We present a new experimental study of the quantum entanglement of photon pairs produced in positron-electron annihilation at rest. Each annihilation photon has an energy that is five orders of magnitude higher than the energy of photons in optical experiments. It provides a unique opportunity for controlled Compton pre-scattering of initial photons before the polarization measurements. The experimental setup includes a system of Compton polarimeters to measure the angular correlations of annihilation photons in initial and thus prepared pre-scattered states. For the first time, a direct comparison of the polarization correlations of initial and pre-scattered annihilation photons has been carried out. The angular distributions of scattered in polarimeters photons turned out to be the same for both types of events. Moreover, the correlation function in the Bell’s inequality is also the same for both states. We discuss the implications of our results for quantum measurement theory and for the quantum-entangled positron emission tomography. Such an interpretation of entanglement is quite relevant for the current situation with a system of two photons formed by positron-electron annihilation at rest. The description of this system has been the subject of pioneering work on quantum entanglement in the past century and, as we will see below, is still unclear in some respects.The entanglement of a quantum system is a simple consequence of the superposition principle and means that the state of the system cannot be represented as a product of the states of individual subsystems. Historically, however, this term was introduced by Schrödinger, referring to the entanglement of our knowledge of quantum systems3. He considered at that time a hypothetical bound system of an electron and a positron with an orbital momentum equal to one or zero. In the latter case, due to the conservation of angular momentum and parity, the photons of the pair formed during positron-electron annihilation have mutually perpendicular polarization. In the same article, in order to test the predicted correlation of photon polarization, Wheeler proposed an experimental scheme with two Compton scatterers and detectors of scattered photons, which has already become a classic. Since photons are scattered predominantly perpendicular to the polarization plane, the dependence of the number of registered photons on the angle between the scattering planes should have a maximum and minimum at The study of this two-photon system has a long and remarkable history, which can be divided into several stages. Initially, the idea of measuring a pair of annihilation photons was proposed in 1946 by Wheeler4 and by Snyder et al.5 predicted the behavior of the angular distribution of scattered annihilation gamma rays. It was obtained on the basis of the Klein-Nishina formula6 using the maximally entangled pure state as the initial one:7. Their experimental ratio Almost simultaneously, two theoretical papers by Pryce and Ward8, devoted to the experimental verification of the famous EPR paradox by Einstein, Podolsky and Rosen9. The authors emphasized that positron-electron annihilation with zero orbital angular momentum produces two photons described by the entangled wave function, Eq.  states using the matrix representation of the Klein-Nishina formula. They confirmed the theoretical results10 and concluded that the previous experimental measurements prove the entanglement of system of two initial annihilation photons.Quite recently Caradonna et al.21. Attention is paid to the kinematic restrictions on the angular distributions of scattered gammas in attempts to suppress the scatter and random backgrounds and improve the quality of PET images. In recent years, significant efforts have been made to create working prototypes of PET using the reconstruction of the Compton scattering kinematics. More recently, the research Jagiellonian Positron Emission Tomograph (J-PET)23 was built of plastic scintillators. Identification of double Compton scattering of photons in J-PET plastic bars makes it possible to determine the linear polarization of primary photons and to measure the angular correlations.Strong polarization correlations for annihilation photons in maximally entangled states and the theoretically predicted absence of correlations for separable states motivated the development of a new generation of Positron Emission Tomography (PET), the so-called quantum-entangled QE-PET with Compton scattering reconstruction12, or the Clauser-Horne-Shimony-Holt (CHSH) inequality24 as a particular practical case, has not been applied here. The explanation is quite simple and is related to the low efficiency of Compton polarimeters, which are the only tool for measuring the polarization of high-energy gamma rays. This efficiency is strongly dependent on the energy of gamma-ray and is always less than 0.7 for annihilation photons with an energy of 511 keV. This issue has been discussed by Clauser and Shimony25, who pointed out that entanglement in positron-electron annihilation can only be demonstrated if the polarimeter efficiency is greater than 0.83. In this case, the S-function in the CHSH inequality, reduced to the product of the efficiencies of two Compton polarimeters, would exceed the required limit of 2. In reality, for annihilation photons, this S-function can only reach a maximum of 1.4, since the product of two efficiencies is less than 0.5.The verification of entanglement mentioned above relies exclusively on the angular correlations of scattered annihilation photons. One might wonder why Bell’s theoremS-function was measured in 1996 by Osuch et al.26. They counted the number of scattered photons in Compton polarimeters located at different azimuthal angles. The correlation coefficients were obtained from the coincidence of the count rates between two sets of polarimeters installed on opposite sides of the annihilation photon source. The S-function constructed from these coefficients perfectly reproduces the theoretically predicted behavior:S was well below the required limit of 2. Nevertheless, subsequent corrections for the measured polarimeters efficiencies allowed the authors to state that the CHSH inequality is violated by twelve standard deviations.Nevertheless, the 27, who applied an open quantum formalism to the Klein-Nishina formula and obtained the same Compton scattering cross section for both maximally entangled and separable states of annihilation photons. Since the cross sections of any reactions are of fundamental meaning, their identity for considered quantum states leads to the same angular correlations of scattered photons. This result fundamentally contradict previous theoretical considerations19 and, therefore, claims the incompleteness of existing experimental studies, which are based on the assumed difference in the Compton scattering of photon pairs in maximally entangled and mixed states.The agreement of numerous experimental results with the predictions of quantum theory gives the impression of a complete understanding of the behaviour of a system of two annihilation photons. However, the situation became rather uncertain in 2019 with the appearance of the theoretical work of Hiesmayr and Moskal27 obviously affect the possibility of using quantum entanglement in the development of PET imaging, since it is based on the expectation that parasitic Compton scattering of the initial photon in the body causes the transition of the initial maximally entangled state to a separable one. To resolve apparent theoretical contradictions, Watts et al.28 built a prototype PET with modern semiconductor gamma detectors and a passive Compton scatterer for one of the annihilation photons. They measured the angular correlation of scattered photons for two types of events: initial photons without a passive scatterer and pre-scattered events with a passive scatterer placed in the path of one of the annihilation photons. According to authors, the decohering process in the passive scatterer leads to a separable state with lost entanglement. Unfortunately, the low sensitivity to the measured polarization and large statistical measurement errors did not allow to draw an unambiguous conclusion. New dedicated measurements with intact and pre-scattered states of annihilation photons are required to solve the theoretical puzzle. For this purpose, we have developed a setup29 of Compton polarimeters with a large solid angle and an active intermediate Compton scatterer, which has been operating for about a year and a half at INR RAS. In this paper, we report our measurements of polarization correlations in Compton scattering of initial and pre-scattered pairs of annihilation photons.The results in ref.The principles for measuring the polarization correlations of annihilation photons are illustrated in Fig. Each annihilation photon has an energy equal to the electron mass (511 keV), which is five orders of magnitude higher than the energy of optical photons. Such a sharp difference has both advantages and disadvantages in measuring polarization states. The need to use Compton polarimeters with a relatively low efficiency has already been discussed and makes it problematic to use the CHSH inequality for direct testing the photons entanglement. At the same time, due to the high energy of annihilation photons, one can arrange their interaction/measurement with environment without strong degradation of initial two-photon kinematics. Really, the Compton scattering at any, even a sufficiently small angle, leads to the energy loss of the initial photon. Thus, annihilation photons provide a unique opportunity for direct comparison of polarization correlations for both initial and pre-scattered events, where some energy fraction of initial photon is transferred to the recoil electron.6:E : 30:Using Eq. , the anaAs follows from Eq. , for a g27:31In the case of an entangled pair of photons with mutually orthogonal polarizations, the probability of Compton scattering at scattering angles 29 was constructed to measure the polarization correlation of annihilation photons in both initial and decoherent states. The setup comprises two equivalent arms of Compton polarimeters and a 32. The source is located in a horizontal hole with diameter of 5 mm in a lead cube providing collimated beams of annihilation photons in opposite directions from the source. The positrons from 33. According to the conservation laws of angular momentum and parity the obtained annihilation photons must be in maximally entangled state10.Based on these principles an experimental setupmentclass2pt{minimEach arm of the setup consists of a plastic scintillation scatterer and a ring of 16 NaI(Tl) scintillation detectors of scattered photons with an azimuthal angle between adjacent detectors of 29.The distance between the plastic scatterers is about 70 cm. To produce the pre-scattered photons in a subset of events, an intermediate scatterer , a gadolinium-aluminum-gallium garnet (GAGG) scintillator, with the thickness of 7 mm and transverse dimensions of 15 × 15 mmThe GAGG scatterer is the key element that separates events into two subsets with initial or pre-scattered photons. Therefore, the reliability of interaction identification in the intermediate scatterer is the most important feature of the setup. The timing and amplitude of the signals are used to identify the interaction in the GAGG scintillator and are shown in Fig. The time coincidence spectra of signals from intermediate and plastic scatterers are presented for two cases, with low and high energy deposition in the GAGG. In the first case, the scattering angles in GAGG are small and the influence on the momentum of the initial annihilation photon is minimal. In these events, the noise of the photodetector and readout electronics more strongly affects the time resolution compared to events with higher energy deposition.35 makes it possible to detect recoil electrons with an energy threshold of 2 keV. The permanent energy calibration of GAGG is performed by detecting 170.5 keV energy deposition from photons backscattered by an adjacent plastic scatterer and absorbed in GAGG.Figure The event is recorded in case of coincidence of signals in two plastic scatterers. Such loose event selection allows permanent calibration of detectors and study of background conditions. The photon detection in NaI(Tl) counters and/or in GAGG scatter is identified during the off-line analysis after time and amplitude calibration of all active elements in setup. We define the tagging of events of various types analyzed in polarimeters as follows. A pair of photons is considered in initial state if no interaction is observed in the intermediate GAGG scatterer. Otherwise, the detected energy in the GAGG scatterer means that the photons have undergone pre-scattering.37 particle simulation framework, where the theoretical formula Eq.  detectors of scattered photons, plastic scatterers, and the intermediate GAGG scatterer. Scattering of the initial annihilation photons at The relatively narrow NaI(Tl) energy peak for initial states reflects the range of scattering angles of detected photons. The situation is completely different for pre-scattered events after the interaction of photons with an intermediate scatterer. Even a few percent energy loss (below 30 keV) of the original 511 keV photons in the GAGG scintillator leads to a significant distortion of the energy spectrum. This is the effect of double Compton scattering of the initial annihilation photon in both GAGG and plastic scintillators. After the first scattering in GAGG, the photon deviates within a few degrees from its original direction. Subsequent interaction in a plastic scintillator increases the ranges of scattering angles and energy deposition of photons registered in NaI(Tl).Events with a higher energy deposition in the intermediate scatterer (up to 110 keV) form a complex structure in the NaI(Tl) spectrum. Visible peaks in this energy spectrum correspond to particular cases of the kinematics of Compton scattering. The Monte Carlo simulation of the double Compton scattering of 511 keV photons confirmed that the observed structure in the NaI(Tl) spectrum reflects the kinematics of the first scattering in the GAGG scintillator, which leads to distinct groups of events. These particular cases of Compton scattering and the correlation between energy depositions in the NaI(Tl) and GAGG scintillators are shown in Fig.  In this figure, several distinct groups of events can be identified, labeled as classes “a”, “b”,“c”, and “d”. The double Compton scattering kinematics for these events can be determined using a simple analytical calculation or Monte Carlo simulation. Group “a” represents scattering processes with an electron recoil energy in the GAGG scintillator below 30 keV and, accordingly, with the smallest scattering angles.The range of scattering angles by the GAGG in the “b” and “c” regions is identical and it is larger as compared to the “a”-events. However, events in the “b” region have maximum energy deposition in NaI(Tl) detectors from two sequential Compton scatterings with the first scattering in the GAGG in the direction of the NaI(Tl) counter. In contrast to these events, the “c” group represents a double Compton scattering with the sum of scattering angles exceeding The most complex kinematics of double Compton scattering is observed for the “d” group of events with the lowest energy registered by NaI(Tl). The original annihilation photons in these events pass through the GAGG scintillator without interaction and are backscattered in the plastic scatterer. The second scattering at about 18 with annihilation photons have mainly measured the dependence of the number of counts of scattered photon detectors on the azimuthal angle between these detectors. This dependence is described by Eq. ,,18 with In our experiment, the data set without energy deposition in intermediate GAGG scatterer is associated with initial photons, Eq. . In this see Eq. . Other e see Eq. . For theThe second plot in Fig. To get more information and insight, angular distributions were constructed for all classes of pre-scattered events classified in Fig. R of the numbers of counts for the perpendicular and parallel orientations of the scattering planes, which are very close to each other, From the fitting parameters presented in these plots, one can calculate the ratio The smallest ratio 40. A suitable setup includes two dual-channel polarimeters separating orthogonal linear polarization parallel and perpendicular to some arbitrary R of photons with different spin orientations, the correlation coefficients can be constructed as:The CHSH inequality as a particular variant of Bell’s theorem is used in classical experiments with pairs of entangled optical photonsS-function reaches a maximum of By measuring the correlation coefficients for four different polarimeter orientations, 25, the CHSH inequality is never violated for annihilation photons due to the low efficiency  of Compton polarimeters. To map the real-world experiments with non-ideal polarimeters to the ideal case, the S-function for these two types of events.As discussed by Clauser and ShimonyS-function is straightforward . The elementary Compton polarimeter consists of a scatterer and two orthogonal detectors of scattered photons, as shown in Fig. S-function was determined using four polarimeters with orientations Since in our setup the angle between adjacent detectors of scattered photons is mentclass2pt{minimmentclass2pt{minimp0 are practically identical and coincide with the modulation factors estimated from the angular dependencies of the coincidence counts in the detectors of scattered photons, see Fig. The measured  the Eq.  describi27, while the state of correlations after interaction/measuring of one of the annihilation photons is under theoretical discussion and has not been experimentally determined before. Meanwhile, for some applications, such as the use of quantum entanglement in the next generation of positron emission tomography (QE-PET), it is necessary to know what happens to the correlations after one of the photons interacts with the environment.In this paper, we presented a direct comparison of the polarization correlations of annihilation photons in the initial and pre-scattered states obtained in an experiment with unprecedented statistics. Entanglement in the initial state is predicted in a series of theoretical papers10, the measurement of one of the two initial photons leads to the collapse of the entangled state  polarization with respect to the scattering plane can change to vertical . According to the equation (87.17) in ref.28. The similarity of correlations for the initial and pre-scattered events indicates that most of the scattered backgrounds cannot be rejected by constraints on the angular distribution of scattered photon pairs43. At the same time, the random background obviously has no angular correlations and can be suppressed by applying appropriate kinematic cuts.We hope that our experimental results will help clarify the current theoretical controversy. In any case, the results obtained are directly related to the applicability of quantum entanglement in next-generation positron emission tomography (QE-PET). The pre-scattered events in our experiment accurately reproduce the scattering background in the body, which limits the image quality


The oxygenisotopefractionation associated with this reaction has significant implicationsin the general field of nuclear forensics. Hence, the oxygen isotopefractionation during the reduction of U3O8 toUO2 was determined in the temperature range of 500–700°C and for a duration of 2 to 6 h under a high-purity H2 atmosphere. Three U3O8 samples, possessinga different oxygen isotopic composition, were used to investigatekey parameters involved with the fractionation during the reductionprocess. All UO2 products did not maintain the originalisotope composition of the starting U3O8 underall conditions. The results show that the system UO2–H2O attains isotope equilibrium at 600 °C, provided thereduction process lasts at least 4 h or more. At 600 °C, UO2 was isotopically depleted by 2.89 ± 0.82‰ comparedto the U3O8 from which it was produced. We findthat the H2O formed during the reduction plays a majorrole in determining the final δ18O of UO2 prepared from U3O8. The isotope equilibriumof the system UO2–H2O at 600 °Cwas calculated, indicating that δ18O of the H2O was enriched by about 11‰ relative to the UO2 due to the uranium mass effect. These findings could potentiallyhave important implications for nuclear forensics, as they providea new method for determining the history of UO2 samplesand tracing back their production process.The fabrication of UO The illicittrafficking of uranium from one of the production stages has occurredin the past, attracting significant scientific attention in nuclearforensics. Therefore, an ongoing effort has been dedicated to developingnew analytical techniques, focusing on finding novel signatures toallow improved and credible attribution of uranium compounds foundoutside of regulatory control.Uranium dioxide pellets under a reducing environment ,1 andthe chemical reaction is given in UO3O8 particleswhile conversion proceeds.2 The study ofthe diffusion of oxygen in the natural uraninite–H2O at a temperature range of 50–700 °C suggested an initialextremely fast-path diffusion mechanism that overprints the oxygenisotopic composition of the entire crystal, independent of temperature,and a slower volume-diffusive mechanism dominated by defect clusters.3 Volume diffusion was also considered the primaryprocess controlling oxygen diffusion in polycrystalline and single-crystallineUO2 in the temperature range of 605–750 °C.4 Depth profiling beneath the UO2 pelletsurface at room temperature indicates oxygen diffusion into the UO2 lattice, while water species diffusion occurs along grainboundaries, behaving as high-diffusivity paths.5The mechanism and kinetic model forthis reaction at 510 °Cidentified the rate-limiting step as the desorption of water vaporsfrom the external surface of the U18O/16O—expressed in δ notation asδ18O vs VSMOW) as a signature for geolocation13 and the processhistory18 of uranium oxides for nuclearforensics applications14 have gained muchinterest in recent years. The δ18O variation of naturallyoccurring uranium ore minerals is in the range of −32 to +11‰.8 However, the correlation with local meteoricwater is still in dispute, partially due to the lack of data on thefluid isotopic composition from which the minerals were precipitatedor on post-formation isotope alteration of the original uraninite(UO2).6 On the other hand, it has been documented that uraniumoxides of different geographic origins have significantly different 18O/16O ratios, which correlate with local rainwaterisotopic composition.6The use of the oxygen isotopic composition  on aged U3O8 and UO2. It was suggested that δ18O values of the metaschoepite hydration water are likelyto reflect those of the water vapor to which the sample was exposed.13 Thus, the oxygen isotopes of metaschoepite mineral hydration watermay retain information on the mineral formation location.The comparisonof several oxygen extraction methods from UO19 theoretically investigatedthe fractionation factors α (defined as the isotopic ratio betweentwo compounds) in the systems UO2–H2Oand UO3–H2O over a temperature rangeof 0–1000 °C, finding that uraninite is consistently depletedwith 18O compared to its associated H2O acrossthis temperature range. Yong-fei20 developeda theoretical model to calculate the oxygen isotopic fractionationfactors of metal oxides, including uraninite, over the same temperaturerange. However, the two models20 produced differentresults, with a difference of approximately 10‰ in 1000 lnα (UO2–water) at temperatures up to 300 °Cand a difference of ∼2‰ at higher temperatures between300 and 600 °C. Fayek and Kyser9 foundfractionation factors similar to those reported by Hattori and Halas19 at high temperatures but closer to those predictedby Yong-fei20 at low temperatures.Hattoriand Halas2 from U3O8. UO2 powders were synthesized in the temperaturerange of 500–700 °C for 2–6 h under high purityH2 to follow the process of isotope partition among U3O8 as the source material, UO2, andH2O as products of the reduction reaction.This study focuses on the oxygen isotope change resulting fromthe manufacturing processes of UO23O8 samples with different oxygenisotopic compositions were used as starting materials for this study.Two were synthesized from uranyl nitrate hydrate (UNH). U3O8-I has a δ18O value of 10.68 ±0.27‰, and U3O8-II has a δ18O value of 8.52 ±0.22‰. These two materials weresynthesized by changing the cooling rate to achieve the differencein their δ18O values.17 The third sample, U3O8-III, has a δ18O value of 4.75 ± 0.47‰ and is a natural uraniumcommercial U3O8 material purchased from CETAMA,France , usuallyused as a calibration standard for elemental impurities in uranium.Three U–5 Torr) for 12 h.The samples were calcined for 2, 4, and 6 h at a temperature rangeof 500–700 °C under high purity (99.999%) H2 1 atm, followed by cooling the reactor to room temperature via shuttingdown the furnace. The three U3O8 samples wereplaced together in the reactor  were weighed in an alumina crucibleand placed at room temperature in a stainless-steel furnace beforeapplying a vacuum  and those prepared at 500 °C; 2 h,500 °C; 4 h, and 600 °C; 2 h.XRD analysis  was performed onsamples weighingseveral milligrams under an atmospheric environment by continuousscanning at 40 kV/40 mA in the range of 10–80° at a rateof 2°/min. The analyzed samples were the starting materials  andan IR CO2 laser .The method is described in detail elsewhere.21 Briefly, U3O8 samples (1026–1651 μg), UO2 samples (1240–1700 μg), and SiO2 samples were placed in nickel cups in a stainless-steel chamberand heated overnight at 80 °C under a high vacuum. Pre-fluorinationwas performed thrice for the entire cell with 80 Torr of BrF5. Samples were reacted by laser heating in a 90 Torr of BrF5 atmosphere. The liberated oxygen was purified by liquid nitrogentraps, concentrated on a 5 Å molecular sieve, cooled in liquidnitrogen, and transferred to the mass spectrometer through a gas chromatographcolumn for isotope measurement in a continuous flow mode. The internationalSiO2 standard NBS-28 (δ18O = 9.58‰)22 was used for consistency and calibration ineach batch. The measured values are expressed in δ-notationin peril, relative to Vienna Standard Mean Ocean Water (VSMOW). Thelong-term standard deviation (SD) for NBS-28 was 0.42‰. Allthe samples were run at least in triplicate, and the SD is reportedfor each sample.Oxygen isotopic analysesof the U33.12 and U3O8  and the UO2 samples (3–5 measurements for each sample), prepared at thetemperatures range of 500–700 °C for 2–6 h, andof NBS-28 samples, are presented in 18O valuesof UO2 samples as a function of calcination time are plottedfor each calcination temperature in 18O precision of the UO2 is identical to the routinely measured NBS-28 standards.The average δ3O8 samplein the reduction furnace at 600 °C for 4 h, and the second iswhere the three original U3O8 samples were reactedtogether at different times and different temperatures. δ18O of UO2 obtained from U3O8 of the first group is lower by 2.1, 3.7, and 3‰ than theoriginal values for samples 31UO2, 32UO2, and33UO2, respectively. The results from the second groupshow a general trend of conversion to a common isotope value, whichis unique to each temperature. The difference among samples is largerat a reaction time of 2 h and decreases with increasing reaction time.The samples prepared from U3O8-I and U3O8-II did not retain the original δ18O values and showed a similar trend toward depleted values, whilethe UO2 prepared from U3O8-III presentedan opposite trend toward a small enrichment. At a calcination temperatureof 500 °C for 4 h  at temperatures of 500, 600, and 700 °C. We attributethe partial conversion of U3O8 to UO2 at 500 °C for 2 h to the difference between the closed- versusopen-flow experimental setups.The conversion of Uthe U3O8 1. The co2 does not retainthe original δ18O value of the U3O8 starting materials at alltemperatures and reaction times. Nevertheless, at high temperatures(≥600 °C) and longer reaction times (≥4 h), δ18O converges to a common value when the three starting materialsare reacted together and fully converted, indicating the establishmentof an isotope equilibrium between the reaction products, UO2 and H2O. Thus, the similar δ18O valuesobtained from the three different original materials represent anisotope equilibrium with the generated mixture of the three waters,and therefore, a UO2–H2O fractionationfactor cannot be deduced from combined material experiments.UO2–33UO2 were placed separately at 600 °Cfor 4 h, was conducted to resolve this problem. It allows calculatingthe oxygen isotopic composition of the formed water through mass balanceconsiderations and the fractionation factor between U3O8 and UO2. The isotopic composition of the waterwill be calculated in the next section.A different set of reduction experiments, where samples 31UO4.13O8 to UO2 under an H2 atmosphere.The isotope mass balance equation is given bym represents the massof the material indicated in the parenthesis, and δ18O is its oxygen isotopic composition. The values of the parametersδ18O3O8)(UO in m2)(UO and m2O) U3O8 and UO2 are composed of a singlephase, (2) U3O8 consists of 84.8% uranium and15.2% oxygen by mass, and UO2 consists of 88.1% uraniumand 11.9% oxygen by mass, and (3) during the reduction reaction, U3O8 is fully converted to UO2 and theamount of uranium remains constant. Hence, under these assumptions,1 mg of U3O8 produces 0.9620 mg of UO2 and 0.0428 mg of H2O.The oxygen isotope mass balance can be used to calculatethe oxygen isotopic composition of the formed water molecule, consideringa closed system case where a single sample is converted from U18O2O)(H foreach sample is given byRearranging 18O2O). mf—the mass of the total formed watermolecules (mg). δ18Oi/δ18Oiii/δ18Oiii—δ18O of U3O8-I, U3O8-II, and U3O8-III, respectively (‰). mi/mii/miii—mass of U3O8-I, U3O8-II, and U3O8-III, respectively(mg).We further apply the mass balance calculationto a mixture of 3samples to test our assumptions and calculations. Samples 13UOon above 2. The fi2, 32UO2, and 33UO2. Further, based on 18O value of 16.64± 3.01‰, the theoretical expected δ18O of the UO2 samples is 5.14‰. The measured δ18O values of samples 13UO2, 14UO2, and15UO2 were similar: 5.34 ± 0.34, 5.54 ± 0.27,and 5.55 ± 0.13‰, respectively. We conclude that the finalδ18O of UO2 prepared from U3O8 is determined by isotope equilibrium between the productsof the reduction reaction, UO2, and H2O.The result, 16.64‰, agrees well if we considerthis waterto be a mixture of the previously calculated waters of samples 31UO4.23O8 was fully convertedto UO2 and H2O in our analytical setup, exceptfor the 500 °C and 2 h reaction. Therefore, the fractionationfactor between U3O8 and UO2 cannotbe calculated because these two phases were not sampled along thereaction path and do not co-exist in isotope equilibrium at the finalstage. It is interesting to note that although the two phases, U3O8 and UO2 co-exist, the final δ18O converges to a similar value. This may indicate that theisotope exchange between U3O8, UO2, and H2O is faster than the reduction reaction.The XRD measurementsshow that the initial U18O (Δ18O) between UO2 and H2O can be calculated and the average δ18O value of the calculated formedwater (16.64 ± 3.01‰). The calculated Δ18O at 600 °C in this work is −11‰. This result,where the water is isotopically enriched relative to the solid, canbe explained by the uranium “mass effect” at the first steps of the reaction, where oxygen is being releasedfrom U3O8, to form the UO2 and theenriched H2O. Our experimental results show depletion valuesrelative to the starting materials, which are further supported bythe theoretically calculated Δ18O at 600 °C,published by Hattori and Halas19 and Yong-fei20 .3O8 and the final UO2 , suggesting that the UO2 productsare depleted by ∼ 2.89‰ relative to the initial U3O8 at 600 °C.The average Δ53O8 samples with different startingδ18O values were reduced to UO2 undera high-purity H2 atmosphere at a temperature range of 500–700°C for 2, 4, and 6 h. We find that the final δ18O of UO2 prepared from U3O8 is determinedby the reaction of the formed H2O and the synthesized UO2. The system UO2–H2O reachesisotope equilibrium at 600 and 700 °C in the longer reductiontimes (≥4 h). UO2 products are isotopically depletedrelative to the U3O8 from which they were formedby 2.89 ± 0.82‰ at 600 °C. The H2O formedduring the reaction is enriched by about 11‰ relative to theUO2 due to the uranium mass effect. In nuclear forensicinvestigations, a crucial aspect revolves around understanding therelationship between materials seized outside of regulatory control.Hence, our findings can serve as an additional tool to shed lighton the fabrication process and facilitate material linkage when U3O8 and UO2 are present on the scene.However, additional research is required to comprehensively comprehendthe mechanisms underlying the observed isotope fractionation and tofully exploit this technique in the field of nuclear forensics.Three U


Young adulthood is a key developmental period for understanding outcomes of childhood onset attention‐deficit/hyperactivity disorder (ADHD) and autism. Measurement of functional impairment and quality of life (QoL) can provide important information on the real‐life challenges associated with these conditions. Event‐related potential (ERP) measures from the continuous performance task (CPT) have long been identified as altered in ADHD and autism but the role of these functions in the aetiological pathway to the disorders and associated impact on quality of life in young adulthood is unknown.We investigated the relationships between ADHD and autism, functional impairment, quality of life, and ERP measures from the cued CPT (CPT‐OX) in a young adult twin sample (566 participants aged 22.43 ± 0.96 years old).We observed significant phenotypic correlations between ADHD/autism and lower quality of life with specific genetic overlap between ADHD and physical health, psychological, and environmental aspects. We found significant phenotypic and genetic correlations between ADHD and functional impairment in all domains, as well as between autism and impairment in social functioning and lower impairment in risk‐taking. Both ADHD and autism were associated with attenuated amplitude of inhibitory and proactive control ERPs, with large genetic contributions to the overlap. We also found significant phenotypic correlations between these ERP measures and Weiss Functional Impairment Rating Scale (WFIRS) and QoL.This is the first study to investigate the phenotypic and genetic relationships between ADHD and autism, functional impairment, quality of life and ERP measures in young adulthood. Our findings could represent a step towards identifying ERP measures that are related to behaviour in the absence of overt symptoms. Young adulthood (ages 18–25) is a key developmental period for understanding adult outcomes of childhood onset ADHD and autism. We investigated the relationships between ADHD and autism, functional impairment, quality of life, and event‐related potentials from continuous performance task in a young adult twin sample. We observed significant associations accompanied with significant genetic and environmental overlaps in many cases. First study to investigate the phenotypic and genetic relationships between attention‐deficit/hyperactivity disorder (ADHD) and autism, functional impairment, quality of life (QoL), and event‐related potentials (ERPs) in a young adult twin sample.Decreased QoL in both ADHD and autism. ADHD is associated with increased functional impairment in all domains while autism is associated with higher/lower impairment in social‐functioning/risk‐taking.Both ADHD and autism are associated with abnormal ERPs time‐locked to inhibitory and cue stimuli with large genetic overlap in some. Significant associations between these ERP measures and functional impairment and QoL.The window in development between adolescence and adulthood –young adulthood (ages 18–25) – is critical for understanding adult outcomes of childhood onset ADHD and autism  and person‐first language  when referring to the individuals with high traits on these conditions.Full ethical approval for the study was received from King's College London Psychiatry, Nursing and Midwifery Research Ethics Subcommittee (RESCMR‐16/17‐2673). Data were collected as part of the Individual Differences in EEG in young Adults Study (IDEAS). IDEAS participants were all recruited from the Twins Early Development Study (TEDS), a community sample of over 16,000 twin pairs born in England and Wales between 1994 and 1996 , it was not intended to be a whole community or community representative sample. The sample consisted of 556 participants  with an average age of 22.43 ± 0.96 years (119 Monozygotic (MZ) and 164 Dizygotic (DZ) pairs) : a semi‐structured interview conducted by a trained investigator to assess ADHD symptoms : a semi‐structured assessment allowing observations of social and communication behaviours relevant to the diagnosis of autism. We used module four of ADOS‐2 (designed for adolescents and adults with fluent speech) : a self‐report scale examining adult ADHD‐related impairment with 70 items covering seven domains of dysfunction: family relations, work adjustments, school performance, life skills, self‐concept, social functioning, and risk‐taking. It also provides two metrics of overall impairment: the total mean  and domain mean  : a self‐report questionnaire to assess the quality of life in four domains: physical health, psychological, social relationships and environmental  system . EEGLAB  were removed. An EEGLAB study was then created from these epochs and dipoles located outside the brain or with higher than 15% residual variance were rejected.EEG data were downsampled to 256 Hz, bad EEG channels/time intervals were removed (see Supporting Information for details) and average reference was applied. Independent component analysis (ICA) was applied to each individual recording using Adaptive Mixture ICA (AMICA)  toolbox , common environment variance (c2), and unique environment variance and measurement error (e2). Considering most genetic variance is additive  and dominance (d2) genetics separately, we only used ACE models which will mean dominance genetic variance will go in a2 and therefore a2 reflects broad sense heritability.Twin modelling is based on fitting a genetic model that explains differential correlations observed in twin data by considering the MZ twins share 100% and DZ twins share 50% of their genetic influences while MZ and DZ twins equally share environmental factors  in the analyses. If these are diagnostic measures and only certain extreme groups are included , then in addition we also need to fix the model parameters. We fixed the thresholds, set to the population prevalence of 4% for ADHD  relationships. In these models, age and sex were accounted for as covariates and a random intercept was used to control for twin relatedness . The genetic contribution to this correlation was also significant (64%). While the total phenotypic correlation between autism and risk‐taking was not statistically significant, the genetic contribution was statistically significant (−0.20) Table . This isc2) contributions were highest for FA6 (0.29) and FA2 (0.19)  Figure . While t32) between social QoL and FA2 and FA6 as well as work adjustments and FA1 and FA5 suggested considerable association between ERP factors and these WFIRS and QoL measures independent of ADHD and autism (Table Work adjustment (WFIRS) was phenotypically associated with a broad representation of ERP factors: FA1 (−0.14), FA3 (−0.13) and FA5 (0.12); however, the contribution of genetics to these relationships were not statistically significant. Social relationships (QoL) showed significant negative phenotypic correlations with FA2 (−0.12) and FA6 (−0.10), with significant common environment contributions for FA6 at −0.22 (Rc = 1.00). Social functioning (WFIRS) showed a different pattern of results: a small yet significant relationship emerged between FA4 and social functioning (0.12) , quality of life (QoL), and ERP measures (CPT‐OX task) in 283 young adult twin pairs. Significant phenotypic correlations emerged between both ADHD and autism and QoL in all four domains of physical health, psychological, social relationships, and environment. The association of ADHD and autism diagnosis with lower QoL agrees with previous studies in both autism . The negative loading for the amplitude of cue N2 and the positive loading for cue P3 amplitude at the parietal‐occipital source domain Figure . The enhDespite observing significant associations between ERP measures and ADHD and autism, the effect sizes are small which may limit their predictive value. However, these correlations, remain important despite their small size because they contribute to the understanding of aetiological mechanisms of these disorders. Both ADHD and autism are likely to be determined by numerous factors, each of which makes only a small contribution, which therefore may result in small effect sizes. Considering this, we believe none of these measures will be sufficient for diagnosis of ADHD and autism but could well be considered as aetiologically important in the development of the disorders alongside other measures.A central aim of the study was to investigate associations between ERP indices of the CPT‐OX and WFIRS and QoL. While the CPT‐OX ERPs were broadly related to functional impairment and QoL, evidence for genetic/environmental overlap was limited. Impairment in work adjustments was phenotypically associated with the greatest number of ERP factors  were significant. For example, despite significant phenotypic correlations and substantial genetic associations between autism and physical health (94% and a significant Ra = −0.28) and psychological (85%) QoL, the genetic contributions were not statistically significant, which may be due to the sample being underpowered or it is also possible that this is due to lack of a true effect. The relatively small sample size for a twin study required reduction of the number of tests performed. To find a balance between potential type I and type II errors, variables were preselected for investigation in the twin modelling using multilevel mixed effects models testing for phenotypic relationships (independent of twin relatedness). However, the selection of variables may necessarily exclude information about additional alterations in brain function in the conditions. Since the study sample was enriched for high levels of autistic and/or ADHD traits, we fixed prevalence thresholds and heritability to population values based on representative twin samples. As the estimates are not from the exact same population, but from similar populations, there may be minor influences on the model estimates.While the WFIRS was originally proposed to measure functional impairment for adults with ADHD, which might be used to explain the lack of associations with autism for some domains, this is unlikely given the clear relevance of WFIRS domains for autism. We were unable to investigate comorbid ADHD and autism as a separate group due to the low number of cases with comorbid diagnosis in our sample. It would be of interest to examine the comorbid diagnosis in young adulthood in the future given the evidence for an additive model of cognitive impairments for the comorbid group in childhood .Supporting Information S1Click here for additional data file.


Background: Previous studies have focused on the associations between core symptoms and dietary intake in children with attention deficit hyperactivity disorder (ADHD). However, few studies have explored how dietary patterns and behaviors relate to the risk of ADHD. The aim of our study is to explore the associations between dietary patterns and behaviors and the risk of ADHD, which could provide evidence for follow-up and treatments for children with ADHD. Methods: We conducted a case–control study, including 102 children diagnosed with ADHD and 102 healthy children. The food frequency questionnaire (FFQ) and the children’s eating behavior questionnaire (CEBQ) were used to investigate food consumption and eating behaviors. We applied exploratory factor analysis for constructing dietary patterns, and the factor scores were adopted for log-binomial regression to assess the associations between how dietary patterns and eating behaviors affect the risk of ADHD. Results: We extracted five dietary patterns with a cumulative contribution rate of 54.63%. Processed food–sweets scores revealed positive associations with an increased risk of ADHD . Moreover, processed food–sweets tertile 3 was associated with an increased risk of ADHD . In terms of eating behaviors, the group with a higher score relating to a desire to drink was also positively correlated with the risk of ADHD . Conclusions: In the treatment and follow-up of children with ADHD, dietary intake and eating behaviors should be considered. Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood, and it is characterized by age-inappropriate inattention, hyperactivity, and impulsivity . It has It is worth noting that children with ADHD are more likely to suffer from dietary intake problems, such as unreasonable nutrient intake, disordered dietary structures, and poor eating behaviors ,8. DietaAs a significant approach for children to receive nutrition, food intake can be considered largely affected by eating behaviors. Available evidence shows that children with ADHD are accompanied by more unhealthy eating behaviors, and emotional or overeating may be triggered by hyperactivity or impulsivity. For example, food addiction/overeating was significantly associated with ADHD diagnoses in both children and adults and may be an important variable in the relationship between ADHD and obesity . AddictiIn this research, we designed a case–control study and applied factor analysis to investigate the associations between dietary patterns and eating behaviors with the risk of ADHD. We hypothesized that certain dietary patterns or behaviors might be associated with the increased risk of ADHD. Our study not only provides evidence for the follow-up and treatments of ADHD, but also supports references for correcting growth deviations in children with ADHD.This is a case–control study with a matching design that includes children who visited the Department of Children Health Care from June 2020 to December 2020. The case group included 102 children who were diagnosed with ADHD by the attending physicians or above in the psychological–behavioral clinic. The inclusion criteria for the case group are as follows: (1) age 6–13 years. (2) First visit and meeting the diagnostic criteria for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) [In this study, food frequency questionnaires (FFQs) were used to investigate the frequency and total intake of various food types. The questionnaires were designed by a panel of experts, including scientists in the fields of epidemiology and nutrition . In the In addition, the Children’s Eating Behavior Questionnaire (CEBQ), developed by Jane Wardle et al., was used to evaluate children’s eating behaviors . It is wPhysical measurement technicians measured the height and weight of the children and the parents, with an accuracy of 0.1 cm for height and 0.01 kg for weight, and the body mass index (BMI) was calculated. In addition, the participants completed the self-designed questionnaires under the guidance of the investigators, which included demographic characteristics, parents’ education level, annual family income, and the parent–child relationship. These covariates were taken into account in the analysis.25, P75), and the Mann–Whitney U test was used to compare the difference between the groups. The qualitative data are represented by frequency (%), and s Chi-square test was used to compare the groups.Epidata3.1 was used to input the questionnaire and scale the data. Continuous data that followed a normal distribution are expressed as mean ± standard deviation, and an independent sample t-test was used to compare the differences between the subjects with ADHD and the controls. The non-normal continuous variables are expressed as median (Pp < 0.05). Secondly, common factors were extracted based on principal component analysis, and five common factors were determined based on the dietary pattern, with a factor load coefficient > 0.35. The extracted common factors were further rotated by the maximum variance method to achieve a simpler structure and better interpretation, where a positive loading indicates a positive association between a given food and the pattern, while a negative loading indicates a negative association with the pattern. The factor loading represents the correlation coefficient between each food and the dietary pattern, reflecting the importance of each food in the dietary pattern; that is, foods with a high absolute load are considered to be the main factor of the dietary pattern. Next, the variance contribution rate of each factor was calculated, which is an index to measure the importance of the common factors.Exploratory factor analysis was used to construct the dietary patterns of 18 food consumption categories obtained by the FFQ. It is mainly based on the principle of dimensionality reduction, exploring the correlation coefficient matrix between different food types and grouping by the correlation size of various foods so that the correlation between the foods in the same dietary pattern is high, while the correlation between the foods in different dietary patterns is low. Firstly, the Kaiser–Meyer–Olkin (KMO) test and Bartlett sphericity test were performed to evaluate whether factor analysis was appropriate  and the odds of ADHD. The tertiles divide a sequence of numbers into three equal parts, including low-value (Tertile 1), medium-value (Tertile 2), and high-value (Tertile 3) groups. A p < 0.05, indicating that there was a significant correlation between the analyzed variables; therefore, it is suitable for factor analysis. A total of five dietary patterns were extracted, namely coarse grains–poultry–vegetables , processed food–sweets , dairy–seafood , fruits–nuts , and staple foods . The variance contribution rate of each factor was calculated by dividing the square sum of each factor load by the number of variables, which was used to measure the importance of common factors. Overall, the five dietary patterns cumulative variance accounted for 54.63% . In addition, when the scores were converted to tertiles, the risk of ADHD was increased in the tertile 3 group . We also found that the risk of ADHD was significantly increased in the tertile 3 group with staple food patterns   Figure .Since the eating behavior scores did not conform to a normal distribution, the Mann–Whitney U test was applied to analyze the differences between the ADHD and control groups. No differences were found between the two groups of children in terms of food-avoidant behaviors, while regarding the food approach dimension, ADHD children showed significantly higher “desire to drink” scores compared to the controls .In addition, the association between eating behavior characteristics and ADHD risk was examined, and no significant association was found between the eating behavior scores and ADHD risk. The children were divided into two groups based on the median score; the risk of ADHD was associated with the upper median group on the dimension of “desire to drink”, and there were no differences in the other dimensions  Figure .The daily intakes of nutrients obtained from the 24 h dietary review were compared between the two groups. It was found that the daily intakes of energy, fat, carbohydrate, iodine, and nicotinic acid in the ADHD group were significantly higher than those in the control group .In our study, five mainstream dietary patterns were identified to investigate eating behaviors in children. A processed food–sweets pattern rich in processed meat, fried food, puffed food, sugared beverages, and candies was positively associated with ADHD. The staple food pattern of flour products, rice products, and eggs was also associated with an increased risk of ADHD. In addition, in terms of eating behavior, the desire to drink in the food approach dimension was also positively associated with ADHD. Therefore, the findings validated the consistency of processed food–sweets dietary pattern and desire to drink behavior. To our knowledge, we are the first group to combine dietary patterns and eating behaviors to explore their relationship with ADHD after identifying risk factors separately and then mutually validating each factor. Clinicians and researchers are expected to explore comprehensive interventions for dietary structure and behaviors in order to achieve greater benefits.Our study found that processed food–sweets scores were associated with the risk of ADHD diagnosis. Similarly, in a study of Iranian children, adherence to fast food and sweet dietary patterns was associated with a higher prevalence of ADHD , and simThe daily intakes of energy, carbohydrate, and fat in the ADHD group were significantly higher than those in the control group, which was consistent with the “processed food-sweet” dietary pattern. Carbohydrates include all kinds of sugars, and the intake of sweets may account for a large proportion in this population. In addition, processed food is often high in energy and fat, which may be associated with increased daily energy and fat intake in children with ADHD . In addiThe FFQ was used to obtain the frequency and quantity of various foods consumed by ADHD children before the study period. It has the advantage of understanding dietary patterns and habits compared with short-term diet reviews. However, the results may not be accurate due to the fact that the report is recalled. The 24 h dietary review was a dietary log filled by the ADHD children and parents. The weight of various foods was calculated by the nutritionist, and the dietary nutrition analysis software calculated the energy intake and nutrient content of children’s daily diets, which may be more accurate. Therefore, the two evaluation methods were combined in our study. Among the evidence between eating behaviors and ADHD diagnosis, a longitudinal study suggested that food responsiveness was an early marker of ADHD symptoms at 6 years of age . In contThe major strengths of this study included the fact that the ADHD cases were first-time visits without any medication or other intervention, as the use of certain medications would affect children’s appetite, which would also lead to changes in dietary intake. Secondly, all of the assessments were conducted on outpatients by trained psychologists and dietitians, with high compliance and producing good-quality information. Thirdly, the FFQ combined with factor analysis summarized dietary patterns, which represented a broader picture of food and nutrient consumption, so it was more valuable than single food or nutrition in predicting disease risk, which also showed that the results were reliable and stable. Finally, it was found that the “processed food-sweet” dietary patterns and “desire to drink” eating behaviors were both associated with the risk of ADHD in children.There were some limitations in our study. Due to the cross-sectional design, the causal relationships between dietary intake, behavior, and a diagnosis of ADHD could not be obtained, and patients with eating disorders could not yet be identified, as these need to be confirmed in a longitudinal study. Other possible confounders associated with ADHD and dietary intake, such as labor complications, breastfeeding, and household composition, cannot be ignored  and requThis case–control study found that processed food–sweets and staple foods were significantly associated with an increased the risk of ADHD, as was the desire to drink behavior. Therefore, improving health education related to eating behaviors and dietary patterns might be an effective and practical method for ADHD prevention and control among Chinese children. It is worth further investigating causality and determining whether dietary manipulation helps improve the core symptoms. In summary, we suggest that attention should be paid to diet and behavioral management in the treatment and follow-up of children with ADHD to reduce the risk of dietary factors on the core symptoms of ADHD as well as growth and development.


Bartonella infection and its genetic diversity in rodents in Beitun, Xinjiang Uygur Autonomous Region, China. Small mammals were captured using snap traps at four sampling sites in 2018. Spleen and liver tissues were collected and cultured to isolate Bartonella strains. Whole-genome sequencing was performed on the strains identified as Bartonella by gltA gene PCR, and the average nucleotide identity (ANI) of the genomes was calculated by using FastANI v1.33. Phylogenetic trees were constructed for the samples positive for Bartonella spp. by the gltA PCR assay based on 1,290-bp gltA genes, 2,903-bp rpoB genes, and core-genome single nucleotide polymorphisms (SNPs). Among 66 rodents, 11 were positive for Bartonella, with an infection rate of 16.67%. The rodent infection rates in different tissues , species , and habitats  did not show statistical differences. Bartonella spp. isolated from the rodents were phylogenetically divided into six clades (two different Bartonella species were detected in two rodents). By comparing phylogenetic trees based on gltA genes, rpoB genes, and SNPs, we found that the topological structures of several evolutionary trees are different. However, the Bartonella strains isolated in this study were clustered into six clusters in different phylogenetic trees. Broad distributions and high genetic diversity of Bartonella strains were observed among rodents in Beitun, Xinjiang.In this study, we investigated IMPORTANCE Rodent-borne Bartonella species have been associated with zoonotic diseases. Bartonella species such as Bartonella elizabethae, Bartonella grahamii, and Bartonella tribocorum can cause disease in humans. Humans can be infected by blood-sucking arthropods through the scratches and bites of an infected reservoir host or via contact with infectious rodents. Xinjiang is one of the provinces with the most abundant species of Bartonella in China, but there are few reports about the prevalence of Bartonella in the Beitun area. This research aims to investigate the occurrence and prevalence of Bartonella infection in rodents at these sampling sites and provide a basis for the prevention and control of rodent Bartonella species in Beitun and the surrounding areas of Xinjiang. Bartonella was previously classified as Bartonella, Grahamella, Rochalimaea, and alphaproteobacteria. These microorganisms are aerobic, Gram-negative, facultative intracellular parasitic, and slow-growing pleiomorphic organisms , including over 20 species that have been isolated in wild rodents   . Since mrtonella .Bartonella infections in rodents have been reported in at least four neighboring countries , followed by Rattus norvegicus (n = 10), Mus musculus (n = 9), Meriones tamariscinus (n = 7), Cricetulus migratorius (n = 5), and Meriones meridianus (n = 2). One Dryomys nitedula rodent and one Microtus gregalis rodent were captured.A total of 66 rodents belonging to 8 species and 7 genera from 3 rodent families were captured at 4 sampling sites . Thirty-Bartonella in rodents was 16.67% (11/66), but there were no significant variations in infection rates  among the 8 species  from 66 liver and 9 (13.6%) from 66 spleen samples, and there were no significant variations in infection rates  , 44.4% (4/9), and 16.7% (1/6), respectively. Animals captured in two habitats, the shelterbelt forest and grassland, did not develop Bartonella infection. There was no statistically significant difference  in the positivity rates for the five habitats.The prevalence of  species . Thirteee test]) . The culBartonella DNA was performed using gltA PCR. DNA sequence homology analysis and phylogenetic analysis indicated that six Bartonella species were detected in the spleens and livers of rodents. Different species of Bartonella were isolated from the spleens and livers of animals 70 and 73 . B. grahamii (1 isolate), B. grahamii-like (2 isolates), B. tribocorum-like (3 isolates), B. elizabethae-like (1 isolate), and B. krasnovii-like (2 isolates) isolates and isolates of unknown genotypes (4 isolates) were obtained from Apodemus uralensis, Cricetulus migratorius, Meriones tamariscinus, and Meriones meridianus from Beitun, Xinjiang. Animals 70 and 73 were coinfected with a B. krasnovii-like isolate (ML70XJBT) and an isolate of an unknown genotype (MM73XJBT)  .Bartonella isolates from Beitun rodents with recognized species of Bartonella, we performed phylogenetic analyses based on the full-length gltA and rpoB genes. In the phylogenetic trees of the sequences  were divided into cluster VI. By comparing the topological structures of the three evolutionary trees, the Bartonella isolates obtained in this study were divided into six clusters, but there were differences in the details of the evolutionary trees , with numbers of CDSs ranging from 1,998 to 2,347. All of the strains obtained in this study contained one predicted tmRNA (transfer-messenger RNA), but the predicted number of tRNAs was between 39 and 44, and the predicted number of rRNAs was between 3 and 4. The number of rRNAs predicted for CM31XJBT alone was 4 , are presented in ne was 4 . Under aBartonella were used to assess the overall genome similarity . AU4XJBT showed an ANI of >97%, compared to B. grahamii, which had the highest value (97.85%) found. The whole-genome ANI of AU5XJBT was calculated in relation to phylogenetically related species: ANI values of 99.55% and 99.99% were found compared to AU15XJBT and AU16XJBT, respectively. The three strains belonged to the same species and had the highest ANIs with B. tribocorum strain CIP 105476 . Similarly, ML70XJBT and MM73XJBT.G belonged to the same species , and ML69XJBT belonged to the same species as ML71XJBT and MM73XJBT . AU55XJBT and B. elizabethae had the highest ANI (93.22%) compared with the other Bartonella species analyzed. AU18XJBT and CM31XJBT had the highest ANIs (94.60% and 94.44%) with B. grahamii, respectively (Table S1).The average nucleotide identity (ANI) values of the 13 strains obtained in this study and 39 strains downloaded from the National Center for Biotechnology Information (NCBI) database for the genus milarity –13. The Bartonella strains in this study and 39 other Bartonella strains   were clustered. AU55XJBT from A. uralensis had the highest similarity to B. elizabethae and B. kosoyi. The B. krasnovii clade included ML70XJBT from M. tamariscinus and MM73XJBT.G from M. meridianus. This analysis, based on SNPs in genomic sequences, showed that the ML69XJBT, ML70XJBT.G, ML71XJBT, and MM73XJBT isolates from Meriones were grouped  . Fewer S grouped . We obseBartonella were detected in four rodent species. Among them, B. grahamii was reported to be able to cause neuroretinitis in humans  of the 13 strains isolated in this study were different, especially those with ANI values of <95%. In general, an ANI value of <95% is used as a cutoff point for determining new species . On the other hand, it may be due to gaps in the assembled genome. More Bartonella sequences are needed to verify whether there are different results of the phylogenetic analyses of the draft genome and the complete genome.In this study, the species of  species  and 4. H species , 12, 20.proposed . AccordiBartonella . They were highly similar to “Candidatus Bartonella gerbillinarum” (99.69% to 100%) by 320-bp gltA gene alignment. Comparison of the full-length gltA genes  showed that B. alsatica had the highest similarity (90.28% to 90.51%) with these strains. B. taylorii had the highest similarity (91.04% to 91.26%) with these strains by comparison of the full-length rpoB genes . All values were below the threshold of 97%. Phylogenetic trees based on SNPs in the core genome showed that the four strains mentioned above were closest to B. florencae R4. At the whole-genome level, the four strains had the highest ANIs (85.95% to 86.12%) with B. florencae R4, which did not reach the cutoff value that could accurately identify the species. These results indicate that ML69XJBT, ML70XJBT.G, ML71XJBT, and MM73XJBT may potentially be new species of Bartonella. The ANI values of ML70XBT.G and the other three strains were between 93.65% and 93.76%, suggesting that ML70XBT.G might be a subspecies.In this study, we could not accurately identify four strains of Bartonella burdens. These and previous observations suggest that the long-term persistence of Bartonella in these tissues may damage these organs  gene with the universal primers shown in Rodents were captured using the trap-at-night method in June 2018 in Beitun and surrounding areas of the Xinjiang Uygur Autonomous Region . Traps baited with peanuts were set up in three regions consisting of five habitats, an ng sites . Morphol2 at 36.5°C for 20 days. Next, we selected suspected Bartonella organisms for purification and passage 2 to 4 times.Approximately 10 mg of organ samples (liver or spleen) was added to 2-mL centrifuge tubes with 100 μL of tryptic soy broth (TSB) (BD) and some 1.2-mm grinding beads and disrupted using a Dounce-Potter homogenizer under sterile conditions, and the suspensions were inoculated onto tryptic soy agar (TSA) (BD) plates containing 5% defibrinated sheep blood. Plates were kept in a humid environment with 5% COg at 4°C. The supernatant was used as a DNA template for PCR. The initial screening of Bartonella DNA was performed using PCR to detect a portion of the citrate synthase gene (gltA) with the primers BhCS.781p and BhCS.1137n  according to the manufacturer’s instructions. Genomic DNA was extracted by using SDS , followes v3.8.0 . The seqs v3.8.0 .http://blast.ncbi.nlm.nih.gov/Blast.cgi) to determine splicing sequence similarity values. Bartonella isolates were considered similar to validated Bartonella species if the gltA fragments had ≥97% sequence similarity . Gene sequences were aligned using ClustalW. A phylogenetic tree was created by using the maximum likelihood (ML) method in Mega_X_10.1.8 with 1,000 bootstrap replicates. The best evolutionary model was selected by the Models program in Mega_X_10.1.8.The DNAStar Lasergene SeqMan  procedure was applied for sequence splicing, and a BLAST search was performed (milarity . The fulBartonella isolate genomes (this study) were compared with 39 published Bartonella genomes with valid names retrieved from the National Center for Biotechnology Information (NCBI) RefSeq database (Bartonella genomes were not included in the RefSeq database (Bartonella genomes mentioned above were compared. Single nucleotide polymorphisms (SNPs) in the core genomes were found using Roary v1.13.0 (Pairwise average nucleotide identity (ANI) values were estimated using FastANI v1.33 . The resdatabase , but somdatabase  and 5. A v1.13.0  analysis v1.13.0  and weregltA gene was used for the preliminary identification of Bartonella species obtained in this study, an interesting phenomenon was found: different species of Bartonella were cultured from the spleen and liver tissues of animals 70 and 73. To verify the presence of two Bartonella coinfections in rodents 70 and 73, tissue samples from these two animals were recultured. In this Bartonella isolation experiment, we selected as many monoclonal bacteria as possible from the primary culture medium for passage culture. Next, the appropriate numbers of colonies were selected from the purified culture medium to prepare a DNA template for PCR, and the gltA gene was then amplified for identification.When the P value of 0.05.R v4.1.2 was used for statistical analysis, with the significance level set at a Bartonella species were downloaded from the NCBI public database on 1 July 2022. All publicly available assemblies were subjected to quality control by using Quast v5.0.2 (N75 values of <10,000 bp and >500 undetermined bases per 100,000 bases were discarded (Bartonella species downloaded from the NCBI that were included in this genomic analysis.The assembly genome sequences of validly named t v5.0.2 . Genomesiscarded . Table 5Bartonella strains have been submitted to the NCBI GenBank database under accession numbers JAQNDQ000000000, JAQITG000000000, JAQITF000000000, JAQNDP000000000, JAQITE000000000, JAQITC000000000, JAQITD000000000, JAQITB000000000, JAQISX000000000, JAQITA000000000, JAQISZ000000000, JAQISY000000000, and JAQISW000000000.The novel genome sequences of the


The two most prevalent neurodevelopmental disorders—Attention Deficit Hyperactivity Disorder (ADHD) and Autism (ASD)—(ASD/ADHD) strongly impact individuals’ functions. This is worsened when individuals are undiagnosed and risks such as increased imprisonments, depression or drug misuse are often observed. This systematic review synthesizes the risks associated with late/undiagnosed ASD/ADHD.Four databases were searched . Published studies exploring the impact of undiagnosed ASD/ADHD were included. Exclusion criteria included, lack of diagnosis status, studies not solely on ASD or ADHD, gray literature and studies not in English. The findings were summarize through a narrative synthesis.Seventeen studies were identified, 14 on ADHD and three on ASD. The narrative synthesis identified three main themes: (1) Health, (2) Offending behavior, and (3) Day-to-day impact. The risks highlighted a significant impact on mental wellbeing and social interactions, higher risks of substance abuse, accidents and offending behavior as well as lower levels of income and education.The findings suggest that undiagnosed ASD/ADHD is linked to many risks and negative outcomes affecting individuals, their families, and the wider society. The restricted number of studies on ASD are a limitation to the generalization of these findings Implications for research and practice are discussed, highlighting the importance of screening and acknowledging the possibility of ASD/ADHD in many settings such as psychiatric and forensic. Neurodevelopmental disorders including Attention Deficit hyperactivity disorder (ADHD), autism (ASD), dyspraxia and tic disorders, affect around 6% to 8% of the adult population . They arIndividuals with ASD and/or ADHD (henceforth ASD/ADHD) report difficulties in obtaining appropriate support, diagnosis, and treatment for difficulties associated with their conditions . This leThese considerable risks are attenuated when ASD/ADHD are diagnosed, as diagnosis facilitates access to care or support . For insThere are multiple reasons why many children and adults are still undiagnosed. Socio-economic factors often play a role in recognition of ASD/ADHD. The gender perception gap in how these conditions are expressed and impact males and females for instance can bias recognition, as girls are often missed . AdditioWhile there is a wealth of knowledge regarding how ASD/ADHD impacts the lives of individuals, little is known about the traits of adults with ASD/ADHD who are undiagnosed or about the human costs incurred by the disorder among these people. This systematic review identifies and synthesizes the risks associated with late/undiagnosed ASD/ADHD reported in the published literature. No synthesis of these risks has been conducted to date and these novel findings may help to inform future research and policy development.This review was written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) guidelines . A protoSupplemental Material as an example and included terms such as: Attention Deficit Disorder with Hyperactivity/(ADHD or ADDH or “attention deficit disorder*” or “attention deficit hyperactivity disorder*” or “hyperkinetic disorder*”), exp Autism Spectrum Disorder/(autis* or ASD or ASC or asperger*). Adaptation of the MEDLINE search strategies was made for the other databases according to their own search criteria. The search was performed on the 5th of December 2022, date limits were not imposed. While hand searching was not a strong component of our planned search strategy, the reference lists of all papers that meet the inclusion criteria were hand searched to check for any additional studies.Four databases  were searched. PROSPERO was checked for ongoing or already published systematic reviews on the subject. A full search strategy for Medline (MEDLINE In-Process & Non-Indexed Citations and OVID MEDLINE 1946 to present-Ovid) is detailed in Quantitative and qualitative studies were included. The qualitative component of this review considered qualitative studies of any design exploring the impacts, effects or risks associated with undiagnosed ADHD/ASD . The quantitative component of this review included quantitative studies of experimental and observational designs . Mixed method studies were also included, relevant qualitative and quantitative components extracted separately. Studies published in peer-reviewed publications were solely considered.This review covers studies examining individuals (adults and children) who have not yet received a diagnosis of ASD/ADHD but show traits/symptoms of these disorders on validated screening and assessment tools . If studies included multiple groups such as diagnosed and undiagnosed individuals, undiagnosed findings were extracted and reported separately. Studies where individuals are on the care pathway to get a diagnosis as well as studies looking into untreated/unsupported ADHD/ASD were included if the reason for lack of treatment was due to lack of diagnosis.This review is examining the impact of not receiving a diagnosis of ADHD/ASD when symptoms of ASD/ADHD are present and meet diagnostic or screening criteria. Within the context of this study, impacts are defined as any consequence from having these conditions in daily life and include consequences to the individuals, their environment , their families and any others impacted. This definition and concept of impact vary between each study therefore this review looked at broader concepts such as risks, effects, or consequences. This review considered studies focusing on ADHD/ASD throughout the lifespan and therefore included studies of children, adolescents, and adults.This review was conducted in any setting and took an international perspective. The period of the review was not restricted, covering all publications from inception up to the 5th of December 2022.Unpublished and gray literature were excluded. Studies were also excluded if they did not specify the status of diagnosis examined or focusing on diagnosed individuals and studies that do not mention the terms “Attention Deficit Hyperactivity Disorder,” “Autistic,” “ADHD,” “Autism” or “ASD.” Case studies and studies on genetics, medication and scale development were excluded as well as studies not published in English. Studies that did not separate findings from undiagnosed and diagnosed groups were also excluded.Supplemental Material S1. The study selection process is presented in Following the search, all identified citations were uploaded into a reference manager software (Zotero). Two of the review authors independently screened the titles and abstracts for assessment against the search inclusion criteria (BF and DD). Full reports were obtained for all titles that appear to meet the inclusion criteria. The same two review authors screened and assessed the full text reports in detail against the inclusion criteria. Disagreement on selected studies were resolved through discussion and/or presented to a third reviewer (SC). Studies that do not meet the inclusion criteria were excluded and a record of reasons for excluding studies can be found in The lead reviewer (BF) extracted qualitative and quantitative data from the included studies using a standardized data extraction tool . The datThe main outcome is the synthesis of risks associated with having undiagnosed ADHD/ASD. Multiple types of factors reported in the selected studies were evaluated such as societal factors  and health factors . These factors were grouped into themes within the synthesis phase.Due to the mixed-method nature of this review, a segregated synthesis is proposed where two distinct analyses of qualitative and quantitative evidence were made prior to conducting a mixed-methods synthesis .A meta-synthesis summarized the qualitative findings. This aggregation or synthesis of findings generated a set of statements representing the aggregation and categorizing them based on similarity in meaning. The findings were presented in narrative form. As statistical pooling was not possible for quantitative data, the findings were presented in a narrative form including tables and figures. The two analyses were then aggregated and combined in the form of qualitative themes . Two revFollowing mixed methods reviews guidelines , the proThe studies included in this review give an international view of the topic discussed with studies from nine different countries . The most common mental health reported difficulties were depression and anxiety but also included psychiatric inpatient admissions and suicidality. These mirror previous findings on the impact of lack of diagnosis on mental health . In a reOffending behaviors including imprisonment, aggression, criminality, and substance abuse were also a key theme from this review. These results reflect findings from many studies which have shown that high rates of prisoners have undiagnosed/untreated ADHD . ADHD isThe day-to-day impact of undiagnosed ASD/ADHD included many risks across different settings. These encompassed social difficulties and difficulties in relationships, difficulties with money, education and work as well as driving. Undiagnosed ADHD was consistently linked to lower income and lower educational attainment. While this impact was not researched directly in any of the studies, six studies demonstrated this as a key additional finding through demographic questionnaires. While these findings mirror current knowledge on the relationship between ADHD and lower educational outcomes , our revThis review demonstrates that the risks associated with undiagnosed ASD/ADHD are significant, greatly impairing and need to be taken seriously. While the rates of ASD/ADHD diagnosis has increased in the past decade  and the This review contains some strength and limitations. To the authors’ knowledge, this is the only review that has attempted to establish the specific risks and impacts arising from a lack of ASD/ADHD diagnosis. This review included all studies looking specifically at this topic, regardless of age group and the limited number of included studies suggest that this is an under-researched or difficult to study topic. The main limitation of this review is the small number of studies on ASD. Despite the similarity of topics between the ASD studies and the ADHD studies, with only three included studies on ASD, it is not possible to generalize or indeed differentiate the findings across disorders. While most studies conducted a thorough assessment of ASD/ADHD as part of their methodology (including but not limited to interviews and questionnaires), a few relied solely on screening questionnaires. While these may give a strong inclination of individuals having ASD/ADHD, they are limiting as no official diagnosis process was performed. Similarly, our search criteria aimed to specifically identify groups of “undetected,” “undiagnosed” and “unrecognized” ASD/ADHD. Studies which might have used different terminology would not have been capture by our search or identified in our review of titles, abstract or keywords. This was intentional to limit the number of non-relevant studies or studies where undiagnosed ASD/ADHD was not a key focus, however this may explain the limited number of ASD relevant studies, as many studies tended to assess autistic traits across a whole population, rather than identify a specific group of undiagnosed autistic people. Additionally, a few studies on undiagnosed ASD were excluded due to a lack of separate report of the findings which prevented us to draw conclusions on this population.A few recommendations can be made from this review, both on the clinical and research impacts of the findings. Understanding the psychosocial burden of undiagnosed ASD/ADHD will help teachers, clinicians, and policy makers pay more attention to the consequences of under-diagnosis of these conditions. Due to the high rate of undiagnosed ADHD in specific healthcare services such as emergency services (for accidents and injuries), psychiatric services  and forensic services (for substance misuse and prisons), it would be advisable that healthcare professionals in these settings regularly screen for potential ADHD, using standardized screening measures such as the adult ADHD self-report scale ASRS-  or the CClick here for additional data file.Supplemental material, sj-rtf-1-jad-10.1177_10870547231176862 for Risks Associated With Undiagnosed ADHD and/or Autism: A Mixed-Method Systematic Review by Blandine French, David Daley, Madeleine Groom and Sarah Cassidy in Journal of Attention Disorders


Separate studies with clinical and community‐based samples have identified an association between symptoms of attention‐deficit hyperactivity disorder (ADHD) and inhibitory control deficits and ADHD and weak effortful control. We tested whether differences in effortful control explained the associations between ADHD symptoms and inhibitory control deficits, controlling for conduct problems. In a community sample, parents rated ADHD symptoms, conduct problems, effortful control, surgency and negative affect in 77 4‐7‐year‐olds (47 girls), who performed an inhibitory control task. ADHD symptoms, deficient inhibitory control and low effortful control were correlated. Controlling for conduct problems, path analysis showed the ADHD symptoms – inhibitory control link was mediated statistically by effortful control. This focuses attention on cognitive‐energetic factors associated with ADHD‐related executive deficits. Inhibitory control (IC) has been singled out as primary executive function (EF) affected in ADHD.ADHD symptom are linked to low effortful control, a temperament factor that conceptually overlaps with EF.Conduct problems (CP) that often cooccur with ADHD, are also linked to temperament differences.After controlling for CP, ADHD symptoms‐IC link was fully statistically mediated by effortful control.In contrast, CP were directly associated with poor IC.The nature of IC deficits may be unique to the type of psychopathology.Attention‐deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition characterized by persistent and age‐inappropriate hyperactivity, impulsivity and inattention, which disrupt daily functioning and may interfere with healthy development. ADHD is characterized by heterogeneity in neurocognitive deficits and a diverse range of behavioural symptoms, which vary by sex and developmental stage and are often accompanied by emotional difficulties  while also accounting for conduct disorder, showed that these psychopathologies were characterized by specific temperamental and regulatory profiles  and their parents were recruited from an urban location in the United Kingdom. A further eight children took part but were excluded from the study . Parents and children were recruited from the database of families who expressed interest in taking part in developmental research and via social media advertisements. Although participating families represented diverse ethnic communities, the sample was particularly well‐educated, with 78% reporting having a university degree (Table A convenience sample of 77 children (30 boys) aged from four to 7 years  with a fruit (watermelon or orange) according to the rules provided by the experimenter. For example, ‘Sponge Bob likes watermelon. When you see watermelon press a smiley face on this box’. ‘Sponge Bob does not like oranges. When you see an orange, press an unhappy face on this box’. Before the task commenced, the experimenter explained the rules using A4 cards showing the correct pairings and asked the children to repeat the instructions and show which buttons to press. After receiving instructions, the children completed 12 practice trials. Children made responses using a response box, where two buttons were marked with stickers: a yellow happy face to indicate ‘like’ responses and a red unhappy face to indicate ‘dislike’ responses. The blocks of task trials were interspersed with periods of rest lasting 2 min, during which children watched a cartoon.Each of the three blocks of trials was signalled with a presentation of an auditory cue lasting 3000 ms. This was followed by an on‐screen reminder of the rules displayed for 6000 ms (2 screens – each displayed for 3000 ms). Each trial started with a presentation of the cue for 500 ms and after a blank screen delay of 1200 ms, a probe was shown for a maximum of 5000 ms. After each response, a child was given verbal feedback: ‘Well done’ for correct responses, ‘Don't forget the rules’ for incorrect responses and ‘Too slow. Try to press the button faster next time’ – for missed responses. A schematic presentation of the AX‐CPT task structure is shown in Figure AX) – Z(FBX). For the d‐prime index of reactive control, a false alarm rate on AY trials was used: Z(HAX) – Z(FAY). To adjust for trials where zeros were present, a constant of 0.5 was added to all data cells  and showed similar patterns of correlation with ADHD and conduct problems. Therefore, the mean of proactive and reactive indices was calculated to transform these into a single index of inhibitory control.Proactive and reactive d‐prime indices were calculated from the normalized hit rate on AX trials  and false alarm rate on BX trials : Z and point biserial  correlation coefficients were calculated for the associations between inhibitory control, negative affect, surgency, effortful control, ADHD symptoms and conduct problems, age and sex. Partial correlations controlling for conduct problems were also calculated. Path analysis based on 5000 bootstrap samples was conducted using R Rosseel, . We did Rosseel, , who useOnly variables that were significantly correlated with ADHD symptoms or inhibitory control were included in the next step of the analysis (path model), given the modest size of the sample. Therefore, negative affect and surgency were not included in further analysis. Direct and indirect paths were modelled from ADHD symptoms to inhibitory control via effortful control, and vice versa, using age and conduct problems as the covariates. Given the cross‐sectional nature of the data, the choice of predictor and outcome was arbitrary, and we expected the models with ADHD symptoms, and those with inhibitory control as the predictor and the outcome, respectively, to be roughly equivalent. We reported the model with ADHD symptoms as the predictor in the main body of the paper (Model 1) and the equivalent model with inhibitory control as the predictor in Appendix SD = 17.5). For trials requiring rare non‐target response, accuracy on AY trials was 65.1% (SD = 29.4), on BX trials was 52.9% (SD = 31.1) and on BY trials was 62.6% (SD = 25.2).On average, children completed 88 trials of the AX‐CPT. Responses made within 200 ms of probe presentation were treated as anticipatory  and a mean d‐prime index of reactive inhibition was 2.24 (SD = 1.28). Correlations between both d‐prime indices, ADHD symptoms and conduct problems are shown in Table A mean d‐prime index of proactive inhibition was 1.85 SD = 1.6 and a mSD) and correlations between age, sex, index of inhibitory control, temperament variables and ADHD symptoms and partial correlations controlling for conduct problems are shown in Table The means, standard deviations . After controlling for conduct problems, only the association with effortful control remained significant . Inhibitory control was significantly positively correlated with effortful control and age . These correlations remained significant after controlling for conduct problems. Surgency was positively correlated with male sex  and negatively with negative affect  and these associations remained significant after conduct problems were controlled for. No other correlations were significant . Given that neither negative affect nor surgency were significantly correlated with ADHD symptoms or inhibitory control, these were not included in the next analysis step.Symptoms of ADHD were significantly negatively correlated with effortful and inhibitory control (χ2(10) = 54.7, p < .001. In Model 1, there was a significant negative path from ADHD symptoms to effortful control . There was also a significant indirect path from ADHD symptoms to inhibitory control via reduced effortful control , but the path to effortful control was not significant . Finally, inhibitory control was also positively associated with effortful control  and with age .Both path models achieved a very good fit, CFI = 1.0, RMSEA = .00, In this cross‐sectional study of children recruited from the community, we examined the relationship between ADHD symptoms, inhibitory control deficits and effortful control. We tested the specific hypothesis that the association between ADHD symptoms and inhibitory control deficits is grounded in temperamental variations in effortful control. To explore the specificity of these relationships we also examined two other temperament factors, namely, negative affect and surgency, while also controlling for conduct problems.The results of bivariate correlations and path analysis showed that ADHD symptoms and conduct problems were associated with deficits in inhibitory control measured by the AX‐CPT task. This is consistent with the previous meta‐analytical results, which showed that inhibitory deficits are not a unique characteristic of a particular disorder, for example, ADHD, but are found across many childhood and adult psychopathologies . Although this reduction does not appear substantial in size, the correlation was no longer statistically significant. This finding contrasts with the results of Krieger et al. (First, when conduct problems were controlled for, the bivariate correlation between symptoms of ADHD and inhibitory performance reduced in effect size (r et al. , which sSecond, the exploratory path analysis showed that the associations between ADHD symptoms, conduct problems and poor inhibitory task performance were unique to the type of psychopathology. Low effortful control fully explained the association between ADHD symptoms and poor inhibitory task performance. This finding fits with the cognitive‐energetic model first proposed by Sanders  and subsindirect association seen in relation to the inhibitory control deficits and ADHD symptoms, exploratory analysis of the associations between conduct problems and inhibitory control showed a direct negative link between these variables. This fits with the overall pattern of previous findings showing the associations between inhibitory deficits in early childhood and general externalizing difficulties (Schoemaker et al., In contrast to the In addition to the above findings, our data showed that proactive and reactive inhibitory control were best modelled as a single construct. They were both highly correlated with each other and showed similar patterns of correlation with ADHD symptoms and conduct problems. This contrasts with the evidence for the two modes of inhibitory control, which are dissociable in early childhood. Prior research with children aged 8 years and younger provided evidence for a developmental shift from reactive inhibition to proactive inhibition (Chatham et al., The evidence of the shift from automatic, stimulus‐driven to purposeful and goal‐driven behaviour fits with the generally accepted dual‐process approach, which characterizes much of the cognitive and developmental theory and research. However, this approach has been criticized for its lack of ability to account for the complexity and dynamic nature of human behaviour, which is likely to be underpinned by a combination of automatic and goal‐directed processes (Hommel & Wiers, An important contribution of this study is that it brings together temperamental and child psychopathology symptoms to examine their contribution to inhibitory performance. Moreover, it differentiates between the nature of inhibitory deficits in ADHD symptoms and conduct problems – as revealed in their associations with effortful control. However, findings should be considered in the context of three limitations. First, while the cross‐sectional design of the study allowed us to take the first step in examining the potential role of temperament in the ADHD‐inhibitory control deficit links, we were unable to establish the developmental sequence or whether the observed associations persisted over time. One hypothesis that can be tested with longitudinal data, including that collected during the early pre‐school period, is whether alterations in primary inhibitory control deficits specifically and executive functions more generally represent an early neurodevelopmental pre‐cursor of the later development of ADHD that may be linked to temperamental differences in effortful control (Sonuga‐Barke & Halperin, In conclusion, this study provides evidence that the association between ADHD symptoms and inhibitory control problems was statistically mediated by low effortful control while conduct problems were directly linked to poor inhibitory performance. Further, there was no evidence that ADHD symptoms in a community sample of children were linked to increased negative affect and higher levels of surgency. It is important for future research to include children with a wider range of ADHD‐ and conduct problem‐related difficulties, including clinically referred children.Katarzyna Kostyrka‐Allchorne: Formal analysis; project administration; supervision; writing – original draft. Sam V. Wass: Conceptualization; supervision; writing – review and editing. Hodo Yusuf: Investigation; writing – review and editing. Vidya Rao: Data curation; writing – review and editing. Chloe Bertini: Investigation; writing – review and editing. Edmund J. S. Sonuga‐Barke: Conceptualization; methodology; supervision; writing – review and editing.All authors declare no conflict of interest.Appendix S1Click here for additional data file.