Waveguide-integrated silicon T centres.

The performance of modular, networked quantum technologies will be strongly dependent upon the quality of their quantum light-matter interconnects. Solid-state colour centres, and in particular T centres in silicon, offer competitive technological and commercial advantages as the basis for quantum networking technologies and distributed quantum computing. These newly rediscovered silicon defects offer direct telecommunications-band photonic emission, long-lived electron and nuclear spin qubits, and proven native integration into industry-standard, CMOS-compatible, silicon-on-insulator (SOI) photonic chips at scale. Here we demonstrate further levels of integration by characterizing T centre spin ensembles in single-mode waveguides in SOI. In addition to measuring long spin T1 times, we report on the integrated centres' optical properties. We find that the narrow homogeneous linewidth of these waveguide-integrated emitters is already sufficiently low to predict the future success of remote spin-entangling protocols with only modest cavity Purcell enhancements. We show that further improvements may still be possible by measuring nearly lifetime-limited homogeneous linewidths in isotopically pure bulk crystals. In each case the measured linewidths are more than an order of magnitude lower than previously reported and further support the view that high-performance, large-scale distributed quantum technologies based upon T centres in silicon may be attainable in the near term.

A two-qubit logic gate in silicon.

Quantum computation requires qubits that can be coupled in a scalable manner, together with universal and high-fidelity one- and two-qubit logic gates. Many physical realizations of qubits exist, including single photons, trapped ions, superconducting circuits, single defects or atoms in diamond and silicon, and semiconductor quantum dots, with single-qubit fidelities that exceed the stringent thresholds required for fault-tolerant quantum computing. Despite this, high-fidelity two-qubit gates in the solid state that can be manufactured using standard lithographic techniques have so far been limited to superconducting qubits, owing to the difficulties of coupling qubits and dephasing in semiconductor systems. Here we present a two-qubit logic gate, which uses single spins in isotopically enriched silicon and is realized by performing single- and two-qubit operations in a quantum dot system using the exchange interaction, as envisaged in the Loss-DiVincenzo proposal. We realize CNOT gates via controlled-phase operations combined with single-qubit operations. Direct gate-voltage control provides single-qubit addressability, together with a switchable exchange interaction that is used in the two-qubit controlled-phase gate. By independently reading out both qubits, we measure clear anticorrelations in the two-spin probabilities of the CNOT gate.

What is a Quantum Shock Wave?

Shock waves are examples of the far-from-equilibrium behavior of matter; they are ubiquitous in nature, yet the underlying microscopic mechanisms behind their formation are not well understood. Here, we study the dynamics of dispersive quantum shock waves in a one-dimensional Bose gas, and show that the oscillatory train forming from a local density bump expanding into a uniform background is a result of quantum mechanical self-interference. The amplitude of oscillations, i.e., the interference contrast, decreases with the increase of both the temperature of the gas and the interaction strength due to the reduced phase coherence length. Furthermore, we show that vacuum and thermal fluctuations can significantly wash out the interference contrast, seen in the mean-field approaches, due to shot-to-shot fluctuations in the position of interference fringes around the mean.

Systematic reanalysis of genomic data improves quality of variant interpretation.

As genomic sequencing expands, so does our knowledge of the link between genetic variation and disease. Deeper catalogs of variant frequencies improve identification of benign variants, while sequencing affected individuals reveals disease-associated variation. Accumulation of human genetic data thus makes reanalysis a means to maximize the benefits of clinical sequencing. We implemented pipelines to systematically reassess sequencing data from 494 individuals with developmental disability. Reanalysis yielded pathogenic or likely pathogenic (P/LP) variants that were not initially reported in 23 individuals, 6 described here, comprising a 16% increase in P/LP yield. We also downgraded 3 LP and 6 variants of uncertain significance (VUS) due to updated population frequency data. The likelihood of identifying a new P/LP variant increased over time, as ~22% of individuals who did not receive a P/LP variant at their original analysis subsequently did after 3 years. We show here that reanalysis and data sharing increase the diagnostic yield and accuracy of clinical sequencing.

Foraging strategies of a generalist marine predator inhabiting a dynamic environment.

Intraspecific variability is increasingly recognized as an important component of foraging behavior that can have implications for both population and community dynamics. We used an individual-level approach to describe the foraging behavior of an abundant, generalist predator that inhabits a dynamic marine ecosystem, focusing specifically on the different foraging strategies used by individuals in the same demographic group. We collected data on movements and diving behavior of adult female California sea lions (Zalophus californianus) across multiple foraging trips to sea. Sea lions (n = 35) used one of three foraging strategies that primarily differed in their oceanic zone and dive depth: a shallow, epipelagic strategy, a mixed epipelagic/benthic strategy, and a deep-diving strategy. Individuals varied in their degree of fidelity to a given strategy, with 66 % of sea lions using only one strategy on all or most of their foraging trips across the two-month tracking period. All foraging strategies were present in each of the sampling years, but there were inter-annual differences in the population-level importance of each strategy that may reflect changes in prey availability. Deep-diving sea lions traveled shorter distances and spent a greater proportion of time at the rookery than sea lions using the other two strategies, which may have energetic and reproductive implications. These results highlight the importance of an individual-based approach in describing the foraging behavior of female California sea lions and understanding how they respond to the seasonal and annual changes in prey availability that characterize the California Current System.

Bayesian model-averaged benchmark dose analysis via reparameterized quantal-response models.

An important objective in biomedical and environmental risk assessment is estimation of minimum exposure levels that induce a pre-specified adverse response in a target population. The exposure points in such settings are typically referred to as benchmark doses (BMDs). Parametric Bayesian estimation for finding BMDs has grown in popularity, and a large variety of candidate dose-response models is available for applying these methods. Each model can possess potentially different parametric interpretation(s), however. We present reparameterized dose-response models that allow for explicit use of prior information on the target parameter of interest, the BMD. We also enhance our Bayesian estimation technique for BMD analysis by applying Bayesian model averaging to produce point estimates and (lower) credible bounds, overcoming associated questions of model adequacy when multimodel uncertainty is present. An example from carcinogenicity testing illustrates the calculations.

AKAP150-anchored PKA regulation of synaptic transmission and plasticity, neuronal excitability and CRF neuromodulation in the lateral habenula.

Numerous studies of hippocampal synaptic function in learning and memory have established the functional significance of the scaffolding A-kinase anchoring protein 150 (AKAP150) in kinase and phosphatase regulation of synaptic receptor and ion channel trafficking/function and hence synaptic transmission/plasticity, and neuronal excitability. Emerging evidence also suggests that AKAP150 signaling may play a critical role in brain's processing of rewarding/aversive experiences. Here we focused on an unexplored role of AKAP150 in the lateral habenula (LHb), a diencephalic brain region that integrates and relays negative reward signals from forebrain striatal and limbic structures to midbrain monoaminergic centers. LHb aberrant activity (specifically hyperactivity) is also linked to depression. Using whole cell patch clamp recordings in LHb of male wildtype (WT) and ΔPKA knockin mice (with deficiency in AKAP-anchoring of PKA), we found that the genetic disruption of PKA anchoring to AKAP150 significantly reduced AMPA receptor (AMPAR)-mediated glutamatergic transmission and prevented the induction of presynaptic endocannabinoid (eCB)-mediated long-term depression (LTD) in LHb neurons. Moreover, ΔPKA mutation potentiated GABAA receptor (GABAAR)-mediated inhibitory transmission postsynaptically while increasing LHb intrinsic neuronal excitability through suppression of medium afterhyperpolarizations (mAHPs). Given that LHb is a highly stress-responsive brain region, we further tested the effects of corticotropin releasing factor (CRF) stress neuromodulator on synaptic transmission and intrinsic excitability of LHb neurons in WT and ΔPKA mice. As in our earlier study in rat LHb, CRF significantly suppressed GABAergic transmission onto LHb neurons and increased intrinsic excitability by diminishing small-conductance potassium (SK) channel-mediated mAHPs. ΔPKA mutation-induced suppression of mAHPs also blunted the synaptic and neuroexcitatory actions of CRF in mouse LHb. Altogether, our data suggest that AKAP150 complex signaling plays a critical role in regulation of AMPAR and GABAAR synaptic strength, glutamatergic plasticity and CRF neuromodulation possibly through AMPAR and potassium channel trafficking and eCB signaling within the LHb.

Deadly diving? Physiological and behavioural management of decompression stress in diving mammals.

Decompression sickness (DCS; 'the bends') is a disease associated with gas uptake at pressure. The basic pathology and cause are relatively well known to human divers. Breath-hold diving marine mammals were thought to be relatively immune to DCS owing to multiple anatomical, physiological and behavioural adaptations that reduce nitrogen gas (N(2)) loading during dives. However, recent observations have shown that gas bubbles may form and tissue injury may occur in marine mammals under certain circumstances. Gas kinetic models based on measured time-depth profiles further suggest the potential occurrence of high blood and tissue N(2) tensions. We review evidence for gas-bubble incidence in marine mammal tissues and discuss the theory behind gas loading and bubble formation. We suggest that diving mammals vary their physiological responses according to multiple stressors, and that the perspective on marine mammal diving physiology should change from simply minimizing N(2) loading to management of the N(2) load. This suggests several avenues for further study, ranging from the effects of gas bubbles at molecular, cellular and organ function levels, to comparative studies relating the presence/absence of gas bubbles to diving behaviour. Technological advances in imaging and remote instrumentation are likely to advance this field in coming years.

Haemodynamics in women with untreated pre-eclampsia.

This study aimed to compare the haemodynamics in healthy pregnant women with the haemodynamics in women with untreated pre-eclampsia, to determine the cardiovascular reason for hypertension in pre-eclampsia. 40 women with untreated pre-eclampsia, 40 matched healthy pregnant women and 20 non-pregnant women were studied using transthoracic echocardiography. Untreated pre-eclampsia demonstrated (mean (SD), healthy non-pregnant vs healthy pregnant vs untreated pre-eclampsia) increased cardiac output (3400 (752) vs 4109 (595) vs 4789 (1416) ml.min(-1), p=0.002), increased stroke volume (53 (10) vs 53 (8) vs 59 (13) ml, p=0.04), increased fractional shortening (35 (5) vs 35 (7) vs 41 (8) %, p=0.006), increased fractional area change (57 (7) vs 57 (9) vs 65 (9)%, p=0.002) and increased systemic vascular resistance (2116 (457) vs 1613 (315) vs 2016 (625) dyne.s.cm(-5), p=0.001). Mitral E/septal e' was higher (6.0 (1.1) vs 6.7 (1.3) vs 10.4 (2.4), p=0.002) and left atrial size increased (3.2 (0.3) vs 3.8 (0.4) vs 4.0 (0.4) cm, p=0.002). Hypertension in untreated pre-eclampsia is due to increased cardiac output and mild vasoconstriction, with increased inotropy and reduced diastolic function.

Iodinating ability of various leukocytes and their bactericidal activity.

A rapid method that employs monolayers of different phagocytic cells, primarily from guinea pigs and mice, has allowed a kinetic determination of (a) ingestion by these cells of labeled particles, (b) fixation of (131)I and (c) microbicidal activity in the cells after periods as short as 5' of exposure of bacteria to phagocytes. Phagocytes so examined included polymorphonuclear leukocytes (PMN) elicited into the peritoneal cavity, elicited peritoneal mononuclear cells (monocytes) (MN), and peritoneal macrophages (MAC) obtained simply by lavage. Circulating PMN from normal human subjects and from children afflicted with chronic granulomatous disease were also studied. The potential for generation of H(2)O(2) (a key component of the iodinating system) of all the normal cells studied, gauged by their content of cyanide-insensitive NADH oxidase, seemed comparable. Peroxidase levels varied widely, and were highest in PMN and almost undetectable in MAC. Catalase was at negligible levels in all the cell types obtained from mice. The fixation of (131)I by phagocytes ingesting (14)C-labeled dead tubercle bacilli appeared to be primarily a function of the cellular peroxidase content. Thus, mouse macrophages, with virtually no peroxidase, displayed no fixation of iodide. PMN proved far more able to fix (131)I during phagocytosis than did MN. In experiments comparing PMN from normal human subjects and from children with chronic granulomatous disease (CGD), a sex-linked condition characterized by a deficiency of H(2)O(2) production during phagocytosis and low microbicidal activity, the iodination ratio of CGD cells was dramatically less than that of normal PMN (by about two orders of magnitude). Capacity for iodination was correlated with bactericidal activity toward E. coli. At low bacterial loads (ca. 5:1), phagocytes killed efficiently, and little discrepancy in ability among cell types was apparent. Under the stress of higher loads of (14)C-labeled E. coli (ca. 100:1), differences in bactericidal activity were exaggerated, and a substantial disparity between MN and PMN was observed in favor of the latter. The hierarchy for killing efficiencies therefore agreed with that for iodination, with one notable exception: mouse MAC were consistently competent in their killing activity, more so than MN, even though they virtually lack peroxidase and the ability to iodinate ingested bacteria.

Condition and mass impact oxygen stores and dive duration in adult female northern elephant seals.

The range of foraging behaviors available to deep-diving, air-breathing marine vertebrates is constrained by their physiological capacity to breath-hold dive. We measured body oxygen stores (blood volume and muscle myoglobin) and diving behavior in adult female northern elephant seals, Mirounga angustirostris, to investigate age-related effects on diving performance. Blood volume averaged 74.4+/-17.0 liters in female elephant seals or 20.2+/-2.0% of body mass. Plasma volume averaged 32.2+/-7.8 liters or 8.7+/-0.7% of body mass. Absolute plasma volume and blood volume increased independently with mass and age. Hematocrit decreased weakly with mass but did not vary with age. Muscle myoglobin concentration, while higher than previously reported (7.4+/-0.7 g%), did not vary with mass or age. Pregnancy status did not influence blood volume. Mean dive duration, a proxy for physiological demand, increased as a function of how long seals had been at sea, followed by mass and hematocrit. Strong effects of female body mass (range, 218-600 kg) on dive duration, which were independent of oxygen stores, suggest that larger females had lower diving metabolic rates. A tendency for dives to exceed calculated aerobic limits occurred more frequently later in the at-sea migration. Our data suggest that individual physiological state variables and condition interact to determine breath-hold ability and that both should be considered in life-history studies of foraging behavior.

Measurements of foraging success in a highly pelagic marine predator, the northern elephant seal.

1. Identification of foraging behaviour and the ability to assess foraging success is critical to understanding individual and between-species variation in habitat use and foraging ecology. For pelagic predators, behaviour-dependent foraging metrics are commonly used to identify important foraging areas, yet few of these metrics have been validated. 2. Using the northern elephant seal as a model species, we validated the use of a behaviour-independent measure of foraging success (changes in drift rate) at the scale of the entire foraging migration, and then used this to assess a variety of common foraging metrics that are based on movement patterns and dive behaviour. Transit rate consistently provided the best estimate of daily foraging success, although the addition of other metrics provides insight into different foraging behaviours or strategies. 3. While positive changes in buoyancy occurred throughout most of the migrations, implying successful feeding across much of the north Pacific, the areas of most rapid changes in buoyancy occurred along a latitudinal band (40-50° N) corresponding to a dynamic hydrographic region including Subarctic Gyre and Transition Zone waters. 4. These results support the use of transit rate as an index of foraging success: a metric that is easily derived from tracking measurements on a wide range of marine species.

Texture-Modified Diet for Improving the Management of Oropharyngeal Dysphagia in Nursing Home Residents: An Expert Review.

OBJECTIVES: This paper provides evidence-based and, when appropriate, expert reviewed recommendations for long-stay residents who are prescribed texture-modified diets (TMDs), with the consideration that these residents are at high risk of worsening oropharyngeal dysphagia (OD), malnutrition, dehydration, aspiration pneumonia, and OD-associated mortality, poorer quality of life and high costs. DESIGN: Nestlé Health Science funded an initial virtual meeting attended by all authors, in which the unmet needs and subsequent recommendations for OD management were discussed. The opinions, results, and recommendations detailed in this paper are those of the authors, and are independent of funding sources. SETTING: OD is common in nursing home (NH) residents, and is defined as the inability to initiate and perform safe swallowing. The long-stay NH resident population has specific characteristics marked by a shorter life expectancy relative to community-dwelling older adults, high prevalence of multimorbidity with a high rate of complications, dementia, frailty, disability, and often polypharmacy. As a result, OD is associated with malnutrition, dehydration, aspiration pneumonia, functional decline, and death. Complications of OD can potentially be prevented with the use of TMDs. RESULTS: This report presents expert opinion and evidence-informed recommendations for best practice on the nutritional management of OD. It aims to highlight the practice gaps between the evidence-based management of OD and real-world patterns, including inadequate dietary provision and insufficient staff training. In addition, the unmet need for OD screening and improvements in therapeutic diets are explored and discussed. CONCLUSION: There is currently limited empirical evidence to guide practice in OD management. Given the complex and heterogeneous population of long-stay NH residents, some 'best practice' approaches and interventions require extensive efficacy testing before further changes in policy can be implemented.

The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for early breast cancer delivers 50 Gy in 25 fractions of 2.0 Gy over 5 weeks, but there is a long history of non-standard regimens delivering a lower total dose using fewer, larger fractions (hypofractionation). We aimed to test the benefits of radiotherapy schedules using fraction sizes larger than 2.0 Gy in terms of local-regional tumour control, normal tissue responses, quality of life, and economic consequences in women prescribed post-operative radiotherapy. METHODS: Between 1999 and 2001, 2215 women with early breast cancer (pT1-3a pN0-1 M0) at 23 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy over 5 weeks or 40 Gy in 15 fractions of 2.67 Gy over 3 weeks. Women were eligible for the trial if they were aged over 18 years, did not have an immediate reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 1105 women were assigned to the 50 Gy group and 1110 to the 40 Gy group. After a median follow up of 6.0 years (IQR 5.0-6.2) the rate of local-regional tumour relapse at 5 years was 2.2% (95% CI 1.3-3.1) in the 40 Gy group and 3.3% (95% CI 2.2 to 4.5) in the 50 Gy group, representing an absolute difference of -0.7% (95% CI -1.7% to 0.9%)--ie, the absolute difference in local-regional relapse could be up to 1.7% better and at most 1% worse after 40 Gy than after 50 Gy. Photographic and patient self-assessments indicated lower rates of late adverse effects after 40 Gy than after 50 Gy. INTERPRETATION: A radiation schedule delivering 40 Gy in 15 fractions seems to offer rates of local-regional tumour relapse and late adverse effects at least as favourable as the standard schedule of 50 Gy in 25 fractions.

The accuracy of monthly weight assessments in nursing homes: implications for the identification of weight loss.

BACKGROUND: The prevalence of weight loss is a quality indicator for nursing homes (NH), and monthly weight assessments are conducted by NH staff to determine weight loss. METHODS: A longitudinal study was conducted with 90 long-stay residents in four NHs for 12 study months. Monthly weight values documented in the medical record by NH staff were compared to independent weight values collected by research staff using a standardized protocol. Weight loss was defined according to the Minimum Data Set (MDS) criterion: >or= 5% in 30 days or >or= 10% in 180 days. RESULTS: The total frequency of weight loss episodes per person was comparable between NH and research staff weight assessments across the 12 study months. However, monthly weight values recorded by NH staff were consistently higher than values recorded by research staff, which resulted in a higher prevalence of weight loss and earlier identification of weight loss according to research staff weight values using a standardized weighing protocol. CONCLUSIONS: A standardized weighing protocol improved the detection of weight loss among NH residents and should allow for earlier nutrition intervention.

The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses (fractions). However, a lower total dose delivered in fewer, larger fractions (hypofractionation) is hypothesised to be at least as safe and effective as the standard treatment. We tested two dose levels of a 13-fraction schedule against the standard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size. METHODS: Between 1998 and 2002, 2236 women with early breast cancer (pT1-3a pN0-1 M0) at 17 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy versus 41.6 Gy or 39 Gy in 13 fractions of 3.2 Gy or 3.0 Gy over 5 weeks. Women were eligible if they were aged over 18 years, did not have an immediate surgical reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 749 women were assigned to the 50 Gy group, 750 to the 41.6 Gy group, and 737 to the 39 Gy group. After a median follow up of 5.1 years (IQR 4.4-6.0) the rate of local-regional tumour relapse at 5 years was 3.6% (95% CI 2.2-5.1) after 50 Gy, 3.5% (95% CI 2.1-4.3) after 41.6 Gy, and 5.2% (95% CI 3.5-6.9) after 39 Gy. The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0.2% (95% CI -1.3% to 2.6%) after 41.6 Gy and 0.9% (95% CI -0.8% to 3.7%) after 39 Gy. Photographic and patient self-assessments suggested lower rates of late adverse effects after 39 Gy than with 50 Gy, with an HR for late change in breast appearance (photographic) of 0.69 (95% CI 0.52-0.91, p=0.01). From a planned meta-analysis with the pilot trial, the adjusted estimates of alpha/beta value for tumour control was 4.6 Gy (95% CI 1.1-8.1) and for late change in breast appearance (photographic) was 3.4 Gy (95% CI 2.3-4.5). INTERPRETATION: The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size. 41.6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractions in terms of local-regional tumour control and late normal tissue effects, a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international standard fractionation schedule of 50 Gy in 25 fractions.

Testing the effect of specific orders to provide oral liquid nutritional supplements to nursing home residents: a quality improvement project.

OBJECTIVES: To improve nursing home (NH) staff delivery of oral liquid nutritional supplements between meals to residents with a history of weight loss. DESIGN: Pre-Post intervention study. SETTING: Two skilled nursing homes. PARTICIPANTS: Eighteen long term care residents. INTERVENTION: At baseline all participants had a non-specific physician's order to receive a nutritional supplement. The intervention consisted of specifying the physician's order as follows: "Give 4 oz high protein supplement at 10 am, 2 pm, and 7 pm". MEASUREMENTS: Research staff conducted direct observations for two days during and between meals for a total of 4 days, or 12 possible observation periods per participant before and one week following the intervention. Research staff documented NH staff delivery of snacks (including high protein supplements) and amount consumed (fluid ounces) for the high protein supplements using a standardized protocol during each observation period. RESULTS: Before the specific order was written participants were offered any type of snack an average of 1.82 times per day and a high protein supplement 0.59 times per day. After the specific order was written participants were offered any type of snack an average of 1.59 times per day and a high protein supplement 0.91 times per day. There were no statistically significant differences in the average number of times snacks or supplements were offered before and after the specific order was written. The proportion of snacks offered that were high protein supplements did increase after the specific order was written (p<0.001). When a high protein supplement was provided, most residents consumed 100% of it. CONCLUSIONS: Oral liquid nutritional supplements were not provided consistent with orders in NH practice. The specificity of the order related to type of supplement and time of delivery did not influence when and how often supplements are provided to residents but it did influence the type of nutritional supplement offered.

Production of diglyceride from phosphatidylinositol in activated human platelets.

Human platelets generate diglyceride within 5 s of exposure to thrombin. Production of diglyceride is transient. 15 s after the addition of thrombin, the levels of diglyceride have increased up to 30-fold, but decrease thereafter. Prior incubation of platelets with 2 mM dibutyryl cyclic AMP prevents both the generation of diglyceride and the secretion of serotonin. Acetylsalicylic acid (100 microgram/ml), which completely inhibits prostaglandin endoperoxide synthesis, does not block diglyceride production and serotonin secretion induced by thrombin. Based on studies examining the incorporation of [3H]arachidonic acid into diglyceride of prelabeled platelets exposed to thrombin, it is concluded that neither phosphatidic acid nor triglyceride is the source of the diglyceride. Phosphatidylinositol appears to be the most likely source, both because its loss of radiolabel is sizable and rapid enough to account for the appearance of radiolabel in diglyceride, and because a phosphatidylinositol-specific phosphodiesterase, described in this report, exists in platelets. The phosphatidylinositol-phosphodiesterase, which produces diglyceride and inositol phosphate, requires Ca+2 and shows optimal activity at pH 7. The enzyme does not act upon phosphatidylcholine, phosphatidylethanolamine, or phosphatidylserine.