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Delirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients. This was a case-control study of hospitalised patients aged ≥65 years with delirium (with or without pre-existing cognitive impairment), who were compared to patients with dementia without delirium, and patients without cognitive impairment. Reference standard delirium assessment, which included a neuropsychological test battery, was based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A separate blinded assessor administered the DelApp arousal assessment (score 0-4) and attention task (0-6) yielding an overall score of 0 to 10 (lower scores indicate poorer performance). Analyses included receiver operating characteristic curves and sensitivity and specificity. Optimal cut-points for delirium detection were determined using Youden's index. A total of 187 patients were recruited, mean age 83.8 (range 67-98) years, 152 (81%) women; n = 61 with delirium; n = 61 with dementia without delirium; and n = 65 without cognitive impairment. Patients with delirium performed poorly on the DelApp (median score = 4/10; inter-quartile range 3.0, 5.5) compared to patients with dementia (9.0; 5.5, 10.0) and those without cognitive impairment (10.0; 10.0, 10.0). Area under the curve for detecting delirium was 0.89 (95% Confidence Interval 0.84, 0.94). At an optimal cut-point of ≤8, sensitivity was 91.7% (84.7%, 98.7%) and specificity 74.2% (66.5%, 81.9%) for discriminating delirium from the other groups. Specificity was 68.3% (56.6%, 80.1%) for discriminating delirium from dementia (cut-point ≤6). Patients with delirium (with or without pre-existing cognitive impairment) perform poorly on the DelApp compared to patients with dementia and those without cognitive impairment. A cut-point of ≤8/10 is suggested as having optimal sensitivity and specificity. The DelApp is a promising tool for assessment of attention deficits associated with delirium in older hospitalised adults, many of whom have prior cognitive impairment, and should be further validated in representative patient cohorts.

Background Delirium is a common and serious clinical syndrome which is often missed in routine clinical care. The core cognitive feature is inattention. We developed a novel bedside neuropsychological test for assessing inattention in delirium implemented on a smartphone platform (DelApp). We aim to evaluate the diagnostic performance of the DelApp in a representative cohort of older hospitalised patients. Methods This is a prospective study of older non-scheduled hospitalised patients (target n  = 500, age ≥ 65), recruited from elderly care and acute orthopaedic wards. Exclusion criteria are: non-English speakers; severe vision or hearing impairment; photosensitive epilepsy. A structured reference standard delirium assessment based on DSM-5 criteria will be used, which includes a cognitive test battery administered by a trained assessor (Orientation-Memory-Concentration Test, Abbreviated Mental Test-10, Delirium Rating Severity Scale-Revised-98, digit span, months and days backwards, Vigilance A’ test) and assessment of arousal (Observational Scale of Level of Arousal, Richmond Agitation Sedation Scale). Prior change in cognition will be documented using the Informant Questionnaire on Cognitive Decline in the Elderly. Patients will be categorized as delirium (with/without dementia), possible delirium, dementia, no cognitive impairment, or undetermined. A separate assessor (blinded to diagnosis and assessments) will administer the DelApp index test within 3 h of the reference standard assessment. The DelApp comprises assessment of arousal (score 0-4) and sustained attention (score 0-6), yielding a total score between 0 and 10 (higher score = better performance). Outcomes (length of stay, mortality and discharge location) will be collected at 12 weeks. We will evaluate a priori cutpoints derived from a previous case-control study. Measures of the accuracy of DelApp will include sensitivity, specificity, positive and negative predictive values, and area under the ROC curve. We plan repeat assessments on up to 4 occasions in a purposive subsample of 30 patients (15 delirium, 15 no delirium) to examine changes over time. Discussion This study evaluates the diagnostic test accuracy of a novel smartphone test for delirium in a representative cohort of older hospitalised patients, including those with dementia. DelApp has the potential to be a convenient, objective method of improving delirium assessment for older people in acute care. Trial registration Clinical trials.gov, NCT02590796 . Registered on 29 Oct 2015. Protocol version 5, dated 25 July 2016.

Key summary points Aim To investigate performance of the Months of the Year Backwards (MOTYB) test in older hospitalised patients with delirium, dementia, and no cognitive impairment. Findings Half of the patients with delirium (46%) could not engage with MOTYB compared to only 11% of patients with dementia without delirium. In patients able to give responses, those with delirium or dementia performed significantly worse than those without cognitive impairment. Message Our findings show the potential value of analysing response patterns, especially initial engagement, self-correction, and ability to continue to do the task in addition to considering exclusively the capacity to correctly recite the months until July, June or January. Purpose To investigate performance of the Months of the Year Backwards (MOTYB) test in older hospitalised patients with delirium, dementia, and no cognitive impairment. Methods Secondary analysis of data from a case–control study of 149 hospitalised patients aged ≥ 65 years with delirium [with or without dementia ( N  = 50)], dementia [without delirium ( N  = 46)], and no cognitive impairment ( N  = 53). Verbatim transcripts of MOTYB audio recordings were analysed to determine group differences in response patterns. Results In the total sample [median age 85y (IQR 80–88), 82% female], patients with delirium were more often unable to recite months backward to November (36/50 = 72%) than patients with dementia (21/46 = 46%; p  < 0.01) and both differed significantly from patients without cognitive impairment (2/53 = 4%; p ’s < 0.001). 121/149 (81%) of patients were able to engage with the test. Patients with delirium were more often unable to engage with MOTYB (23/50 = 46%; e.g., due to reduced arousal) than patients with dementia (5/46 = 11%; p  < 0.001); both groups differed significantly ( p ’s < 0.001) from patients without cognitive impairment (0/53 = 0%). There was no statistically significant difference between patients with delirium (2/27 = 7%) and patients with dementia (8/41 = 20%) in completing MOTYB to January, but performance in both groups differed ( p  < 0.001 and p  < 0.02, respectively) from patients without cognitive impairment (35/53 = 66%). Conclusion Delirium was associated with inability to engage with MOTYB and low rates of completion. In patients able to engage with the test, error-free completion rates were low in delirium and dementia. Recording of engagement and patterns of errors may add useful information to MOTYB scoring.

The work presented in this thesis describes the first experimental study of the exclusive (e,e’pn) reaction. The data were gathered as a proof of principle study using time-of-flight detectors in an electron scattering environment for the first time. The (e,e’pn) reaction is sensitive to nucleon-nucleon correlations, particularly tensor correlations, and is being used to study the role of these within the nucleus. Three target nuclei were studied, 2H, 3He, and 16O. The experiment was carried out using the MAMI-B electron microtron and the 3-spectrometer facility of the AI-collaboration at the Institut für Kernphysik, Mainz, Germany. The MAMI microtron provides a 100% c.w. beam of 855 MeV electrons which were used to induce the (e,e’pn) reaction. A magnetic spectrometer. Spectrometer B, was used to detect the scattered electrons for all three target nuclei and a large plastic scintillator hodoscope, HADRON3, was used to detect the protons for the 2H and 3He targets while for the 16O target another magnetic spectrometer. Spectrometer A, was used. A large time-of-flight scintillator array, TOF, was used for detection of the neutrons in all cases. Data were taken on the 2H target for calibration purposes and to provide a check on the cross section measurements. These data were taken at an energy transfer of 190 MeV and momentum transfer of 300 MeV/c. The 3He data were taken at an energy transfer of 220 MeV and momentum transfer of 375 MeV/c. The 16O data were taken at super-parallel kinematics with energy and momentum transfers of 215 MeV and 316 MeV/c respectively. The detector system for the 16O target has an energy resolution of 2 MeV allowing some separate states in the residual 14N nucleus to be identified. Analysis of data collected on the 2H target is compared to theoretical calculations of the 2H(e,e’p) reaction that are generally accepted as being a good description of the experimental data for the reaction. Good agreement between the theoretical and experimentally measured cross-sections in conjunction with a test of the method used to describe the neutron detection efficiency in the TOF array gives confidence that the experimental technique used is sound and that results for the other two target nuclei are reliable. The data analysed for the 3He target is compared to continuum Faddeev calculations describing the reaction and show good agreement on the whole. These calculations imply that short-range and tensor correlations provide the main reaction mechanism involved in the knockout of the proton-neutron pairs from 3He at the kinematics studied. The data collected on the 16O target have been analysed separately for each excited state identified in the residual 14N nucleus and compared to theoretical calculations describing the reaction. The experimentally determined cross-sections do not show good agreement with the theoretical predictions of the strength or shape of these cross-sections. The models indicate that the main contribution to the observed cross-sections is from two-body currents. Tensor correlations also play a significant role in the reaction whereas short range correlations are only marginal in the transitions to the observed states. The experimental technique has been shown to be viable in that the initial objective of observing a clear signal from the (e,e’pn) reaction has been achieved.

We present measurements of the polarization-transfer components in the \\(^2\\)H\\(( e,e' p)\\) reaction, covering a previously unexplored kinematic region with large positive (anti-parallel) missing momentum, \\(p_ miss\\), up to 220 MeV\\(/c\\), and \\(Q^2=0.65\\) \\(( GeV/c)^2\\). These measurements, performed at the Mainz Microtron (MAMI), were motivated by theoretical calculations which predict small final-state interaction (FSI) effects in these kinematics, making them favorable for searching for medium modifications of bound nucleons in nuclei. We find in this kinematic region that the measured polarization-transfer components \\(P_x\\) and \\(P_z\\) and their ratio agree with the theoretical calculations, which use free-proton form factors. Using this, we establish upper limits on possible medium effects that modify the bound proton's form factor ratio \\(G_E/G_M\\) at the level of a few percent. We also compare the measured polarization-transfer components and their ratio for \\(^2\\)H to those of a free (moving) proton. We find that the universal behavior of \\(^2\\)H, \\(^4\\)He and \\(^12\\)C in the double ratio \\((P_x/P_z)^A(P_x/P_z)^^1 H\\) is maintained in the positive missing-momentum region.

We present measurements of the electron helicity asymmetry in quasi-elastic proton knockout from \\(^2\\)H and \\(^12\\)C nuclei by polarized electrons. This asymmetry depends on the fifth structure function, is antisymmetric with respect to the scattering plane, and vanishes in the absence of final-state interactions, and thus it provides a sensitive tool for their study. Our kinematics cover the full range in off-coplanarity angle \\(_pq\\), with a polar angle \\(_pq\\) coverage up to about 8 degrees. The missing energy resolution enabled us to determine the asymmetries for knock-out resulting in different states of the residual \\(^11\\)B system. We find that the helicity asymmetry for \\(p\\)-shell knockout from \\(^12\\)C depends on the final state of the residual system and is relatively large (up to \\( 0.16\\)), especially at low missing momentum. It is considerably smaller (up to \\( 0.01\\)) for \\(s\\)-shell knockout from both \\(^12\\)C and \\(^2\\)H. The data for \\(^2\\)H are in very good agreement with theoretical calculations, while the predictions for \\(^12\\)C exhibit differences with respect to the data.

Differential cross sections for elastic scattering of photons from the deuteron have recently been measured at the Tagged-Photon Facility at the MAX IV Laboratory in Lund, Sweden. These first new measurements in more than a decade further constrain the isoscalar electromagnetic polarizabilities of the nucleon and provide the first-ever results above 100 MeV, where the sensitivity to the polarizabilities is increased. We add 23 points between 70 and 112 MeV, at angles 60deg, 120deg and 150deg. Analysis of these data using a Chiral Effective Field Theory indicates that the cross sections are both self-consistent and consistent with previous measurements. Extracted values of _s = [12.1 +/- 0.8(stat) +/- 0.2(BSR) +/- 0.8(th)] X 10^-4 fm^3 and _s = [2.4 +/- 0.8(stat) +/- 0.2(BSR) +/- 0.8(th)] X 10^-4 fm^3 are obtained from a fit to these 23 new data points. This paper presents in detail the experimental conditions and the data analysis used to extract the cross sections.

We report measurements of the induced polarization \\( P\\) of protons knocked out from \\(^2\\)H and \\(^12\\)C via the \\(A(e,e' p\\,)\\) reaction. We have studied the dependence of \\( P\\) on two kinematic variables: the missing momentum \\(p_ miss\\) and the \"off-coplanarity\" angle \\(_pq\\) between the scattering and reaction planes. For the full 360\\(\\) range in \\(_pq\\), both the normal (\\(P_y\\)) and, for the first time, the transverse (\\(P_x\\)) components of the induced polarization were measured with respect to the coordinate system associated with the scattering plane. \\(P_x\\) vanishes in coplanar kinematics, however in non-coplanar kinematics, it is on the same scale as \\(P_y\\). We find that the dependence on \\(_pq\\) is sine-like for \\(P_x\\) and cosine-like for \\(P_y\\). For carbon, the magnitude of the induced polarization is especially large when protons are knocked out from the \\(p_3/2\\) shell at very small \\(p_ miss\\). For the deuteron, the induced polarization is near zero at small \\(|p_ miss|\\), and its magnitude increases with \\(|p_ miss|\\). For both nuclei such behavior is reproduced qualitatively by theoretical results, driven largely by the spin-orbit part of the final-state interactions. However, for both nuclei, sizeable discrepancies exist between experiment and theory.

We report on a comprehensive reinterpretation of the existing cross-section data for elastic electron-proton scattering obtained by the initial-state radiation technique, resulting in a significantly improved accuracy of the extracted proton charge radius. By refining the external energy corrections we have achieved an outstanding description of the radiative tail, essential for a detailed investigation of the proton finite-size effects on the measured cross-sections. This development, together with a novel framework for determining the radius, based on a regression analysis of the cross-sections employing a polynomial model for the form factor, led us to a new value for the charge radius, which is \\((0.870 0.014_stat. 0.024_sys. 0.003_mod.)\\,fm\\).

In this multicenter, randomized, double-blind, placebo-controlled trial involving women with vaginal bleeding in early pregnancy, treatment with progesterone during the first trimester did not result in a significantly higher incidence of live births than placebo.