The behavior of Acerocephala hanuuanamusp. nov. found parasitizing Cryphalus brasiliensis under the surface of wood in Ficus microcarpa trees on the island of O‘ahu in Hawai‘i is deduced from observations in naturally occuring branches, and from direct observation using specially designed “phloem sandwich” observation chambers which consist of tree bark peeled through the phloem layer from freshly cut branches and sandwiched between a sheet of aluminum and a sheet of plexiglass. Cryphalus brasiliensis beetles, found living in large numbers in the phloem tissues in F. microcarpa trees, were collected and placed into these chambers. They tunneled into the wood and reproduced, producing an active colony of all life stages. Acerocephala hanuuanamu wasps were then placed into the system and their behavior observed. Typical behavior, aspects of which were recorded in video and still images, was as follows. A female A. hanuuanamu enters the tunnels of the bark beetles. She digs through the debris in the tunnels in a search for larvae and pupae. Cryphalus brasiliensis prepupae construct a hard pupal chamber around themselves before they pupate, and upon encountering a larva in the tunnels or the exterior of a pupal chamber with a pupa inside, she adeptly turns around in the tunnel to sting it, either inserting her ovipositor directly into the larva or by laboriously pushing it through the hard shell of the pupal chamber. When finished stinging, she withdraws her ovipositor slowly and carefully, often extracting tissue from the beetle immature as a sheath around her ovipositor. This structure remains projecting from the larva or pupa, and then the wasp turns around and host feeds through this structure, in the case of a pupa at a substantial distance through the wall of the pupal chamber. Oviposition occurs on larval stages and pupal stages. The egg hatches and the larva develops as an ectoparasitoid on the beetle. When finished feeding, it detaches and pupates in the tunnel. Mating behavior is also described. In addition to C. brasiliensis in F. microcarpa, A. hanuuanamu was also observed attacking Cryphalus mangiferae in mango (Mangifera indica) branches. Acerocephala ihulenasp. nov. was also found on O‘ahu parasitizing Eidophelus pacificus in hau (Hibiscus tiliaceus) branches, and is described. The genus Acerocephala is revised given the perspective resulting from these two new species and aspects of functional morphology observed in the behavioral studies, Acerocephala indicacomb. nov. is transferred to the genus, and a key to the genus is provided.

The twolined spittlebug, Prosapia bicincta (Say), is a major economic pest of forage grass and turfgrass. Prosapia bicincta was first detected in rangelands on Hawai'i Island in 2016 and has since spread to an estimated 72,000 ha in the North and South Kona districts. This study aimed to quantify P. bicincta abundance, plant associations, and impacts on groundcover over time. Monthly surveys of P. bicincta nymphs and adults were conducted from February 2018 to September 2022 along 17 established 100-m transects at 4 ranches located in Kona, Hawai'i Island, spanning an elevation gradient from 519 to 1,874 m above sea level (a.s.l.). Monitoring revealed P. bicincta occurs from 519 to 1,679 m a.s.l., primarily in Kikuyu grass (Cenchrus clandestinus (Hochst. ex Chiov.)) Morrone (Poales: Poaceae) pastures. Peaks in P. bicincta abundance coincided with the wet season, with most activity occurring from April to October and little to no activity between November and March. Mid elevation (1,000-1,300 m) transects had significantly higher mean P. bicincta abundance (126 nymphs/m(2)) relative to low (500-999 m) (64 nymphs/m(2)) and high elevations (>1,300 m) (20 nymphs/m(2)). Sites with the highest abundance of P. bicincta were also associated with the greatest decrease in mean grass cover (30%) and were replaced by forbs, bare ground, and shrubs. Grasses accounted for 72% of the total P. bicincta detections, with the remaining plants comprised of legumes (16%), sedges (6%), and forbs (6%). Twenty new P. bicincta plant associations were found. This information will help improve the effectiveness of management to suppress populations below economic thresholds.

Systemic lupus erythematosus (SLE, lupus) is a debilitating, multisystem autoimmune disease that can affect any organ in the body. The disease is characterized by circulating autoantibodies that accumulate in organs and tissues, which triggers an inflammatory response that can cause permanent damage leading to significant morbidity and mortality. Lyn, a member of the Src family of non-receptor protein tyrosine kinases, is highly implicated in SLE as remarkably both mice lacking Lyn or expressing a gain-of-function mutation in Lyn develop spontaneous lupus-like disease due to altered signaling in B lymphocytes and myeloid cells, suggesting its expression or activation state plays a critical role in maintaining tolerance. The past 30 years of research has begun to elucidate the role of Lyn in a duplicitous signaling network of activating and inhibitory immunoreceptors and related targets, including interactions with the interferon regulatory factor family in the toll-like receptor pathway. Gain-of-function mutations in Lyn have now been identified in human cases and like mouse models, cause severe systemic autoinflammation. Studies of Lyn in SLE patients have presented mixed findings, which may reflect the heterogeneity of disease processes in SLE, with impairment or enhancement in Lyn function affecting subsets of SLE patients that may be a means of stratification. In this review, we present an overview of the phosphorylation and protein-binding targets of Lyn in B lymphocytes and myeloid cells, highlighting the structural domains of the protein that are involved in its function, and provide an update on studies of Lyn in SLE patients.

ObjectivesThis aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement.Study designThis was a modified Delphi process.MethodsWe recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised.ResultsWe had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary.ConclusionsWe developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination.

Introduction Liver disease deaths are rising, but specialist palliative care services for hepatology are limited. Expansion across the NHS is required. Methods We surveyed clinicians, patients and carers to design an ‘ideal’ service. Using standard NHS tariffs, we calculated the cost of this service. In hospitals where specialist palliative care was available for liver disease, patient-level costs and bed utilisation in last year of life (LYOL) were compared between those seen by specialist palliative care before death and those not. Results The ‘ideal’ service was described. Costs were calculated as whole time equivalent for a minimal service, which could be scaled up. From a hospital with an existing service, patients seen by specialist palliative care had associated costs of £14 728 in LYOL, compared with £18 558 for those dying without. Savings more than balanced the costs of introducing the service. Average bed days per patient in LYOL were reduced (19.4 vs 25.7) also intensive care unit bed days (1.1 vs 1.8). Despite this, time from first admission in LYOL to death was similar in both groups (6 months for the specialist palliative care group vs 5 for those not referred). Conclusions We have produced a template business case for an ‘ideal’ advanced liver disease support service, which self-funds and saves many bed days. The model can be easily adapted for local use in other trusts. We describe the methodology for calculating patient-level costs and the required service size. We present a financially compelling argument to expand a service to meet a growing need.

Psychosocial stress increases the risk of a myocardial infarction 2-fold and is associated with a 40% higher risk of death following an acute thrombotic event. With approximately a third of US adults reporting overwhelming stress levels most days, defining the mechanisms by which stress contributes to adverse thrombosis is paramount. Platelets are key contributors to thrombotic cardiovascular events, with platelet hyperreactivity associated with thrombosis and psychosocial stress. In humans and mouse models, psychosocial stress induces a hyperreactive platelet phenotype and increases the risk of thrombosis. To investigate how stress contributes to platelet hyperreactivity, platelets were isolated from 1) mice that experienced chronic variable stress and stress-free controls (n=8/group) and 2) human subjects with self-reported high and no stress levels (n=18/group) and RNA-sequencing performed. By comparison of mutually expressed transcripts, we identified a subset of genes differentially expressed following psychosocial stress in both human and mouse platelets. To assess the contribution of the identified transcripts to platelet functional responses that underlie thrombosis, the association of identified genes with platelet aggregation to epinephrine (0.4 μM) was assessed. Amongst screened candidates, the tetraspanin CD37 was significantly associated with platelet aggregation in a cohort of participants whose platelet aggregation and platelet transcriptome were measured simultaneously (R=0.30, p=0.0002, n=145). Following confirmation of CD37 expression in platelets at the transcriptomic and protein level in humans and mice, we assessed the functional outcome of platelet CD37 deficiency. Cd37-/- platelets spread significantly less relative to wild-type platelets on both poly-D-lysine and fibrinogen (p<0.01 and p<0.005, respectively) and underwent a minimal change in morphology following fibrinogen adhesion. Platelet solidity, a proxy measure inversely proportional to efficient maximal spreading mediated by filopodial-to-lamellipodial transitions, was significantly decreased in wild-type platelets relative to Cd37-/- (p<0.0001), indicative of a spreading dysfunction in CD37 deficient platelets. In whole blood flood cytometry, platelet expression of activated integrin αIIbβ3 (JON/A) and CD63 is significantly attenuated on Cd37-/- platelets relative to wild-type following stimulation with PAR4-AP (p<0.0001, p<0.05, respectively). However, JON/A and CD63 expression is unaltered under resting conditions between Cd37-/- and wild-type platelets. Consistent with a role for CD37 in regulating thrombosis-relevant platelet activation responses, chimeric mice that received Cd37-/- bone marrow experienced a significantly increased time to vessel occlusion (p<0.05) in the carotid artery FeCl3 model, relative to mice reconstituted with wild-type bone marrow. CD37 deficiency does not alter hemostasis, as platelet count, coagulation metrics, prothrombin time, and partial thromboplastin time do not differ in Cd37-/- mice relative to wild-type mice. Consistent with this, bleeding time does not differ between wild-type and Cd37-/- mice following tail tip transection. In humans and mice, platelet CD37 positively associates with platelet aggregation and phenotypic responses that underlie thrombosis. Cd37-deficient platelets exhibit impaired integrin αIIbβ3 signaling, characterized by reduced platelet fibrinogen spreading and decreased agonist-induced αIIbβ3 activation. Notably, CD37 deficiency significantly reduces thrombotic risk without altering hemostasis or bleeding susceptibility. This study provides new insight into a platelet-associated stress-induced mechanism contributing to accelerated thrombotic risk and provides the first direct evidence for CD37 as a regulator of platelet activation responses and thrombosis.

Advanced cirrhosis confers a significant symptom burden and has a 50% 2-year mortality rate in those with decompensated disease. There is increasing demand for supportive and palliative care (SAPC) for these patients, yet no consensus on the best model of delivery. It is necessary to identify the needs of such patients and their carers, and evaluate whether they are being met.A literature search was conducted using key words pertaining to adult patients with liver cirrhosis and their SAPC needs. Study quality was assessed and findings grouped by theme. 51 full texts were selected for inclusion, 8 qualitative studies, 33 quantitative studies, 7 systematic reviews, 2 mixed methods studies and 1 Delphi methods. Key findings were grouped into three main themes: SAPC needs, access to SAPC and models of care.Patients with cirrhosis have significant psychological and physical symptom burden with many unmet needs. These data failed to identify the best service model of care. The impact of specialist palliative care (SPC) referral was limited by small numbers and late referrals. With the majority of studies conducted in the USA, it is unclear how well these findings translate to other healthcare systems. Comparison between hepatology led services and SPC was limited by inconsistent outcome measures and prevented pooling of data sets. These data also had limited evaluation of patient-reported outcome measures. We propose the development of a core outcome set to ensure consistent and meaningful evaluation of the SAPC needs of patients with advanced non-malignant liver cirrhosis.

Aspects of the life history and biology of two Prorops spp. are explored, Prorops mayasp. nov. and Prorops umiehusp. nov. Aspects of their behavior are deduced through dissection of plant material and through the use of “phloem sandwich” style observation chambers. Both were found to be ectoparasitoids of adult Hypothenemus eruditus beetles. They thus show a novel feeding behavior as, along with a Plastanoxus sp., the only bethylids known to parasitize the adult stage of their hosts, and the only known ectoparasitoids of adult scolytids. Searching, stinging, host feeding, and oviposition behaviors are reported and illustrated with photographs and video. Oviposition occurs on the ventral side of the membraneous region between the pro- and mesothorax of the beetle, and larvae feed through this location. The projection on the frons, a defining character of the genus Prorops, is observed to function as a tongue and groove mechanism with which the adult female pushes on the edge of the prothoracic sclerite of the host beetle while maintaining use of its mandibles to chew on the membrane underneath for host feeding and in preparation for oviposition. Defensive action of a Hypothenemus sp. against the wasp's sting by clamping down on the intruding ovipositor between its pro- and mesothorax is also reported, though this behavior was only observed once and thus its generality is uncertain.