Return on investment of fracture liaison services: a systematic review and analysis.

Fracture liaison services (FLS) have been proven clinically effective and cost-effective in preventing subsequent fractures among patients with an existing fragility fracture. Little is known about their monetary benefits such as their return on investment (ROI). This systematic review aimed to investigate the ROI of FLS and identify the FLS characteristics with better ROI. Studies on the cost-effectiveness of FLS published between January 2000 and December 2022 were searched from MEDLINE, EMBASE, PubMed, and Cochrane Central. Two independent reviewers conducted study selection and data extraction. ROI was calculated based on the difference between monetary benefits and FLS costs divided by the FLS costs. Subgroup analysis of ROI was performed across FLS types and FLS design details. A total of 23 FLS were included in this review. The majority of them were targeting patients aged over 50 years having fractures without identified sites. The mean ROI of these FLS was 10.49 (with a median ROI of 7.57), and 86.96% of FLS had positive ROI. FLS making treatment recommendations yielded the highest ROI (with a mean ROI of 18.39 and a median of 13.60). Incorporating primary care providers (with a mean ROI of 16.04 and a median of 13.20) or having them as program leaders (with a mean ROI of 12.07 and a median of 12.07) has demonstrated a high ROI. FLS for specific fracture sites had great monetary return. Intensive FLS such as type A and B FLS programs had higher ROI than non-intensive type C and D FLS. This review revealed a 10.49-fold monetary return of FLS. Identified characteristics contributing to greater economic return informed value-for-money FLS designs. Findings highlight the importance of FLS and the feasibility of expanding their contribution in mitigating the economic burden of osteoporotic fracture and are conducive to the promotion of FLS internationally.

Comparison of speech and music input in North American infants' home environment over the first 2 years of life.

Infants are immersed in a world of sounds from the moment their auditory system becomes functional, and experience with the auditory world shapes how their brain processes sounds in their environment. Across cultures, speech and music are two dominant auditory signals in infants' daily lives. Decades of research have repeatedly shown that both quantity and quality of speech input play critical roles in infant language development. Less is known about the music input infants receive in their environment. This study is the first to compare music input to speech input across infancy by analyzing a longitudinal dataset of daylong audio recordings collected in English-learning infants' home environments, at 6, 10, 14, 18, and 24 months of age. Using a crowdsourcing approach, 643 naïve listeners annotated 12,000 short snippets (10 s) randomly sampled from the recordings using Zooniverse, an online citizen-science platform. Results show that infants overall receive significantly more speech input than music input and the gap widens as the infants get older. At every age point, infants were exposed to more music from an electronic device than an in-person source; this pattern was reversed for speech. The percentage of input intended for infants remained the same over time for music while that percentage significantly increased for speech. We propose possible explanations for the limited music input compared to speech input observed in the present (North American) dataset and discuss future directions. We also discuss the opportunities and caveats in using a crowdsourcing approach to analyze large audio datasets. A video abstract of this article can be viewed at https://youtu.be/lFj_sEaBMN4 RESEARCH HIGHLIGHTS: This study is the first to compare music input to speech input in infants' natural home environment across infancy. We utilized a crowdsourcing approach to annotate a longitudinal dataset of daylong audio recordings collected in North American home environments. Our main results show that infants overall receive significantly more speech input than music input. This gap widens as the infants get older. Our results also showed that the music input was largely from electronic devices and not intended for the infants, a pattern opposite to speech input.

Machine-learning-based performance comparison of two-dimensional (2D) and three-dimensional (3D) CT radiomics features for intracerebral haemorrhage expansion.

AIM: To investigate the value of non-contrast CT (NCCT)-based two-dimensional (2D) radiomics features in predicting haematoma expansion (HE) after spontaneous intracerebral haemorrhage (ICH) and compare its predictive ability with the three-dimensional (3D) signature. MATERIALS AND METHODS: Three hundred and seven ICH patients who received baseline NCCT within 6 h of ictus from two stroke centres were analysed retrospectively. 2D and 3D radiomics features were extracted in the manner of one-to-one correspondence. The 2D and 3D models were generated by four different machine-learning algorithms (regularised L1 logistic regression, decision tree, support vector machine and AdaBoost), and the receiver operating characteristic (ROC) curve was used to compare their predictive performance. A robustness analysis was performed according to baseline haematoma volume. RESULTS: Each feature type of 2D and 3D modalities used for subsequent analyses had excellent consistency (mean ICC >0.9). Among the different machine-learning algorithms, pairwise comparison showed no significant difference in both the training (mean area under the ROC curve [AUC] 0.858 versus 0.802, all p>0.05) and validation datasets (mean AUC 0.725 versus 0.678, all p>0.05), and the 10-fold cross-validation evaluation yielded similar results. The AUCs of the 2D and 3D models were comparable either in the binary or tertile volume analysis (all p>0.5). CONCLUSION: NCCT-derived 2D radiomics features exhibited acceptable and similar performance to the 3D features in predicting HE, and this comparability seemed unaffected by initial haematoma volume. The 2D signature may be preferred in future HE-related radiomic works given its compatibility with emergency condition of ICH.

One-pot heat-up synthesis of short-wavelength infrared, colloidal InAs quantum dots.

III-V colloidal quantum dots (QDs) promise Pb and Hg-free QD compositions with which to build short-wavelength infrared (SWIR) optoelectronic devices. However, their synthesis is limited by the availability of group-V precursors with controllable reactivities to prepare monodisperse, SWIR-absorbing III-V QDs. Here, we report a one-pot heat-up method to synthesize ∼8 nm edge length (∼6.5 nm in height) tetrahedral, SWIR-absorbing InAs QDs by increasing the [In3+]:[As3+] ratio introduced using commercially available InCl3 and AsCl3 precursors and by decreasing the concentration and optimizing the volume of the reducing reagent superhydride to control the concentration of In(0) and As(0) intermediates through QD nucleation and growth. InAs QDs are treated with NOBF4, and their deposited films are exchanged with Na2S to yield n-type InAs QD films. We realize the only colloidal InAs QD photoconductors with responsivity at the technologically important wavelength of 1.55 µm.

[Severe cardiotoxic characteristics associated with allogeneic hematopoietic stem cell transplantation preconditioning in patients with aplastic anemia].

Objective: To delineate the clinical characteristics and outcomes associated with severe cardiac toxicity during the preconditioning phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia (AA). Methods: This retrospective case series study included 31 patients with severe AA who underwent allo-HSCT and were diagnosed with severe cardiac toxicity at the Hematology Department of Peking University People's Hospital from August 2012 to June 2022. The clinical manifestations of severe cardiac toxicity observed during the preconditioning process were assessed. Patient survival was assessed using the Kaplan-Meier method. Results: In this cohort of 31 patients, the median follow-up period was 9 days (range: 4-365 days). Severe cardiac toxicity manifested within 6 days after the initial cyclophosphamide (Cy) administration. Twenty patients died within 30 days of initiating Cy preconditioning, of which 16 patients died due to severe cardiac toxicity within 25 days. Patients whose cardiac function improved within 30 days post-preconditioning showed a median survival duration of 222 days (n=11). Troponin I (TNI) levels in patients who died within 30 days of initiating Cy preconditioning began increasing on day 5 post-Cy, peaking sharply by day 9 after a notable rise on day 8. B-type natriuretic peptide (BNP) levels in patients who died within 30 days of initiating Cy preconditioning started to rise from day 1, stabilized between days 2 and 5, and then doubled daily from days 6 to 8, remaining elevated thereafter. Notably, the initial increases in BNP and TNI correlated with electrocardiogram (ECG) signs of low voltage and T-wave inversion in 83.87% of cases (n=26). Most patients (n=28, 90.32%) were administered corticosteroid therapy. In those with restored cardiac function, the ejection fraction returned to >50% within 30 days of initiating Cy preconditioning. Conclusions: Patients with severe cardiac toxicity during the preconditioning phase of allo-HSCT typically exhibit early, sustained, and marked elevations in myocardial damage markers, including BNP and TNI, accompanied by ECG abnormalities following Cy administration, with BNP often increasing first. These indicators are associated with rapid disease progression and high mortality. Prompt initiation of treatment upon clinical diagnosis is critical for improving survival outcomes.

[Evaluation of semicircular canal and otolith graviceptive pathway function in patients diagnosed with motion sickness disorder based on the diagnostic criteria of the Bárány society].

Objective: To investigate the altered function of the semicircular canal and otolith graviceptive pathway in patients diagnosed with motion sickness disorder (MSD) based on the diagnostic criteria of the Bárány society, and explore its relevance to the pathogenesis of MSD. Methods: This is a case-control study. Twenty patients with MSD and age-and sex-matched healthy controls without a history of MSD from the Department of Neurology of Aerospace Center Hospital between March and August 2022 were recruited. All subjects completed the motion sickness susceptibility questionnaire-short version (MSSQ-short) and the motion sickness assessment questionnaire (MSAQ). Canal function was evaluated using caloric stimulation test and video head impulse test (vHIT), and subjective visual vertical/horizontal (SVV/SVH) and vestibular evoked myogenic potential (VEMP) were employed to assess otolith graviceptive function. Differences in vestibular function and correlations between the two groups were analyzed. Results: Each group consisted of 20 cases (9 males and 11 females). The mean age of the MSD and control groups was (26.9±3.9) years and (27.0±3.4) years, respectively. The scores of MSSQ-short [27.0 (22.5, 38.8) vs 1.2 (0, 3.2), P<0.001] and MSAQ [70.1 (54.5, 78.1) vs 11.8 (11.1, 13.9), P<0.001] were significantly higher in the MSD group compared with those of the control group. Evaluation of canal function revealed a significantly higher incidence of caloric stimulation intolerance in MSD patients (60.0%, 12/20) compared with that of the control group (20.0%, 4/20) (P=0.010). Evaluation of otolith graviceptive pathway indicated no significant difference in SVV, SVH and cervical VEMP (cVEMP) abnormality rates between the two groups (all P>0.05). The ocular VEMP (oVEMP) abnormality rate was significantly higher in the MSD group (55.0%, 11/20) than that of the control group (10.0%, 2/20) (P=0.002), with a delayed P1-wave latency compared with the control group [(18.4±1.2) ms vs (17.6±0.8) ms, P=0.018]. Further correlation analysis revealed that P1-wave latency in oVEMP was positively correlated with MSSQ-short (r=0.486, P=0.002) and MSAQ (r=0.391, P=0.015) scores, and duration of caloric intolerance symptoms (r=0.377, P=0.004). Conclusion: The presence of hypersensitivity to caloric stimulation and delayed latency of otolith function in patients with MSD suggests a "separation" between semicircular canal and otolithic function, which may be related to sensory conflict.

[Epidemiological characteristics of a local cluster epidemic caused by the BA.2 evolutionary branch of Omicron variant].

Descriptive epidemiological methods were used to analyze the epidemiological characteristics of the local cluster of COVID-19 in the logistic park of Yuhang District in Hangzhou in March 2022. The cluster epidemic was detected by a case who actively visited the fever clinic. The epidemic lasted for 8 days, and a total of 58 cases (53 workers, 2 students, 1 farmer, 1 teacher and 1 unemployed) were found, including 40 males and 18 females. The age was (33.29±12.22) years. There cases were mainly in Yuhang District (48 cases, 82.77%) and Shangcheng District (7 cases, 12.07%) of Hangzhou. The real-time regeneration number peaked at 2.31 on March 10th and decreased to 0.37 on March 15th. The sequencing result of the indicated case was 100% homologous with the sequence uploaded from South Korea on March 4th, 2022.

Learning Intention-Aware Policies in Deep Reinforcement Learning.

Deep reinforcement learning (DRL) provides an agent with an optimal policy so as to maximize the cumulative rewards. The policy defined in DRL mainly depends on the state, historical memory, and policy model parameters. However, we humans usually take actions according to our own intentions, such as moving fast or slow, besides the elements included in the traditional policy models. In order to make the action-choosing mechanism more similar to humans and make the agent to select actions that incorporate intentions, we propose an intention-aware policy learning method in this letter To formalize this process, we first define an intention-aware policy by incorporating the intention information into the policy model, which is learned by maximizing the cumulative rewards with the mutual information (MI) between the intention and the action. Then we derive an approximation of the MI objective that can be optimized efficiently. Finally, we demonstrate the effectiveness of the intention-aware policy in the classical MuJoCo control task and the multigoal continuous chain walking task.

Incidence and characteristics of aspiration pneumonia in adults in Beijing, China, 2011-2017.

OBJECTIVES: This study aimed to estimate aspiration pneumonia (AP) incidence and describe comorbid characteristics and mortality in Beijing, China. STUDY DESIGN: A historical cohort study was conducted based on medical claim records. METHODS: Patients admitted with a primary diagnosis of AP were identified from approximately 12 million adults who enrolled in the Urban Employee Basic Medical Insurance program in Beijing, China, from January 2011 to December 2017. The incidences of AP and pneumonia with risk factors for aspiration (PRFA) were estimated by a Poisson distribution. The estimated annual percentage change was reported to represent the average percentage change in incidence per year. Characteristics and 6-month and 1-year all-cause mortality rates for AP and suspected AP patients were described and compared with community-acquired pneumonia (CAP). RESULTS: The incidence rates of hospitalized AP and PRFA were 9.4 (95% confidence interval [CI]: 7.6, 11.3) and 102.9 (95% CI: 95.8, 110.3) per 100,000 person-years, respectively. The incidences increased rapidly with age and were stable across the observed years. Patients with AP and PRFA possessed a greater burden of comorbidities than CAP (mean age-adjusted Charlson comorbidity indices for AP: 7.72, PRFA: 7.83, and CAP: 2.84). The 6-month and 1-year all-cause mortality rates for those with AP and PRFA were higher than those for patients with CAP (6-month mortality, AP: 35.2%, PRFA: 21.8%, CAP: 11.1%; 1-year mortality, AP: 42.7%, PRFA: 26.6%, CAP: 13.2%). CONCLUSIONS: The incidence of AP and PRFA in Beijing was reported, presenting a full picture of the disease burden. The results provide baseline information for AP prevention.

[Endovascular therapy accompanied by spontaneous portosystemic shunts for overt hepatic encephalopathy].

Objective: To preliminarily evaluate the safety and efficacy of shunt-related interventional therapy accompanied with spontaneous portosystemic shunts (SPSS) in patients with hepatic encephalopathy (HE). Methods: Case data on six patients who underwent interventional therapy accompanied by SPSS for HE from January 2017 to March 2021 were collected to evaluate the efficacy and postoperative complications. Results: All six patients underwent SPSS. Four patients had hepatitis B cirrhosis; one had alcoholic cirrhosis; and one had hepatic arterioportal fistula-induced portal hypertension. Child-Pugh liver function scores were C and B in three and three cases, respectively. The SPSS type was gastrorenal shunt in two cases; portal-thoracic-azygos venous in two cases; portal-umbilical-iliac venous in one case; and portal-splenic venous - inferior vena cava in one case. Two of them had previously had a transjugular intrahepatic portosystemic shunt (TIPS), and there were SPSS prior to TIPS. Five cases (5/6) successfully underwent shunt embolization, and one case (1/6) underwent stent implantation for flow restriction (portal-umbilical-iliac vein). The technical success rate was 100%. HE did not recur during hospitalization or the three-month follow-up period. However, one case had a recurrence of HE within a year after surgery and was treated symptomatically, while another experienced gastrointestinal bleeding a year after surgery.. Conclusion: SPSS embolization or flow restriction is effective and safe for improving HE patients' symptoms.

Development of infants' neural speech processing and its relation to later language skills: A MEG study.

The 'sensitive period' for phonetic learning (∼6-12 months) is one of the earliest milestones in language acquisition where infants start to become specialized in processing speech sounds in their native language. In the last decade, advancements in neuroimaging technologies for infants are starting to shed light on the underlying neural mechanisms supporting this important learning period. The current study reports on a large longitudinal dataset with the aim to replicate and extend on two important questions: 1) what are the developmental changes during the 'sensitive period' for native and nonnative speech processing? 2) how does native and nonnative speech processing in infants predict later language outcomes? Fifty-four infants were recruited at 7 months of age and their neural processing of speech was measured using Magnetoencephalography (MEG). Specifically, the neural sensitivity to a native and a nonnative speech contrast was indexed by the mismatch response (MMR). They repeated the measurement again at 11 months of age and their language development was further tracked from 12 months to 30 months of age using the MacArthur-Bates Communicative Development Inventory (CDI). Using an a priori Region-of-Interest (ROI) approach, we observed significant increases for the Native MMR in the left inferior frontal region (IF) and superior temporal region (ST) from 7 to 11 months, but not for the Nonnative MMR. Complementary whole brain comparison revealed more widespread developmental changes for both contrasts. However, only individual differences in the left IF and ST for the Nonnative MMR at 11 months of age were significant predictors of individual vocabulary growth up to 30 months of age. An exploratory machine-learning based analysis further revealed that whole brain time series for both Native and Nonnative contrasts can robustly predict later outcomes, but with very different underlying spatial-temporal patterns. The current study extends our current knowledge and suggests that native and nonnative speech processing may follow different developmental trajectories and utilize different mechanisms that are relevant for later language skills.

Brain myelination at 7 months of age predicts later language development.

Between 6 and 12 months of age there are dramatic changes in infants' processing of language. The neurostructural underpinnings of these changes are virtually unknown. The objectives of this study were to (1) examine changes in brain myelination during this developmental period and (2) examine the relationship between myelination during this period and later language development. Macromolecular proton fraction (MPF) was used as a marker of myelination. Whole-brain MPF maps were obtained with 1.25 mm3 isotropic spatial resolution from typically developing children at 7 and 11 months of age. Effective myelin density was calculated from MPF based on a linear relationship known from the literature. Voxel-based analyses were used to identify longitudinal changes in myelin density and to calculate correlations between myelin density at these ages and later language development. Increases in myelin density were more predominant in white matter than in gray matter. A strong predictive relationship was found between myelin density at 7 months of age, language production at 24 and 30 months of age, and rate of language growth. No relationships were found between myelin density at 11 months, or change in myelin density between 7 and 11 months of age, and later language measures. Our findings suggest that critical changes in brain structure may precede periods of pronounced change in early language skills.

Development of executive function-relevant skills is related to both neural structure and function in infants.

The development of skills related to executive function (EF) in infancy, including their emergence, underlying neural mechanisms, and interconnections to other cognitive skills, is an area of increasing research interest. Here, we report on findings from a multidimensional dataset demonstrating that infants' behavioral performance on a flexible learning task improved across development and that the task performance is highly correlated with both neural structure and neural function. The flexible learning task probed infants' ability to learn two different associations, concurrently, over 16 trials, requiring multiple skills relevant to EF. We examined infants' neural structure by measuring myelin density in the brain, using a novel macromolecular proton fraction (MPF) mapping method. We further examined an important neural function of speech processing by characterizing the mismatch response (MMR) to speech contrasts using magnetoencephalography (MEG). All measurements were performed longitudinally in monolingual English-learning infants at 7- and 11-months of age. At the group level, 11-month-olds, but not 7-month-olds, demonstrated evidence of learning both associations in the behavioral task. Myelin density in the prefrontal region at 7 months of age was found to be highly predictive of behavioral task performance at 11 months of age, suggesting that myelination may support the development of these skills. Furthermore, a machine-learning regression analysis revealed that individual differences in the behavioral task are predicted by concurrent neural speech processing at both ages, suggesting that these skills do not develop in isolation. Together, these cross-modality results revealed novel insights into EF-related skills. HIGHLIGHT: Monolingual infants demonstrated flexible learning on a task requiring executive function skills at 11 months, but not at 7 months. Infants' myelin density at 7 months is highly predictive of their behavioral performance in the flexible learning task at 11 months of age. Individual differences in the flexible learning task performance are also correlated with concurrent neural processing of speech at both ages.

The influence of CYP2R1 polymorphisms and gene-obesity interaction with hypertension risk in a Chinese rural population.

BACKGROUND AND AIMS: Several studies have reported that variants in CYP2R1 have been linked with an increased risk of hypertension. However, the interaction between CYP2R1 variants and environmental factors on the susceptibility of hypertension remained unclear. Therefore, this study evaluated the influence of CYP2R1 polymorphisms on hypertension susceptibility, and explored the interaction effect of CYP2R1 variations and obesity on the disease. METHODS AND RESULTS: We included 766 incident hypertension cases matched with non-hypertension controls in a 1:1 ratio by sex, age (within 3 years). Two loci in CYP2R1 gene (rs10766197 and rs12794714) were genotyped by TaqMan probe assays. The concentration of 25-hydroxyvitamin-D was determined by human enzyme-linked immunosorbent assay (ELISA) kits. The associations of CYP2R1 polymorphisms and risks of vitamin D deficiency (VDD) were analyzed by logistic regression. Multifactor dimensionality reduction (MDR) was used to analyze the gene-environment interaction. Multiple logistic regression was used to examine the effect of CYP2R1 gene variations, and the interaction between CYP2R1 variation and obesity on hypertension susceptibility. The results showed that rs10766197 (GG vs. AA) and rs12794714 (GG vs. AA) polymorphisms were both associated with an increased risk of VDD (OR = 1.49, 95% confidence interval (CI) = 1.08-2.05 and OR = 1.63, 95% CI = 1.19-2.25, respectively), after adjustment for potential risk factors. We also found that rs12794714 polymorphism was significantly associated with elevated risk of hypertension under the dominant model (OR = 1.26, 95% CI = 1.01-1.56). In addition, the interactions between rs12794714 with both general obesity (OR = 3.93, 95% CI = 2.72-5.68) and central obesity (OR = 3.22, 95% CI = 2.29-4.52) have significant effects on hypertension susceptibility. CONCLUSIONS: The study provided further evidence that CYP2R1 variation was associated with a higher risk of hypertension in Chinese rural population. The interaction between CYP2R1 rs12794714 and obesity may increase the risk of hypertension.

[The progress on post-exposure prophylaxis of tetanus immunological preparation in adults].

The tetanus has been eliminated in the pregnancy women and newborns in China. However, there is a gap for adult tetanus immunization, and the risk of tetanus infection cannot be ignored. In order to clearly understand the effect of the tetanus to human beings and the current use of tetanus immunological preparation for adult post-exposure prophylaxis, the incidence of the tetanus, the use status of tetanus immunological preparation and recommendations for post-exposure prophylaxis at home and abroad were reviewed and summarized, which may provide academic evidence for post-exposure prophylaxis procedures and use of tetanus immunological preparation.

[Status of HVPG clinical application in China in 2021].

Objective: The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China. Methods: This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems. Results: According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%). Conclusion: Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Myelin development in cerebral gray and white matter during adolescence and late childhood.

Myelin development during adolescence is becoming an area of growing interest in view of its potential relationship to cognition, behavior, and learning. While recent investigations suggest that both white matter (WM) and gray matter (GM) undergo protracted myelination during adolescence, quantitative relations between myelin development in WM and GM have not been previously studied. We quantitatively characterized the dependence of cortical GM, WM, and subcortical myelin density across the brain on age, gender, and puberty status during adolescence with the use of a novel macromolecular proton fraction (MPF) mapping method. Whole-brain MPF maps from a cross-sectional sample of 146 adolescents (age range 9-17 years) were collected. Myelin density was calculated from MPF values in GM and WM of all brain lobes, as well as in subcortical structures. In general, myelination of cortical GM was widespread and more significantly correlated with age than that of WM. Myelination of GM in the parietal lobe was found to have a significantly stronger age dependence than that of GM in the frontal, occipital, temporal and insular lobes. Myelination of WM in the temporal lobe had the strongest association with age as compared to WM in other lobes. Myelin density was found to be higher in males as compared to females when averaged across all cortical lobes, as well as in a bilateral subcortical region. Puberty stage was significantly correlated with myelin density in several cortical areas and in the subcortical GM. These findings point to significant differences in the trajectories of myelination of GM and WM across brain regions and suggest that cortical GM myelination plays a dominant role during adolescent development.

Caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in patients with human immunodeficiency virus infection.

OBJECTIVES: The effectiveness of trimethoprim/sulfamethoxazole (TMP/SMZ) for pneumocystis pneumonia (PCP) is limited with adverse events. Caspofungin, by inhibiting the cyst form of Pneumocystis jirovecii, may be an alternative therapy for PCP. However, the availability of clinical data about caspofungin combined with TMP/SMZ in the treatment of PCP in HIV-infected patients is limited. Thus, we aimed to examine the clinical effectiveness and safety of caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in HIV-infected patients. METHODS: From January 2017 to December 2019, data of HIV-infected patients with moderate-to-severe PCP who received either TMP/SMZ alone or caspofungin combined with TMP/SMZ as first-line therapy were retrospectively reviewed to assess the effectiveness and safety of each regimen. The Kaplan-Meier curve and log-rank test were used for survival analysis. RESULTS: A total of 278 patients met the criteria. The overall positive response rate of PCP treatment was 48.92%, and the overall all-cause in-hospital mortality rate was 33.09%. Patients who received combination therapy consisting of caspofungin and TMP/SMZ had a better positive response rate (59.44% vs. 37.78%, P < 0.001) and lower all-cause in-hospital mortality rate (24.48% vs. 42.22%, P = 0.003). Also, patients who received combination therapy had higher survival rate during a hospital stay (75.52% vs. 57.78%, P = 0.004), and those who received longer combination therapy were more likely to have higher survival rate (P = 0.042). We found that age (P = 0.019), CD4 cell count (P = 0.001) and therapeutic regimen (P = 0.002) were significant risk factors for all-cause in-hospital mortality rate in univariate analysis. In multivariate analysis, only CD4 cell count and therapeutic regimen were statistically significant factors associated with all-cause in-hospital mortality rate. Patients with a CD4 count of > 30 cells/µL and patients who received combination therapy consisting of caspofungin and TMP/SMZ were more likely to survive from PCP (P = 0.011 and P = 0.002, respectively). There were no additional severe adverse events caused by adding caspofungin. CONCLUSIONS: For HIV-infected patients with moderate-to-severe PCP, combination therapy with caspofungin and TMP/SMZ is an effective and promising first-line therapy with no greater number of adverse events compared with TMP/SMZ monotherapy. Patients who received caspofungin had better positive response rates and lower all-cause in-hospital mortality rates. Also, we recommend early initiation of caspofungin.

Linguistic effect on speech perception observed at the brainstem.

Linguistic experience affects speech perception from early infancy, as previously evidenced by behavioral and brain measures. Current research focuses on whether linguistic effects on speech perception can be observed at an earlier stage in the neural processing of speech (i.e., auditory brainstem). Brainstem responses reflect rapid, automatic, and preattentive encoding of sounds. Positive experiential effects have been reported by examining the frequency-following response (FFR) component of the complex auditory brainstem response (cABR) in response to sustained high-energy periodic portions of speech sounds (vowels and lexical tones). The current study expands the existing literature by examining the cABR onset component in response to transient and low-energy portions of speech (consonants), employing simultaneous magnetoencephalography (MEG) in addition to electroencephalography (EEG), which provide complementary source information on cABR. Utilizing a cross-cultural design, we behaviorally measured perceptual responses to consonants in native Spanish- and English-speaking adults, in addition to cABR. Brain and behavioral relations were examined. Results replicated previous behavioral differences between language groups and further showed that individual consonant perception is strongly associated with EEG-cABR onset peak latency. MEG-cABR source analysis of the onset peaks complimented the EEG-cABR results by demonstrating subcortical sources for both peaks, with no group differences in peak locations. Current results demonstrate a brainstem-perception relation and show that the effects of linguistic experience on speech perception can be observed at the brainstem level.

[Survey on present status of noise exposure of workers in metal processing industry].

Objective: To investigate the distribution of noise exposure between non-steady state noise and steady-state noise for metal processing workers, which will provide scientific basis for the prevention and treatment of noise hazards in metal processing industry. Methods: The cross-section method was used to investigate the noise exposure of 737 workers from three metal processing industries in Zhejiang Province from October to December 2017. The general demographic information and occupational history were collected by questionnaire. The noise was recorded by individual noise meters, and the noise exposure intensity (equivalent continuous A-weighted noise exposure level normalized to an 8 h-working-day, L(Aeq, 8 h)) and kurtosis were calculated. Results: Workers exposed to noise in the metal processing industry were mainly 18-40 years old (527 workers, 71.51%) , men (570 workers, 77.34%) , and junior high school education background (416 workers, 56.45%) . There were 572 workers (77.61%) with noise exposure intensity (L(Aeq, 8 h)) greater than 85 dB (A) , 558 workers (75.71%) exposed to non-steady state noise (kurtosis ≥4) , and 634 workers (86.02%) with exposure duration less than 8 years. Among the 30 work types investigated, the work types with noise intensity reaching 100% were the stamping, welding and others from a children's car manufacturing factory in Ningbo, operating, chamfering, tapping, and thread rolling from an automobile parts manufacturing factory in Ningbo; The work types with a rate of 100% exposed to non-steady state noise were the grinding from a children's car manufacturing factory in Ningbo, assembling, assembly operating and others from an automobile brake manufacturing factory in Wenzhou, and polishing from an automobile parts manufacturing factory in Ningbo. Conclusion: Metal processing workers have a high rate of over-standard exposed to high noise intensity and a high proportion exposed to non-steady state noise. It is necessary to take sound insulation and noise reduction engineering control, and strengthen personal protection and occupational health management measures to prevent and control the noise hazards.