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Mothers’ preference for introducing and elaborating on mental states in conversations with their young children has been shown to be a significant predictor of children’s Theory of Mind development among Western samples. However, it is unclear whether this relationship still holds true in the Chinese cultural context. Exploratory in nature, the present study aims to study the relationship between mothers’ mental state talk and the development of Theory of Mind (ToM) in Chinese children (4-5 years old) following the framework of Peterson and Slaughter’s (2003) research. All participants (N = 94) were from middle-income families and were Chinese mothers of a 4-5-year-old typically developing children. Fifty-two pre-schoolers (M = 4.47 years, SD = .49) were boys. Adopting a correlational study design, the current study first looks at if there were individual differences in mothers’ conversational styles with their children. By running correlational analyses examining the relationships between different conversational styles, this assumption was confirmed. Given individual differences did exist, Pearson’s correlation was performed to decide if mothers’ preferences of language use significantly correlated with ToM development in Chinese children. The result from the correlation analysis indicated that no significant correlation emerged between mothers' self-reported preferences for sophisticated explanations of mental states and parental report of children's ToM. This null result was again confirmed by a hierarchical regression analysis showing that mothers’ conversational preferences were not predictors of Chinese children’s ToM development when relevant control variables were included in the analyses. Additionally, two correlational analyses were conducted to address the research question that whether children’s age and expressive vocabulary correlate with parental reports of ToM understandings. No correlation was found between age and ToM ability. However, there was a significant correlation between children’s expressive language and ToM, giving further support to the social constructivist account. An independent samples t-test to test the gender effect on parental-report ToM yielded no significant results. Evidence of Internal consistency, content validity, and construct validity for the two translated questionnaires was given. However, accurate estimation of the psychometric properties of the two translated measures requires more research. Finally, Implications and future directions for research on the relationship between maternal mental state talk and ToM development in diverse and larger samples from a longitudinal lens were discussed.

CONTEXT Studies find surgery superior to medications in the treatment of primary aldosteronism (PA). It would be ideal to compare surgical and medical therapy in patients with unilateral PA only, who have the option between these treatment modalities. However, this is challenging as most patients with unilateral PA on adrenal vein sampling (AVS) undergo surgery. OBJECTIVE To compare outcomes of surgery and medications in patients with confirmed or likely unilateral PA. DESIGN Retrospective cohort study of 274 patients with PA managed at two referral centres from 2000 to 2019. PATIENTS 154 patients identified with unilateral PA using AVS and a validated clinical prediction model were treated with surgical (n = 86) or medical (n = 68) therapy. MEASUREMENTS Primary outcome was a composite incident cardiovascular event comprising acute myocardial infarction, coronary revascularization, stroke, atrial fibrillation or congestive cardiac failure. Secondary outcomes were clinical and biochemical control. RESULTS Cardiovascular outcomes were comparable, with the surgery group having an adjusted hazard ratio of 0.93 (95% CI: 0.32-2.67), p = .89. Both treatments improved clinical and biochemical control, but surgery resulted in better systolic blood pressure, 133.0 ± 11.7 mmHg versus 137.9 ± 14.6 mmHg, p = .02, and lower defined daily dosages of antihypertensive medications, 1.0 (IQR 0.0-2.0) versus 2.6 (IQR 0.8-4.3), p

Introduction Patients with primary aldosteronism (PA) have increased cardiovascular risk, and there are concerns about the efficacy of medical therapy. Objective We aimed to assess long-term tolerability and efficacy of medical therapy in PA patients. Methods We conducted a retrospective study on 201 PA patients treated with medical therapy (spironolactone, eplerenone, or amiloride) from 2000 to 2020 at 2 tertiary centers. Clinical and biochemical control and side effects were assessed. Results Among 155 patients on long-term medications, 57.4% achieved blood pressure (BP) 1 ng/mL/h. Concordance of biochemical control using potassium and renin levels was 49.1%. Side effects were experienced by 52.3% of patients, with 10.3% switching, 22.6% decreasing dose, and 11.0% stopping medications. Risk factors for side effects were spironolactone use, dose ≥ 50 mg, treatment duration ≥1 year, male gender, and unilateral PA. Patients with unilateral PA used higher spironolactone doses vs bilateral (57 vs 50 mg, P < 0.001) and had more side effects (63.2% vs 41.8%, P = 0.008). Forty-six unilateral PA patients who underwent surgery after initial medical therapy experienced improved BP (systolic from 141 to 135 mmHg, P = 0.045; diastolic from 85 to 79 mmHg, P = 0.002). Conclusion Dose-dependent side effects limit efficacy of medical therapy in PA. Future prospective studies should assess the best monitoring strategy for biochemical control during long-term medical therapy. For unilateral PA, surgery remains preferable, yielding better control with less long-term side effects.

© 2020 Elsevier Ltd In practical grid-connected photovoltaic systems, faulty modules for small-scale photovoltaic arrays need to be accurately located, while the same strategy to locate each faulty module for large-scale arrays would imply high investment cost due to a large number of sensors needed. Therefore, to reduce the number of sensors and save fault monitoring investment, it suffices to identify where fault happens in a module block, which consists of several modules connected in series. For this purpose, this paper proposes a fault-locating strategy to identify faulty module blocks for large-scale arrays, where voltage sensors are deployed by differentiating the parity of string numbers in the array to acquire the terminal voltages of the module blocks between adjacent strings, and the fault locating rules for open circuit, short circuit, degradation and partial shading faults are formulated. With the help of MATLAB/Simulink platform, the proposed strategy is tested in one small-size array and two large-scale arrays, and the testing results demonstrate that the proposed strategy can locate the single fault case, multiple faults of single-type, as well as mixed faults of different sub-arrays. To summarize, the proposed fault-locating method has higher locating accuracy, lower implementation cost and wiring complexity, and is easily integrable with existing photovoltaic systems.

Introduction Studies show trabecular bone score (TBS) may provide information regarding bone quality independent of bone mineral density (BMD) in type 2 diabetes (DM2) patients. We analyzed our Southeast Asian severe osteoporotic hip fracture patients to study these differences. Methods We conducted a retrospective cross-sectional analysis of subjects admitted to Changi General Hospital, Singapore with severe osteoporotic hip fractures from 2014–2017 who had BMD performed. Electronic records were reviewed and subjects were classified as having diabetes according to the WHO 2019 criteria. DM2 patients were classified according to their HbA1c into well controlled (HbA1c < 7%) and poorly controlled (HbA1c ≥ 7%) DM2. Results Elderly patients with hip fractures present with average femur neck T scores at the osteoporotic range, however those with DM2 had higher BMD and TBS values compared to non DM2 patients. These differences were statistically significant in elderly women—poorly controlled elderly DM2 women with hip fracture had the highest total hip T-score (-2.57 ± 0.86) vs (-2.76 ± 0.96) in well controlled DM2 and (-3.09 ± 1.01) in non DM2 women with hip fracture, p < 0.001. In contrast, TBS scores were lower in poorly controlled DM2 women with hip fracture compared to well controlled DM2 women with hip fracture (1.22 ± 0.11) vs (1.24 ± 0.09), but these were still significantly higher compared to non DM2 women with hip fracture (1.19 ± 0.10), p < 0.001. In elderly men with hip fractures, univariate analysis showed no statistically significant differences in TBS or hip or LS BMD between those with poorly controlled DM2, well controlled DM2 and non DM2. The differences in TBS and BMD remained significant in all DM2 women with hip fractures even after adjustments for potential confounders. Differences in TBS and BMD in poorly controlled DM2 men with hip fractures only became significant after accounting for potential confounders. However, upon inclusion of LS BMD into the multivariate model these differences were attenuated and remained significant only between elderly women with well controlled DM2 and non DM2 women with hip fractures. Conclusions Elderly patients with DM2 and severe osteoporosis present with hip fractures at a higher BMD and TBS values compared to non DM2 patients. These differences were significant after adjustment for confounders in all DM2 women and poorly controlled DM2 men with hip fractures, TBS differences were attenuated with the inclusion LS BMD. Further studies are needed to ascertain differences in BMD and TBS in older Southeast Asian DM2 patients with variable glycemic control and severe osteoporosis.

Trehalose is commonly used as a protein stabilizer in spray dried protein formulations delivered via the pulmonary route. Spray dried trehalose formulations are highly hygroscopic, which makes them prone to deliquescence and recrystallization when exposed to moisture, leading to impairment in aerosolization performance. The main aim of this study was to investigate and compare the effect of hydrophobic amino acids (i.e. L-leucine and L-isoleucine) in enhancing aerosolization performance and in mitigating moisture-induced changes in spray dried trehalose formulations. Trehalose was spray dried with 20–60% w/w of amino acid (i.e. L-leucine or L-isoleucine). The spray dried formulations were stored at 25 °C/50% RH for 28 days. Solid state characterization and in vitro aerosolization performance studies were performed on the spray dried formulations before and after storage. The addition of 20–60% w/w of amino acid (i.e. L-leucine or L-isoleucine) improved the emitted fractions of spray dried trehalose formulations from a dry powder inhaler. However, ≥ 40% w/w of L-leucine/L-isoleucine was needed to prevent recrystallization of trehalose in the formulations when exposed to 25 °C/50% RH for 28 days. X-ray photoelectron spectroscopy (XPS) demonstrated that samples with 40–60% w/w L-isoleucine had more amino acid on the surfaces of the particles compared to their L-leucine counterparts. This may explain the greater ability of the L-isoleucine (40–60% w/w) samples to cope with elevated humidity compared to L-leucine samples of the same concentrations, as observed in the dynamic vapour sorption (DVS) studies. In conclusion, this study demonstrated that both L-leucine and L-isoleucine were effective in enhancing aerosolization performance and mitigating moisture-induced reduction in aerosolization performance in spray dried trehalose formulations. L-isoleucine proved to be superior to L-leucine in terms of its moisture protectant effect when incorporated at the same concentration in the formulations.

The optimal design of oral amorphous formulations benefits from the use of excipients to maintain drug supersaturation and thus ensures adequate absorption during intestinal transit. The use of surfactants for the maintenance of supersaturation in amorphous formulations has not been investigated in detail. The main aim of this study was to investigate the effect of surfactant on the dissolution behavior of neat amorphous drug and binary polymer based solid dispersion. Indomethacin was used as the model drug and the surfactants studied were polysorbate 80 and poloxamer 407. The presence of surfactants (alone or in combination with polymers) in the buffer was detrimental to the dissolution of neat amorphous indomethacin, suggesting that the surfactants promoted the crystallization of neat amorphous indomethacin. In contrast, the presence of surfactants (0.01% w/v) in the buffer resulted in a significant improvement on the dissolution behavior of binary polymer based solid dispersion. Incorporating the surfactant to the formulation to form ternary solid dispersion adversely affected the dissolution behavior. In conclusion, the use of surfactants (as wetting or solubilization agents) in dissolution studies of neat amorphous drugs requires prudent consideration. The design of amorphous formulations with optimal dissolution performance requires the appropriate selection of a combination of excipients and consideration of the method of introducing the excipients.

Aims: The abdominal region is the most common location for continuous glucose monitor (CGM) sensor insertion. However, a paucity of post-marketing data is available to demonstrate intra-individual consistency of CGM readings at different abdominal insertion sites. Methods: Healthy adults (fasting glucose (FG) < 5.5 mmol/L; BMI < 30 kg/m2) were recruited and a CGM sensor was placed on each side of the abdomen. Postprandial and continuous 48-h interstitial glucose levels were analyzed. Results: There was no significant difference in the 3-h postprandial glucose (PPG) level derived from the left versus right CGM, which remained non-significant after adjusting for waist circumference or FG. Among the glucose levels recorded over 48-h, values on the left site were greater in 3.6% of the data points (p < 0.05). After adjusting for waist circumference, only 0.5% of the glucose values remained significantly greater on the left (p < 0.05). When adjusted for FG, similar results were observed. For both PPG and 48-h readings, the mean absolute relative difference was not significant between the two abdominal sites. Conclusions: CGM-derived glucose measures were highly consistent between the left and right abdomen during both the postprandial and post-absorptive periods.

Background In contrast to the effects of preterm birth, the extent to which shorter gestational age affects the cardiorespiratory fitness ( CRF ) levels of individuals who were born at term (ie, between 37 and 42 weeks) is largely unknown. The aim of this study was to examine whether life‐course CRF levels varied across different gestational ages within the at‐term range. Methods and Results The association between gestational age (in weeks) obtained from Child Health Services records and CRF , estimated from field and laboratory tests and expressed by maximal oxygen uptake level through adolescence to young adulthood, was examined in 791 participants in the Northern Ireland Young Hearts Study, all singletons born at term. Longitudinal data were analyzed with generalized estimating equations, accounting for important potential confounders. Mean levels of CRF were 45.6, 43.7, and 33.0 mL/kg per minute when participants were aged 12, 15, and 22 years, respectively. After adjustment for confounders, each week increase in gestational age was associated with 0.46 mL/kg per minute (95% confidence interval , 0.14–0.79) in CRF . Compared with individuals born full term (39–40 weeks, n=533) or late term (41–42 weeks, n=148), those who were born early term (37–38 weeks, n=110) had a higher incidence of poor CRF (risk ratio, 1.57; 95% confidence interval , 1.14–2.16). The changes in CRF through adolescence to young adulthood were similar across groups, with those born early term consistently displaying the lowest CRF. Conclusions These findings suggest that early‐term births within the at‐term range are linked to poorer CRF through adolescence to young adulthood, and may have important clinical and public health implications for policies about (avoidable) early‐term deliveries given their recent increasing trends.

Low-frequency Raman spectroscopy, which directly probes phonon lattice modes of crystal structures, has much unexplored potential for sensitive qualitative and quantitative analysis of crystallinity in drugs and excipients. In this study, the level of crystallinity in tablets containing amorphous drug is quantified using low-frequency Raman spectroscopy in concert with chemometrics for the first time. Importantly, these data are directly compared to simultaneously obtained mid-frequency Raman spectra, as well as to FT-Raman data, which is commonly used for such quantification. Griseofulvin was used as a model drug. The PLS model using FT-Raman spectroscopy gave a root mean squared error of prediction (RMSEP) of 0.65%. The PLS models of the low- and mid-frequency regions using a charge coupled device (CCD) based Raman system with 785 nm excitation gave an RMSEP = 1.2% when using the low-frequency region (5–120 cm −1 ) and RMSEP = 1.4% for the mid-range frequencies (520–1740 cm −1 ). The recrystallization profiles determined using the various Raman techniques and their associated models were similar. The FT-Raman and the low frequency Raman systems were able to detect and quantify crystallinity in stored amorphous samples earlier than the mid-frequency 785 nm Raman system. Overall, this study suggests that low-frequency Raman spectroscopy has at least equally good performance compared to mid-frequency Raman for quantitative analysis of crystallinity in the pharmaceutical setting. More generally, the much stronger Raman scattering in the low-frequency region combined with the intrinsic spectral differences between amorphous and crystalline materials may prove advantageous for some analyses.

Decreases in the mean gestational age of term deliveries have been reported over the past decade in several developed countries, linked to increases in the rates of planned births by labour induction and/or pre-labour caesarean sections. In contrast to the effects of pre-term birth, the extent to which lower gestation age within the at-term range (i.e. 37 to 42 weeks) affects individuals’ cardiorespiratory fitness (CRF) health is largely unknown, however. We therefore examined the association between gestational age, accounting for other important perinatal covariates (obtained from the NI Child Health Services’ records), and CRF (VO 2 max) as measured through adolescence to young adulthood in 842 (51.5% female) participants in the NIYHP (all singletons born at term, 98% of whom with birth weight greater than 2.5 kg). Participants’ mean levels of CRF were 45.6 ± 4.8, 43.7 ± 6.8 and 32.9 ± 9.8 ml/kg/min at the ages of 12, 15 and 22 years, respectively. With the use of GEE analyses adjusted for age, sex, socio economic status, birth weight z-scores (relative to UK’s 1990 reference), breast-feeding practices and duration, maternal age at child’s birth and delivery mode, we found that each week increase in gestational age was associated with 0.44 ml/kg/min (95% CI 0.13 to 0.75) higher levels of CRF throughout the whole longitudinal period (p=0.005). Further adjustments for participants’ height, body fatness and maturational level throughout the longitudinal period only attenuated this association slightly [to 0.38 ml/kg/min (95% CI 0.12 to 0.65), p=0.005]. There were no significant interactions between gestational age and sex or participants’ age at the time of CRF assessment, indicating that the decreases in CRF over time were similar across the different gestational ages, with those born early term displaying consistently lower levels throughout the longitudinal period. Finally, each week increase in gestation age was associated with lower risk of poor CRF through adolescence to young adulthood as defined according to current age and sex-specific health-reference values of VO 2 max: RR=0.89 (95% 0.81 to 0.97), p=0.008. These findings suggest that lower gestational age, even within the at-term range , may be a key determinant of poorer CRF as each additional week conferred benefits. This aspect may have been neglected by the over-simplistic characterisation of individuals born at-term as a homogeneous group and may have public health and clinical implications for policies around planned deliveries, given the current trends.

Purpose To investigate the effect of compression on the crystallization behavior in amorphous tablets using sum frequency generation (SFG) microscopy imaging and more established analytical methods. Method Tablets containing neat amorphous griseofulvin with/without excipients (silica, hydroxypropyl methylcellulose acetate succinate (HPMCAS), microcrystalline cellulose (MCC) and polyethylene glycol (PEG)) were prepared. They were analyzed upon preparation and storage using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM) and SFG microscopy. Results Compression-induced crystallization occurred predominantly on the surface of the neat amorphous griseofulvin tablets, with minimal crystallinity being detected in the core of the tablets. The presence of various types of excipients was not able to mitigate the compression-induced surface crystallization of the amorphous griseofulvin tablets. However, the excipients affected the crystallization rate of amorphous griseofulvin in the core of the tablet upon compression and storage. Conclusion SFG microscopy can be used in combination with ATR-FTIR spectroscopy and SEM to understand the crystallization behaviour of amorphous tablets upon compression and storage. When selecting excipients for amorphous formulations, it is important to consider the effect of the excipients on the physical stability of the amorphous formulations.

Milling is an attractive method to prepare amorphous formulations as it does not require the use of solvents and is suitable for thermolabile drugs. One of the key critical quality attributes of milled amorphous formulations is their dissolution behavior. However, there are limited studies that have investigated the relationship between degree of disorder induced by milling and dissolution behavior. The main aim of this study was to identify the analytical technique used to characterize degree of disorder that correlates best with the recrystallization behavior during dissolution of milled glibenclamide samples. Solid state and surface changes during dissolution of milled glibenclamide samples were monitored in order to elucidate the processes that influence the dissolution behavior of milled glibenclamide samples. Glibenclamide was ball milled for different durations and analyzed using X-ray powder diffractometry (XRPD), Raman spectroscopy and differential scanning calorimetry (DSC). Recrystallization during dissolution of the milled amorphous materials was investigated using an in situ Raman setup. SEM was used to monitor the surfaces of the compacts during dissolution. XRPD, Raman spectroscopy and DSC indicated that glibenclamide was fully amorphous after milling for 30, 60, and 120 min, respectively. 'DSC amorphous' (i.e. fully amorphous according to the onset of crystallization obtained from DSC) glibenclamide samples experienced negligible recrystallization which had no effect on the dissolution profiles. Samples that were not 'DSC amorphous' experienced recrystallization which resulted in a decrease in dissolution rate. Unexpected elevated dissolution rate was observed initially during dissolution for samples milled for 15 to 45 min, and this was related to particle loss from surfaces of the disks during dissolution. In conclusion, the onset of crystallization obtained from DSC best predicts the recrystallization of glibenclamide during dissolution. Recrystallization and particle loss from the surface of the dissolution should be considered when interpreting the dissolution data of milled glibenclamide samples.

This paper aims to examine the effects of oil price shocks on economic sectors in Malaysia. A unit root test was conducted, in which data were shown to be non-stationary in all levels, and stationary in the first difference for all variables. The co-integration model was applied, and the results indicated that one co-integrating equation exists, suggesting the long-term effects of oil prices on the agriculture, construction, manufacturing, and transportation sectors. Finally, Grange causality test was performed, and the results implied that in Malaysia, oil price shocks can affect agriculture, similar to Hanson et al. (2010). Oil price instability also influences the performance of the agriculture sector, contrary to the results of Alper and Torul (2009). In addition, the construction sector was found to be dependent on oil prices. Therefore, the current study has an important implication for the Malaysian government in formulating policies on oil prices. The Malaysian government needs to control the price to ensure that unstable price will not harm the agriculture, manufacturing, and construction sectors.