sulfoxaflor, Amistar (azoxystrobin) and glyphosate. We show that sensitivity towards pesticides varies significantly both within and across species. Bee weight was a meaningful predictor of pesticide susceptibility. However, weight could not fully explain the observed differences, which suggests the existence of unexplored mechanisms regulating pesticide sensitivity across bee sexes and castes. Our data show that intra-specific responses are an overlooked yet important aspect of the risk assessment of pesticides in bees

The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor

Background Multiple myeloma is a plasma cell tumour with approximately 5500 new cases in the UK each year. Ixazomib is a next generation inhibitor of the 20S proteasome and is thought to be an effective treatment for those who have relapsed from bortezomib. The combination of cyclophosphamide and dexamethasone (CD) is a recognised treatment option for patients with relapsed refractory multiple myeloma (RRMM) who have relapsed after treatment with bortezomib and lenalidomide, whilst also often being combined with newer proteasome inhibitors. The most apparent combination for ixazomib is therefore with CD. Methods MUK eight is a randomised, controlled, open, parallel group, multi-centre phase II trial that will recruit patients with RRMM who have relapsed after treatment with thalidomide, lenalidomide, and a proteasome inhibitor. The primary objective of the trial is to evaluate whether ixazomib in combination with cyclophosphamide and dexamethasone (ICD) has improved clinical activity compared to CD in terms of progression-free survival (PFS). Secondary objectives include comparing toxicity profiles and the activity and cost-effectiveness of both treatments. Since opening, the trial has been amended to allow all participants who experience disease progression (as per the IMWG criteria) on the CD arm to subsequently switch to receive ICD treatment, once progression has been confirmed with two clinical members of the Trial Management Group (TMG). This ‘switch’ phase of the study is exploratory and will assess second progression-free survival measured from randomisation to second disease progression (PFS2) and progression-free survival from the point of switching to second disease progression (PFS Switch) in participants who switch from CD to ICD treatment. Discussion Development of ixazomib offers the opportunity to further investigate the value of proteasome inhibition through oral administration in the treatment of RRMM. Previous studies investigating the safety and efficacy of ICD in patients with RRMM demonstrate a toxicity profile consistent with ixazomib in combination with lenalidomide and dexamethasone, whilst the combination showed possible activity in RRMM patients. Further investigation of the anti-tumour effect of this drug in RRMM patients is therefore warranted, especially since no trials comparing CD with ICD have been completed at present. Trial registration ISRCTN number: ISRCTN58227268. Registered on 26 August 2015