Clinical utility of point-of-care glucose testing in the assessment of gestational diabetes: Prospective cohort study.

OBJECTIVE: To assess the clinical utility of point-of-care (POC) capillary blood glucose (CBG) testing in the assessment of gestational diabetes mellitus (GDM) during oral glucose tolerance test (OGTT). DESIGN: Prospective cohort study. SETTING: Antenatal clinics at King's College Hospital. POPULATION: Women screened for GDM between March and June 2020. METHODS: The CBG was measured using the POC StatStrip® test and the venous plasma glucose (VPG) was measured by Roche analyser (Cobas 8000 c702). GDM was diagnosed based on the 2015 National Institute for Health and Clinical Excellence (NICE) Clinical Guideline criteria. The two methods were compared statistically using Analyse-It 5.40.2. MAIN OUTCOME MEASURES: Diagnostic sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the POC StatStrip® test, compared with VPG measured by reference laboratory method. RESULTS: A total of 230 women were included. The number and percentage of women with glucose concentrations above the GDM threshold using the POC StatStrip® test versus laboratory VPG measurement was 15 (6.5%) versus eight (3.4%) at fasting and 105 (45.6%) versus 72 (31.1%) at 2 h, respectively. The sensitivity and specificity values (and 95% CIs) for the POC StatStrip® test were 88% (52%-99%) and 97% (93%-98%) at fasting and 97% (91%-99%) and 79% (71%-84%) at 2 h, respectively. However, the specificity and the NPV for the POC StatStrip® test for concentrations of ≤5.0 mmol/L at fasting or <7.5 mmol/L at 2 h were 100%, and the sensitivity and the PPV for concentrations of >9.5 mmol/L at 2 h were 100%. CONCLUSIONS: In our cohort the POC measurement of CBG cannot entirely replace the laboratory method for the OGTT; however, it can be used to rule out/rule in GDM for glucose concentrations of ≤5.0 mmol/L at fasting or <7.5/>9.5 mmol/L at 2 h.

Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes.

BACKGROUND: Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear. METHODS: In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks' gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events. RESULTS: A total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, -10.2 percentage points; 95% CI, -13.8 to -6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, -0.31 percentage points; 95% CI, -0.50 to -0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy). CONCLUSIONS: Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.).

Cross-disciplinary CURE Program Increases Educational Aspirations in a Large Community College.

Undergraduate research experiences have been widely demonstrated as a beneficial and essential component of the college experience. However, many community colleges face barriers and lack of support in implementing such research programs, which means a significant number of community college students miss out on these impactful experiences. Course-based undergraduate research experiences (CUREs) represent a feasible way to increase access to research experiences within community colleges. To investigate whether these CURE opportunities resulted in comparable to 4-year university CURE students, a CURE program was developed across various disciplines in a large community college and the impact on community college students was assessed. Analysis of both qualitative and quantitative data showed that students reported improvement in research skills, increases in confidence, and increases in educational aspirations. Peer interactions and instructor relationships in CUREs were identified as key factors associated with increases in research skills. Key factors associated with increases in educational aspirations included confidence in research-based courses, seeking additional research opportunities, and building a meaningful relationship with the instructor, but only if confidence increased as well. Our findings indicate that CUREs positively impact student outcomes in the community college setting and may provide increased access to research experiences.

Nonadiabatic transition probabilities for quantum systems in electromagnetic fields: Dephasing and population relaxation due to contact with a bath.

We contrast Dirac's theory of transition probabilities and the theory of nonadiabatic transition probabilities, applied to a perturbed system that is coupled to a bath. In Dirac's analysis, the presence of an excited state |k0⟩ in the time-dependent wave function constitutes a transition. In the nonadiabatic theory, a transition occurs when the wave function develops a term that is not adiabatically connected to the initial state. Landau and Lifshitz separated Dirac's excited-state coefficients into a term that follows the adiabatic theorem of Born and Fock and a nonadiabatic term that represents excitation across an energy gap. If the system remains coherent, the two approaches are equivalent. However, differences between the two approaches arise when coupling to a bath causes dephasing, a situation that was not treated by Dirac. For two-level model systems in static electric fields, we add relaxation terms to the Liouville equation for the time derivative of the density matrix. We contrast the results obtained from the two theories. In the analysis based on Dirac's transition probabilities, the steady state of the system is not an equilibrium state; also, the steady-state population ρkk,s increases with increasing strength of the perturbation and its value depends on the dephasing time T2. In the nonadiabatic theory, the system evolves to the thermal equilibrium with the bath. The difference is not simply due to the choice of basis because the difference remains when the results are transformed to a common basis.

Onset of an Active Charcot Foot in a Person with Longstanding Type 1 Diabetes and Normal Vibration Perception Threshold-A Case Report.

Charcot neuro-osteoarthropathy (CNO), or Charcot foot, is a disabling complication of diabetes, which is poorly understood and frequently overlooked. We describe an atypical presentation of an active Charcot foot in a woman with a long-standing type 1 diabetes who did not exhibit loss of protective sensation (sensate to a 10-gram monofilament) or loss of vibration sensation. These standard measures of large nerve fibre function ruled out "classical" neuropathy. However, additional testing showed reduced sweat gland function most likely related to degeneration of c-fibres (small fibre neuropathy). This case raises the awareness that in addition to the "textbook" description, in diabetes, Charcot foot can develop in individuals with "minimal" or "no signs" of clinical neuropathy. The onset of active Charcot foot should be suspected in every person with diabetes and history of trauma even when foot and ankle x-rays are normal. Offloading should be initiated until the diagnosis is proven otherwise.

Rollout of Closed-Loop Technology to Pregnant Women with Type 1 Diabetes: Healthcare Professionals' Views About Potential Challenges and Solutions.

Aims: To explore healthcare professionals' views about the training and support needed to rollout closed-loop technology to pregnant women with type 1 diabetes. Methods: We interviewed (n = 19) healthcare professionals who supported pregnant women using CamAPS FX closed-loop during the Automated insulin Delivery Amongst Pregnant women with Type 1 diabetes (AiDAPT) trial. Data were analyzed descriptively. An online workshop involving (n = 15) trial team members was used to inform recommendations. Ethics approvals were obtained in conjunction with those for the wider trial. Results: Interviewees expressed enthusiasm for a national rollout of closed-loop, but anticipated various challenges, some specific to use during pregnancy. These included variations in insulin pump and continuous glucose monitoring expertise and difficulties embedding and retaining key skills, due to the relatively small numbers of pregnant women using closed-loop. Inexperienced staff also highlighted difficulties interpreting data downloads. To support rollout, interviewees recommended providing expert initial advice training, delivered by device manufacturers together with online training resources and specific checklists for different systems. They also highlighted a need for 24 h technical support, especially when supporting technology naive women after first transitioning onto closed-loop in early pregnancy. They further recommended providing case-based meetings and mentorship for inexperienced colleagues, including support interpreting data downloads. Interviewees were optimistic that if healthcare professionals received training and support, their long-term workloads could be reduced because closed-loop lessened women's need for glycemic management input, especially in later pregnancy. Conclusions: Interviewees identified challenges and opportunities to rolling-out closed-loop and provided practical suggestions to upskill inexperienced staff supporting pregnant women using closed-loop. A key priority will be to determine how best to develop mentorship services to support inexperienced staff delivering closed-loop. Clinical Trials Registration: NCT04938557.

The gestational diabetes future diabetes prevention study (GODDESS): A partially randomised feasibility controlled trial.

OBJECTIVES: To assess the feasibility of an ante- and post-natal lifestyle intervention for women with gestational diabetes mellitus (GDM) to reduce type 2 diabetes risk. DESIGN: A partially randomised patient preference feasibility trial. SETTING: Diabetes antenatal clinics in two inner-London hospitals, UK. PARTICIPANTS: Pregnant women ≥18 years with a GDM diagnosis and pre-pregnancy body mass index of ≥25kg/m2. INTERVENTION: Participants in the intervention group were offered four motivational interview-based sessions (two antenatally and two postnatally, at 3 and 6 months postpartum), a WhatsApp support group, a FitBit and electronic self-help resources. OUTCOME MEASURES: Recruitment; retention; intervention dose received; data completion; adaptions; proportion achieving ≥5% weight loss; weight change, blood glucose; blood pressure; diet, physical activity, breastfeeding and depression. Clinical outcomes were measured at baseline and 6 months postpartum. RESULTS: 50 participants were recruited from 155 eligible women (32% recruitment rate). Thirty-four were recruited to the intervention group (23 following randomisation (RI-group) and 11 based on preference (PI-group)); and 16 to the control group (13 randomised (RC-group) and 3 preference (PC-group)). Attrition was 44% (n = 22/50). Forty-six percent (n = 6) of the intervention group (25% (n = 2) of the RI-group and 80% (n = 4) of the PI-group) achieved ≥5% weight loss compared to 8% (n = 1) in the control group (95% confidence interval (CI) -0.69 to 0.07). Mean weight change was -2.1kg±9.0 in the intervention group (0kg±5.4 in the RI-group and -5.4kg±13.0 in the PI-group) compared to +4.4kg±4.9 in the control group (RC +4.4kg ±5.3 and PC +4.7kg ±3.1, 95% CI -12.4 to 0.2). CONCLUSIONS: Recruitment was feasible, but strategies to improve retention are needed. The findings suggest the intervention can support women with GDM to lose weight. The observed weight loss was primarily in women who preferred the intervention. Therefore, future trials may need to adopt a preference design and consider factors associated with preference. TRIAL REGISTRATION: Trial registration: ISRCTN52675820 https://www.isrctn.com/ISRCTN52675820?q=ISRCTN52675820&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search.

AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial - study protocol.

BACKGROUND: Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications. Despite using diabetes technologies including continuous glucose monitoring (CGM), insulin pumps and contemporary insulin analogues, most women struggle to achieve and maintain the recommended pregnancy glucose targets. This study aims to evaluate whether the use of automated closed-loop insulin delivery improves antenatal glucose levels in pregnant women with type 1 diabetes. METHODS/DESIGN: A multicentre, open label, randomized, controlled trial of pregnant women with type 1 diabetes and a HbA1c of ≥48 mmol/mol (6.5%) at pregnancy confirmation and ≤ 86 mmol/mol (10%) at randomization. Participants who provide written informed consent before 13 weeks 6 days gestation will be entered into a run-in phase to collect 96 h (24 h overnight) of CGM glucose values. Eligible participants will be randomized on a 1:1 basis to CGM (Dexcom G6) with usual insulin delivery (control) or closed-loop (intervention). The closed-loop system includes a model predictive control algorithm (CamAPS FX application), hosted on an android smartphone that communicates wirelessly with the insulin pump (Dana Diabecare RS) and CGM transmitter. Research visits and device training will be provided virtually or face-to-face in conjunction with 4-weekly antenatal clinic visits where possible. Randomization will stratify for clinic site. One hundred twenty-four participants will be recruited. This takes into account 10% attrition and 10% who experience miscarriage or pregnancy loss. Analyses will be performed according to intention to treat. The primary analysis will evaluate the change in the time spent in the target glucose range (3.5-7.8 mmol/l) between the intervention and control group from 16 weeks gestation until delivery. Secondary outcomes include overnight time in target, time above target (> 7.8 mmol/l), standard CGM metrics, HbA1c and psychosocial functioning and health economic measures. Safety outcomes include the number and severity of ketoacidosis, severe hypoglycaemia and adverse device events. DISCUSSION: This will be the largest randomized controlled trial to evaluate the impact of closed-loop insulin delivery during type 1 diabetes pregnancy. TRIAL REGISTRATION: ISRCTN 56898625 Registration Date: 10 April, 2018.

An integrated primary care-based programme of PRE-Pregnancy cARE to improve pregnancy outcomes in women with type 2 Diabetes (The PREPARED study): protocol for a multi-method study of implementation, system adaptation and performance.

BACKGROUND: The number of women of childbearing age with Type 2 diabetes(T2DM) is increasing, and they now account for > 50% of pregnancies in women with pre-existing diabetes. Diabetes pregnancies without adequate pre-pregnancy care have higher risk for poor outcomes (miscarriages, birth-defects, stillbirths) and are associated with increased complications (caesarean deliveries, macrosomic babies, neonatal intensive-care admissions). The risks and costs of these pregnancies can be reduced with pregnancy preparation (HbA1c, ≤ 6.5%, 5 mg folic acid and stopping potentially harmful medicines). However, 90% of women with T2DM, most of whom are based in primary care, are not adequately prepared for pregnancy. This study will evaluate a programme of primary care-based interventions (decision-support systems; pre-pregnancy care-pathways; pregnancy-awareness resources; professional training; and performance monitoring) to improve pregnancy preparation in women with T2DM. METHODS: The study aims to optimise the programme interventions and estimate their impact on pregnancy preparation, pre-pregnancy care uptake and pregnancy outcomes. To evaluate this multimodal intervention, we will use a multi-method research design following Complex Adaptive Systems (CAS) theory, refining the interventions iteratively during the study. Thirty GP practices with ≥ 25 women with T2DM of reproductive age (18-45 years) from two South London boroughs will be exposed to the intervention. This will provide > 750 women with an estimated pregnancy incidence of 80-100 to study. The research involves: a clinical audit of processes and outcomes; a process evaluation informing intervention feasibility, implementation, and behaviour change; and a cost-consequences analysis informing future economic evaluation. Performance data will be collected via audits of GP systems, hospital antenatal clinics and pregnancy outcomes. Following CAS theory, we will use repeated measurements to monitor intervention impact on pregnancy preparation markers at 4-monthly intervals over 18-months. We will use performance and feasibility data to optimise intervention effects iteratively. The target performance for the intervention is a 30% increase in the proportion of women meeting pre-pregnancy care criteria. DISCUSSION: The primary output will be development of an integrated programme of interventions to improve pregnancy preparation, pre-pregnancy care uptake, and reduce adverse pregnancy outcomes in women with T2DM. We will also develop an implementation plan to support the introduction of the interventions across the NHS. TRIAL REGISTRATION: ISRCTN47576591 ; February 8, 2022.

Shannon and von Neumann entropies of multi-qubit Schrödinger's cat states.

Using IBM's publicly accessible quantum computers, we have analyzed the entropies of Schrödinger's cat states, which have the form Ψ = (1/2)1/2 [|0 0 0⋯0〉 + |1 1 1⋯1〉]. We have obtained the average Shannon entropy SSo of the distribution over measurement outcomes from 75 runs of 8192 shots, for each of the numbers of entangled qubits, on each of the quantum computers tested. For the distribution over N fault-free measurements on pure cat states, SSo would approach one as N → ∞, independent of the number of qubits; but we have found that SSo varies nearly linearly with the number of qubits n. The slope of SSoversus the number of qubits differs among computers with the same quantum volumes. We have developed a two-parameter model that reproduces the near-linear dependence of the entropy on the number of qubits, based on the probabilities of observing the output 0 when a qubit is set to |0〉 and 1 when it is set to |1〉. The slope increases as the error rate increases. The slope provides a sensitive measure of the accuracy of a quantum computer, so it serves as a quickly determinable index of performance. We have used tomographic methods with error mitigation as described in the qiskit documentation to find the density matrix ρ and evaluate the von Neumann entropies of the cat states. From the reduced density matrices for individual qubits, we have calculated the entanglement entropies. The reduced density matrices represent mixed states with approximately 50/50 probabilities for states |0〉 and |1〉. The entanglement entropies are very close to one.

Sulfated Progesterone Metabolites That Enhance Insulin Secretion via TRPM3 Are Reduced in Serum From Women With Gestational Diabetes Mellitus.

Serum progesterone sulfates were evaluated in the etiology of gestational diabetes mellitus (GDM). Serum progesterone sulfates were measured using ultra-performance liquid chromatography-tandem mass spectrometry in four patient cohorts: 1) the Hyperglycemia and Adverse Pregnancy Outcomes study; 2) London-based women of mixed ancestry and 3) U.K.-based women of European ancestry with or without GDM; and 4) 11-13 weeks pregnant women with BMI ≤25 or BMI ≥35 kg/m2 with subsequent uncomplicated pregnancies or GDM. Glucose-stimulated insulin secretion (GSIS) was evaluated in response to progesterone sulfates in mouse islets and human islets. Calcium fluorescence was measured in HEK293 cells expressing transient receptor potential cation channel subfamily M member 3 (TRPM3). Computer modeling using Molecular Operating Environment generated three-dimensional structures of TRPM3. Epiallopregnanolone sulfate (PM5S) concentrations were reduced in GDM (P < 0.05), in women with higher fasting plasma glucose (P < 0.010), and in early pregnancy samples from women who subsequently developed GDM with BMI ≥35 kg/m2 (P < 0.05). In islets, 50 µmol/L PM5S increased GSIS by at least twofold (P < 0.001); isosakuranetin (TRPM3 inhibitor) abolished this effect. PM5S increased calcium influx in TRPM3-expressing HEK293 cells. Computer modeling and docking showed identical positioning of PM5S to the natural ligand in TRPM3. PM5S increases GSIS and is reduced in GDM serum. The activation of GSIS by PM5S is mediated by TRPM3 in both mouse and human islets.

An integrated pre-pregnancy care programme framework theoretically modelled from the perspectives of women with Type 2 diabetes and healthcare professionals.

BACKGROUND: Pregnancies in women with diabetes are associated with significant additional risks for the fetus, infant and mother such as, higher risk of stillbirths or congenital anomalies. Pre-pregnancy care can attenuate these risks. However, while women with Type 2 diabetes account for half of pregnancies in women with pre-existing diabetes, they are much less likely to receive pre-pregnancy care than women with Type 1 diabetes. This discrepancy may be related to the fact that most pre-pregnancy care is located in specialist diabetes centres where women with Type 1 diabetes are managed; whereas women with Type 2 diabetes are managed in primary care and reproductive care is not a routine element of diabetes care. Therefore, to improve pre-pregnancy care among women with Type 2 diabetes strategies need to be tailored to the specific needs of this group and the context of their diabetes care. OBJECTIVES: This paper seeks to inform the development of an integrated pre-pregnancy care programme by presenting strategies identified by women with Type 2 diabetes and healthcare professionals that address some of the barriers they experience in relation to pre-pregnancy care. METHODS: A qualitative study using semi-structured in-depth interviews with women of reproductive age with Type 2 diabetes (n=30) and diabetes healthcare professionals (n=22) from both primary and secondary care. Data were transcribed verbatim and analysed thematically using Framework Analysis. The identified themes were then mapped to create a theoretical intervention framework using Normalisation Process Theory and the Capabilities, Opportunity, and Motivation to perform a Behaviour model. RESULTS: Six themes were identified expressing the need for a multimodal approach for improving the uptake of pre-pregnancy care in women with Type 2 diabetes. These themes were then mapped onto the constructs of Normalisation Process Theory as follows: coherence (enhancing understanding of reproductive needs among women and healthcare professionals); cognitive participation (constructing a positive narrative for pregnancy and Type 2 diabetes); collective action (increasing the visibly of the reproductive needs of women, integrating healthcare systems and utilising supportive technologies); and reflexive monitoring (using multi-modal approaches to support systemised care). The data were also modelled to identify target behaviours for intervention detailing what needs to be done by whom, when and where. CONCLUSION: Women with Type 2 diabetes account for half of pregnancies in those with pre-existing diabetes; however, they are less likely to receive pre-pregnancy care than women with Type 1 diabetes. Pre-pregnancy care can reduce the maternal and fetal risks associated with Type 2 diabetes. This study presents strategies to improve the current low uptake of pre-pregnancy care for women with Type 2 diabetes. These strategies have been tailored to the specific needs of women and healthcare professionals and support integration within the woman's routine diabetes management.

Bell inequalities for entangled qubits: quantitative tests of quantum character and nonlocality on quantum computers.

This work provides quantitative tests of the extent of violation of two inequalities applicable to qubits coupled into Bell states, using IBM's publicly accessible quantum computers. Violations of the inequalities are well established. Our purpose is not to test the inequalities, but rather to determine how well quantum mechanical predictions can be reproduced on quantum computers, given their current fault rates. We present results for the spin projections of two entangled qubits, along three axes A, B, and C, with a fixed angle θ between A and B and a range of angles θ' between B and C. For any classical object that can be characterized by three observables with two possible values, inequalities govern relationships among the probabilities of outcomes for the observables, taken pairwise. From set theory, these inequalities must be satisfied by all such classical objects; but quantum systems may violate the inequalities. We have detected clear-cut violations of one inequality in runs on IBM's publicly accessible quantum computers. The Clauser-Horne-Shimony-Holt (CHSH) inequality governs a linear combination S of expectation values of products of spin projections, taken pairwise. Finding S > 2 rules out local, hidden variable theories for entangled quantum systems. We obtained values of S greater than 2 in our runs prior to error mitigation. To reduce the quantitative errors, we used a modification of the error-mitigation procedure in the IBM documentation. We prepared a pair of qubits in the state |00〉, found the probabilities to observe the states |00〉, |01〉, |10〉, and |11〉 in multiple runs, and used that information to construct the first column of an error matrix M. We repeated this procedure for states prepared as |01〉, |10〉, and |11〉 to construct the full matrix M, whose inverse is the filtering matrix. After applying filtering matrices to our averaged outcomes, we have found good quantitative agreement between the quantum computer output and the quantum mechanical predictions for the extent of violation of both inequalities as functions of θ'.

Quantum transition probabilities due to overlapping electromagnetic pulses: Persistent differences between Dirac's form and nonadiabatic perturbation theory.

The probability of transition to an excited state of a quantum system in a time-dependent electromagnetic field determines the energy uptake from the field. The standard expression for the transition probability has been given by Dirac. Landau and Lifshitz suggested, instead, that the adiabatic effects of a perturbation should be excluded from the transition probability, leaving an expression in terms of the nonadiabatic response. In our previous work, we have found that these two approaches yield different results while a perturbing field is acting on the system. Here, we prove, for the first time, that differences between the two approaches may persist after the perturbing fields have been completely turned off. We have designed a pair of overlapping pulses in order to establish the possibility of lasting differences, in a case with dephasing. Our work goes beyond the analysis presented by Landau and Lifshitz, since they considered only linear response and required that a constant perturbation must remain as t → ∞. First, a "plateau" pulse populates an excited rotational state and produces coherences between the ground and excited states. Then, an infrared pulse acts while the electric field of the first pulse is constant, but after dephasing has occurred. The nonadiabatic perturbation theory permits dephasing, but dephasing of the perturbed part of the wave function cannot occur within Dirac's method. When the frequencies in both pulses are on resonance, the lasting differences in the calculated transition probabilities may exceed 35%. The predicted differences are larger for off-resonant perturbations.

Repurposing a Neurocritical Care Unit for the Management of Severely Ill Patients With COVID-19: A Retrospective Evaluation.

BACKGROUND: The World Health Organisation declared a coronavirus disease 2019 (COVID-19) pandemic on March 11, 2020. Following activation of the UK pandemic response, our institution began planning for admission of COVID-19 patients to the neurointensive care unit (neuro-ICU) to support the local critical care network which risked being rapidly overwhelmed by the high number of cases. This report will detail our experience of repurposing a neuro-ICU for the management of severely ill patients with COVID-19 while retaining capacity for urgent neurosurgical and neurology admissions. METHODS: We conducted a retrospective process analysis of the repurposing of a quaternary level neuro-ICU during the early stages of the COVID-19 pandemic in the United Kingdom. We retrieved demographic data, diagnosis, and outcomes from the electronic health care records of all patients admitted to the ICU between March 1, 2020 and April 30, 2020. Processes for increase in surge capacity, reduction in ICU demand, and staff redeployment and rapid training are reported. RESULTS: Over a 10-day period, total ICU capacity was increased by 21.7% (from 23 to 28 beds) while the capacity to provide mechanical ventilation was increased by 77% (from 13 to 23 beds). There were 30 ICU admissions of 29 COVID-19 patients between March 1 and April 30, 2020; median (range) length of ICU stay was 9.9 (1.3 to 32) days, duration of mechanical ventilation 11 (1 to 27) days, and ICU mortality rate 41.4%. There was a 44% reduction in urgent neurosurgical and neurology admissions compared with the same period in 2019. CONCLUSIONS: It is possible to repurpose a dedicated neuro-ICU for the management of critically ill non-neurological patients during a pandemic response, while maintaining access for urgent neuroscience referrals.

Variance of the energy of a quantum system in a time-dependent perturbation: Determination by nonadiabatic transition probabilities.

For a quantum system in a time-dependent perturbation, we prove that the variance in the energy depends entirely on the nonadiabatic transition probability amplitudes bk(t). Landau and Lifshitz introduced the nonadiabatic coefficients for the excited states of a perturbed quantum system by integrating by parts in Dirac's expressions for the coefficients ck (1)(t) of the excited states to first order in the perturbation. This separates ck (1)(t) for each state into an adiabatic term ak (1)(t) and a nonadiabatic term bk (1)(t). The adiabatic term follows the adiabatic theorem of Born and Fock; it reflects the adjustment of the initial state to the perturbation without transitions. If the response to a time-dependent perturbation is entirely adiabatic, the variance in the energy is zero. The nonadiabatic term bk (1)(t) represents actual excitations away from the initial state. As a key result of the current work, we derive the variance in the energy of the quantum system and all of the higher moments of the energy distribution using the values of |bk(t)|2 for each of the excited states along with the energy differences between the excited states and the ground state. We prove that the same variance (through second order) is obtained in terms of Dirac's excited-state coefficients ck(t). We show that the results from a standard statistical analysis of the variance are consistent with the quantum results if the probability of excitation Pk is set equal to |bk(t)|2, but not if the probability of excitation is set equal to |ck(t)|2. We illustrate the differences between the variances calculated with the two different forms of Pk for vibration-rotation transitions of HCl in the gas phase.

A role for placental kisspeptin in ß cell adaptation to pregnancy.

During pregnancy the maternal pancreatic islets of Langerhans undergo adaptive changes to compensate for gestational insulin resistance. Kisspeptin has been shown to stimulate insulin release, through its receptor, GPR54. The placenta releases high levels of kisspeptin into the maternal circulation, suggesting a role in modulating the islet adaptation to pregnancy. In the present study we show that pharmacological blockade of endogenous kisspeptin in pregnant mice resulted in impaired glucose homeostasis. This glucose intolerance was due to a reduced insulin response to glucose as opposed to any effect on insulin sensitivity. A ß cell-specific GPR54-knockdown mouse line was found to exhibit glucose intolerance during pregnancy, with no phenotype observed outside of pregnancy. Furthermore, in pregnant women circulating kisspeptin levels significantly correlated with insulin responses to oral glucose challenge and were significantly lower in women with gestational diabetes (GDM) compared with those without GDM. Thus, kisspeptin represents a placental signal that plays a physiological role in the islet adaptation to pregnancy, maintaining maternal glucose homeostasis by acting through the ß cell GPR54 receptor. Our data suggest reduced placental kisspeptin production, with consequent impaired kisspeptin-dependent ß cell compensation, may be a factor in the development of GDM in humans.

The interaction-induced dipole of H2-H: New ab initio results and spherical tensor analysis.

We present numerical results for the dipole induced by interactions between a hydrogen molecule and a hydrogen atom, obtained from finite-field calculations in an aug-cc-pV5Z basis at the unrestricted coupled-cluster level including all single and double excitations in the exponential operator applied to a restricted Hartree-Fock reference state, with the triple excitations treated perturbatively, i.e., UCCSD(T) level. The Cartesian components of the dipole have been computed for nine different bond lengths r of H2 ranging from 0.942 a.u. to 2.801 a.u., for 16 different separations R between the centers of mass of H2 and H between 3.0 a.u. and 10.0 a.u., and for 19 angles θ between the H2 bond vector r and the vector R from the H2 center of mass to the nucleus of the H atom, ranging from 0° to 90° in intervals of 5°. We have expanded the interaction-induced dipole as a series in the spherical harmonics of the orientation angles of the H2 bond axis and of the intermolecular vector, with coefficients DλL(r, R). For the geometrical configurations that we have studied in this work, the most important coefficients DλL(r, R) in the series expansion are D01(r, R), D21(r, R), D23(r, R), D43(r, R), and D45(r, R). We show that the ab initio results for D23(r, R) and D45(r, R) converge to the classical induction forms at large R. The convergence of D45(r, R) to the hexadecapolar induction form is demonstrated for the first time. Close agreement between the long-range ab initio values of D01(r0 = 1.449 a.u., R) and the known analytical values due to van der Waals dispersion and back induction is also demonstrated for the first time. At shorter range, D01(r, R) characterizes isotropic overlap and exchange effects, as well as dispersion. The coefficients D21(r, R) and D43(r, R) represent anisotropic overlap effects. Our results for the DλL(r, R) coefficients are useful for calculations of the line shapes for collision-induced absorption and collision-induced emission in the infrared and far-infrared by gas mixtures containing both H2 molecules and H atoms.

Adenosine-assisted neurovascular surgery: initial case series and review of literature.

Cerebral aneurysms in complex anatomical locations and intraoperative rupture of aneurysms are challenging for neurosurgeons and anaesthetists alike. Mechanical and non-mechanical methods to reduce blood flow into aneurysms are well-recognised techniques to facilitate aneurysm exclusion from the circulation. Mechanical methods like temporary clipping of parent arteries, carotid artery ligation and endovascular balloon occlusion are commonly used in clinical practice. However, non-mechanical techniques such as rapid ventricular pacing and adenosine-induced cardiac standstill with hypotension are still emerging strategies. The aim of this study is to report our units' experience in the use of adenosine in aneurysm clipping and arteriovenous malformation (AVM) resection and review the literature. The records of all patients who had adenosine-assisted clipping of intracranial aneurysms and AVM resections in our institute between November 2015 and December 2016 were extracted from prospectively maintained database. The following data were collected: patient demographics, comorbidities, size and location of the aneurysms or AVM, number of boluses and total dose of adenosine administered, duration of cardiac standstill and hypotension (systolic blood pressure < 60 mmHg), intraoperative and postoperative complications and outcome scores at discharge. Literature search on Embase and PubMed for the terms "adenosine and clipping", "adenosine and aneurysm" and "adenosine and AVM" was performed. Eight aneurysms and two AVMs were identified. While both AVMs were elective procedures, half of the aneurysm clippings were on urgent basis. We used adenosine safely with spontaneous return of rhythm in all cases. Temporary clips to the parent artery were applied for brief periods in 2 patients who had pre-adenosine intraoperative rupture. We did not observe any immediate or late adverse events related to administration of adenosine. From our literature review, a total of ten case series and four case reports were identified. There were no reports on the use of adenosine in AVM resection. Transient adenosine-induced asystole is a safe and effective technique in facilitating surgical treatment of complex aneurysms and AVMs. In addition, adenosine use reduces the need, duration, and associated complications of temporary clip applications to parent arteries.

Dependence of the multipole moments, static polarizabilities, and static hyperpolarizabilities of the hydrogen molecule on the H-H separation in the ground singlet state.

In this work, we provide values for the quadrupole moment Θ, the hexadecapole moment Φ, the dipole polarizability α, the quadrupole polarizability C, the dipole-octopole polarizability E, the second dipole hyperpolarizability γ, and the dipole-dipole-quadrupole hyperpolarizability B for the hydrogen molecule in the ground singlet state, evaluated by finite-field configuration interaction singles and doubles (CISD) and coupled-cluster singles and doubles (CCSD) methods for 26 different H-H separations r, ranging from 0.567 a.u. to 10.0 a.u. Results obtained with various large correlation-consistent basis sets are compared at the vibrationally averaged bond length r0 in the ground state. Results over the full range of r values are presented at the CISD/d-aug-cc-pV6Z level for all of the independent components of the property tensors. In general, our values agree well with previous ab initio results of high accuracy for the ranges of H-H distances that have been treated in common. To our knowledge, for H2 in the ground state, our results are the first to be reported in the literature for Φ for r > 7.0 a.u., γ and B for r > 6.0 a.u., and C and E for any H-H separation outside a narrow range around the potential minimum. Quantum Monte Carlo values of Θ have been given previously for H-H distances out to 10.0 a.u., but the statistical error is relatively large for r > 7.0 a.u. At the larger r values in this work, αxx and αzz show the expected functional forms, to leading order in r-1. As r increases further, Θ and Φ vanish, while α, γ, and the components of B converge to twice the isolated-atom values. Components of C and E diverge as r increases. Vibrationally averaged values of the properties are reported for all of the bound states (vibrational quantum numbers υ = 0-14) with rotational quantum numbers J = 0-3.