Mental health system in China: history, recent service reform and future challenges

This paper summarizes the history of the development of Chinese mental health system; the current situation in the mental health field that China has to face in its effort to reform the system, including mental health burden, workforce and resources, as well as structural issues; the process of national mental health service reform, including how it was included into the national public health program, how it began as a training program and then became a treatment and intervention program, its unique training and capacity building model, and its outcomes and impacts; the barriers and challenges of the reform process; future suggestions for policy; and Chinese experiences as response to the international advocacy for the development of mental health.     

Aluminium bone disease in patients receiving plasma exchange with contaminated albumin.

Aluminium balance studies were carried out on eight patients with various immunological disorders who were receiving plasma exchange with albumin solutions known to be contaminated with aluminium. Four patients with impaired renal function (creatinine clearance less than 50 ml/min) retained between 60% and 74% of the aluminium infused during a single plasma exchange. Transiliac bone biopsy specimens from three patients in this group had a high content of aluminium and showed histological evidence of current or previous bone disease related to aluminium. Two of these patients suffered intermittent bone pain. The main route of excretion of injected aluminium was in urine, only a small proportion of the total input being removed in the "plasma bag" during plasma exchange. The extent of aluminium retention and bone deposition was not reflected by the plasma aluminium concentration before or after plasma exchange. Treatment of five patients with intravenous desferrioxamine increased the plasma aluminium concentration and urinary output of aluminium in those with evidence of aluminium retention. These studies show that patients with poor renal function receiving treatment with albumin contaminated with aluminium retain the metal and deposit it in bone, where it may eventually cause aluminium bone disease. Plasma exchange should be used with caution in patients with renal impairment.     

Removal of a C-terminal serine residue proximal to the inter-chain disulfide bond of a human IgG1 lambda light chain mediates enhanced antibody stability and antibody dependent cell-mediated cytotoxicity

Optimization of biophysical properties is a critical success factor for the developability of monoclonal antibodies with potential therapeutic applications. The inter-domain disulfide bond between light chain (Lc) and heavy chain (Hc) in human IgG1 lends structural support for antibody scaffold stability, optimal antigen binding, and normal Fc function. Recently, human IgG1λ has been suggested to exhibit significantly greater susceptibility to reduction of the inter Lc-Hc disulfide bond relative to the same disulfide bond in human IgG1κ. To understand the molecular basis for this observed difference in stability, the sequence and structure of human IgG1λ and human IgG1κ were compared. Based on this Lc comparison, three single mutations were made in the λ Lc proximal to the cysteine residue, which forms a disulfide bond with the Hc. We determined that deletion of S214 (dS) improved resistance of the association between Lc and Hc to thermal stress. In addition, deletion of this terminal serine from the Lc of IgG1λ provided further benefit, including an increase in stability at elevated pH, increased yield from transient transfection, and improved in vitro antibody dependent cell-mediated cytotoxicity (ADCC). These observations support the conclusion that the presence of the terminal serine of the λ Lc creates a weaker inter-chain disulfide bond between the Lc and Hc, leading to slightly reduced stability and a potential compromise in IgG1λ function. Our data from a human IgG1λ provide a basis for further investigation of the effects of deleting terminal serine from λLc on the stability and function of other human IgG1λ antibodies.     

Age-dependent choice of sexual partners and the transmission dynamics of HIV in Sub-Saharan Africa.

A mathematical model of the transmission of HIV-1 within heterosexual populations in Sub-Saharan Africa is described and its properties analysed. The model incorporates epidemiological and demographic processes and extends previous work in this area via the inclusion of age and sex dependency in rates of sexual partner change, and sexual partner choice dependent on age. Parameter assignments are made on the basis of current data on the transmission dynamics of HIV-1 and the demography of human populations in Africa. Both age-dependent rates of sexual activity and the sexual contact of males with females younger than themselves act to enhance the predicted demographic impact. With realistic parameter values, the model suggests AIDS is able to reverse the sign of population growth rates from positive to negative values over a timescale of a few decades. The sensitivity of this prediction is examined in relation to changes in the pattern of sexual contact between different age classes of females and males, different patterns of change in the age-dependent rate of sexual partner change, different assumptions concerning the doubling time of the epidemic in its early stages, and the relative efficiencies of viral transmission between men and women, and vice versa. The impact AIDS is predicted to have on the number of young and elderly persons as a fraction of the number of productive adults (the dependancy ratio) is examined under various assumptions concerning the weighting to be applied to mirror the burden imposed by the care of those with AIDS. The paper includes an assessment of the influence of the timing of changes in sexual behaviour, or the promotion of the use of condoms, on the predicted course of the epidemic. The paper concludes with a discussion of data needs and the model refinements required to more accurately mirror current understanding of the epidemiology of HIV-1.     

The S4-S5 linker acts as a signal integrator for HERG K+ channel activation and deactivation gating

Human ether-à-go-go-related gene (hERG) K(+) channels have unusual gating kinetics. Characterised by slow activation/deactivation but rapid inactivation/recovery from inactivation, the unique gating kinetics underlie the central role hERG channels play in cardiac repolarisation. The slow activation and deactivation kinetics are regulated in part by the S4-S5 linker, which couples movement of the voltage sensor domain to opening of the activation gate at the distal end of the inner helix of the pore domain. It has also been suggested that cytosolic domains may interact with the S4-S5 linker to regulate activation and deactivation kinetics. Here, we show that the solution structure of a peptide corresponding to the S4-S5 linker of hERG contains an amphipathic helix. The effects of mutations at the majority of residues in the S4-S5 linker of hERG were consistent with the previously identified role in coupling voltage sensor movement to the activation gate. However, mutations to Ser543, Tyr545, Gly546 and Ala548 had more complex phenotypes indicating that these residues are involved in additional interactions. We propose a model in which the S4-S5 linker, in addition to coupling VSD movement to the activation gate, also contributes to interactions that stabilise the closed state and a separate set of interactions that stabilise the open state. The S4-S5 linker therefore acts as a signal integrator and plays a crucial role in the slow deactivation kinetics of the channel.     

Phylogenetic relationships of the ubiquitous coral reef crab subfamily Chlorodiellinae (Decapoda,Brachyura, Xanthidae)

The xanthid subfamily Chlorodiellinae is one of the most ubiquitous coral reef crab taxa in the Indo‐West Pacific region. Many species are common in coral rubble and rocky shores from Hawaii to eastern Africa, often dominating reef cryptofauna in terms of biomass. Phylogenetic analyses of mitochondrial (COX1, 12S rRNA and 16S rRNA) and nuclear (histone H3) gene sequences of 202 specimens indicate that the Chlorodiellinae is polyphyletic as presently defined. Three genera, Pilodius, Cyclodius and Chlorodiella, and two previously undescribed lineages were recovered as a well‐supported clade. In combination with morphological data, the subfamily is redefined and restricted to this clade. Two new genera, Soliella gen. n., and Luniella gen. n., are described based on features of the carapace, male thoracic sternum and male gonopods. The remaining chlorodielline genera and members of the Etisinae, a subfamily with supposedly close morphological affinities to the Chlorodiellinae, were recovered at various positions throughout the xanthid phylogeny, although with relatively low support values. These results reiterate the unresolved status of xanthid subfamilial relationships, but nevertheless provide progress for xanthid systematics.     

Platoon Interactions and Real-World Traffic Simulation and Validation Based on the LWR-IM

Platoon based traffic flow models form the underlying theoretical framework in traffic simulation tools. They are essentially important in facilitating efficient performance calculation and evaluation in urban traffic networks. For this purpose, a new platoon-based macroscopic model called the LWR-IM has been developed in [1]. Preliminary analytical validation conducted previously has proven the feasibility of the model. In this paper, the LWR-IM is further enhanced with algorithms that describe platoon interactions in urban arterials. The LWR-IM and the proposed platoon interaction algorithms are implemented in the real-world class I and class II urban arterials. Another purpose of the work is to perform quantitative validation to investigate the validity and ability of the LWR-IM and its underlying algorithms to describe platoon interactions and simulate performance indices that closely resemble the real traffic situations. The quantitative validation of the LWR-IM is achieved by performing a two-sampled t-test on queues simulated by the LWR-IM and real queues observed at these real-world locations. The results reveal insignificant differences of simulated queues with real queues where the p-values produced concluded that the null hypothesis cannot be rejected. Thus, the quantitative validation further proved the validity of the LWR-IM and the embedded platoon interactions algorithm for the intended purpose.     

Radiation dose of digital radiography (DR) versus micro-dose x-ray (EOS) on patients with adolescent idiopathic scoliosis: 2016 SOSORT- IRSSD “John Sevastic Award” Winner in Imaging Research

Background

Patients with adolescent idiopathic scoliosis (AIS) frequently receive x-ray imaging at diagnosis and subsequent follow monitoring. The ionizing radiation exposure has accumulated through their development stage and the effect of radiation to this young vulnerable group of patients is uncertain. To achieve the ALARA (as low as reasonably achievable) concept of radiation dose in medical imaging, a slot-scanning x-ray technique by the EOS system has been adopted and the radiation dose using micro-dose protocol was compared with the standard digital radiography on patients with AIS.

Methods

Ninety-nine participants with AIS underwent micro-dose EOS and 33 underwent standard digital radiography (DR) for imaging of the whole spine. Entrance-skin dose was measured using thermoluminescent dosimeters (TLD) at three regions (i.e. dorsal sites at the level of sternal notch, nipple line, symphysis pubis). Effective dose and organ dose were calculated by simulation using PCXMC 2.0. Data from two x-ray systems were compared using independent-samples t-test and significance level at 0.05. All TLD measurements were conducted on PA projection only. Image quality was also assessed by two raters using Cobb angle measurement and a set of imaging parameters for optimization purposes.

Results

Entrance-skin dose from micro-dose EOS system was 5.9–27.0 times lower at various regions compared with standard DR. The calculated effective dose was 2.6?±?0.5 (μSv) and 67.5?±?23.3 (μSv) from micro-dose and standard DR, respectively. The reduction in the micro-dose was approximately 26 times. Organ doses at thyroid, lung and gonad regions were significantly lower in micro-dose (p?<?0.001). Data were further compared within the different gender groups. Females received significantly higher (p?<?0.001) organ dose at ovaries compared to the testes in males. Patients with AIS received approximately 16–34 times lesser organ dose from micro-dose x-ray as compared with the standard DR. There was no significant difference in overall rating of imaging quality between EOS and DR. Micro-dose protocol provided enough quality to perform consistent measurement on Cobb angle.

Conclusions

Entrance-skin dose, effective dose and organ dose were significantly reduced in micro-dose x-ray. The effective dose of a single micro-dose x-ray (2.6 μSv) was less than a day of background radiation. As AIS patients require periodic x-ray follow up for surveillance of curve progression, clinical use of micro-dose x-ray system is beneficial for these young patients to reduce the intake of ionizing radiation.