Patients with schizophrenia experiences varying clinical courses in the symptoms and up to 30-60% of patients with schizophrenia do not respond sufficiently to antipsychotics. Treatment-resistant Schizophrenia (TRS) can have several reasons, including early onset, nonadherence to oral medication regimens, and persistent negative symptoms known as deficit syndrome. Patients with TRS experience frequent exacerbations, leading to the need for higher doses of antipsychotics to achieve a clinical result.

Recently, dopamine supersensitivity psychosis (DSP) and tardive dyskinesia (TD), both of which could be caused by inappropriate pharmacotherapy, as typified by excessive dosages of antipsychotics, have also been presumed relevant to TRS. Several lines of evidence suggest that both DSP and withdrawal psychosis are closely linked to the supersensitivity of dopamine D2 receptors; this could be caused by a potent blockade of the receptors by antipsychotics. Indeed our study recently has found that patients with DSP are overlapped with the concept of treatment-resistance, and these patients can be recovered by long-acting injectable form, via amelioration of Dopamine supersensitivity state. However, it was also observed that one group did not improve at the clinical symptomatic level, despite the presence of DSP.

Here, we try to verify relation in patients with treatment-resistant schizophrenia between several classes of antipsychotics or clinical symptoms and treatment process with oral antipsychotics after the initiation of RLAI. This study is a naturalistic, one-arm design with a 12-month observation period of a moderate sample size (N=115).

Although treatment-resistant schizophrenia (TRS) is a highly heterogeneous disorder, an established and efficacious treatment for those patients to date is pharmacotherapy with clozapine. Dopamine supersensitivity psychosis (DSP) is characterized by profound unstable positive symptoms and tardive dyskinesia, and its mechanism is related to up-regulation of dopamine D2 receptors (DRD2) which can be induced by long-term treatment with antipsychotics. Patients with DSP take generally excessive high dosages of neuroleptics and thus meet easily the criteria of TRS. A drug with secure and stable pharmacokinetic, which can keep an appropriate blockade of DRD2, may contribute to amelioration and prevention of the dopamine supersensitivity state. Risperidone long-acting injection (RLAI) is a candidate agent which meets this hypothesis.

In Part 1 of this work, we have derived a dynamical system describing the approach to a finite-time singularity of the Navier–Stokes equations. We now supplement this system with an equation describing the process of vortex reconnection at the apex of a pyramid, neglecting core deformation during the reconnection process. On this basis, we compute the maximum vorticity $\unicode[STIX]{x1D714}_{max}$ as a function of vortex Reynolds number $R_{\unicode[STIX]{x1D6E4}}$ in the range $2000\leqslant R_{\unicode[STIX]{x1D6E4}}\leqslant 3400$, and deduce a compatible behaviour $\unicode[STIX]{x1D714}_{max}\sim \unicode[STIX]{x1D714}_{0}\exp [1+220(\log [R_{\unicode[STIX]{x1D6E4}}/2000])^{2}]$ as $R_{\unicode[STIX]{x1D6E4}}\rightarrow \infty$. This may be described as a physical (although not strictly mathematical) singularity, for all $R_{\unicode[STIX]{x1D6E4}}\gtrsim 4000$.

The evolution towards a finite-time singularity of the Navier–Stokes equations for flow of an incompressible fluid of kinematic viscosity $\unicode[STIX]{x1D708}$ is studied, starting from a finite-energy configuration of two vortex rings of circulation $\pm \unicode[STIX]{x1D6E4}$ and radius $R$, symmetrically placed on two planes at angles $\pm \unicode[STIX]{x1D6FC}$ to a plane of symmetry $x=0$. The minimum separation of the vortices, $2s$, and the scale of the core cross-section, $\unicode[STIX]{x1D6FF}$, are supposed to satisfy the initial inequalities $\unicode[STIX]{x1D6FF}\ll s\ll R$, and the vortex Reynolds number $R_{\unicode[STIX]{x1D6E4}}=\unicode[STIX]{x1D6E4}/\unicode[STIX]{x1D708}$ is supposed very large. It is argued that in the subsequent evolution, the behaviour near the points of closest approach of the vortices (the ‘tipping points’) is determined solely by the curvature $\unicode[STIX]{x1D705}(\unicode[STIX]{x1D70F})$ at the tipping points and by $s(\unicode[STIX]{x1D70F})$ and $\unicode[STIX]{x1D6FF}(\unicode[STIX]{x1D70F})$, where $\unicode[STIX]{x1D70F}=(\unicode[STIX]{x1D6E4}/R^{2})t$ is a dimensionless time variable. The Biot–Savart law is used to obtain analytical expressions for the rate of change of these three variables, and a nonlinear dynamical system relating them is thereby obtained. The solution shows a finite-time singularity, but the Biot–Savart law breaks down just before this singularity is realised, when $\unicode[STIX]{x1D705}s$ and $\unicode[STIX]{x1D6FF}/\!s$ become of order unity. The dynamical system admits ‘partial Leray scaling’ of just $s$ and $\unicode[STIX]{x1D705}$, and ultimately full Leray scaling of $s,\unicode[STIX]{x1D705}$ and $\unicode[STIX]{x1D6FF}$, conditions for which are obtained. The tipping point trajectories are determined; these meet at the singularity point at a finite angle. An alternative model is briefly considered, in which the initial vortices are ovoidal in shape, approximately hyperbolic near the tipping points, for which there is no restriction on the initial value of the parameter $\unicode[STIX]{x1D705}$; however, it is still the circles of curvature at the tipping points that determine the local evolution, so the same dynamical system is obtained, with breakdown again of the Biot–Savart approach just before the incipient singularity is realised. The Euler flow situation ($\unicode[STIX]{x1D708}=0$) is considered, and it is conjectured on the basis of the above dynamical system that a finite-time singularity can indeed occur in this case.

Vortex reconnection under Biot–Savart evolution is investigated geometrically and numerically using a tent model consisting of vortex filaments initially in the form of two tilted hyperbolic branches; the vortices are antiparallel at their points of nearest approach. It is shown that the tips of these vortices approach each other, accelerating as they do so to form a finite-time singularity at the apex of the tent. The minimum separation of the vortices and the maximum velocity and axial strain rate exhibit nearly self-similar Leray scaling, but the exponents of the velocity and strain rate deviate slightly from their respective self-similar values of $-1/2$ and $-1$; this deviation is associated with the appearance of distinct minima of curvature leading to cusp structures at the tips. The writhe and twist of each vortex are both zero at all times up to the instant of reconnection. By way of validation of the model, the structure of the eigenvalues and eigenvectors of the rate-of-strain tensor is investigated: it is shown that the second eigenvalue $\unicode[STIX]{x1D706}_{2}$ has dipole structure around the vortex filaments. At the tips, it is observed that $\unicode[STIX]{x1D706}_{2}$ is positive and the corresponding eigenvector is tangent to the filament, implying persistent stretching of the vortex.

The aims of this study were to show the existence of individual differences in the distribution of sperm acrosome-associated 1 (SPACA1) among male patients of infertile couples and to examine their possible impact on the outcomes of conventional in vitro fertilization (IVF). The spermatozoa were collected from male patients of infertile couples, washed by centrifugation, collected by the swim-up method, and then used for clinical treatments of conventional IVF. The surplus sperm samples were fixed and stained with an anti-SPACA1 polyclonal antibody for the immunocytochemistry. In the clinical IVF treatments, fertilization rates and blastocyst development rates were evaluated. The immunocytochemical observations revealed that SPACA1 were localized definitely in the acrosomal equatorial segment and variedly in the acrosomal principal segment. Specifically, the detection patterns of SPACA1 in the acrosomal principal segment could be classified into three categories: (A) strong, (B) intermediate or faint, and (C) almost no immunofluorescence. The SPACA1 indexes were largely different among male patients with the wide range from 13 to 199 points. The SPACA1 indexes were significantly correlated with developmental rates of embryos to blastocysts (r = 0.829, P = 0.00162), although they were barely associated with fertilization rates at 19 h after insemination (r = 0.289, P = 0.389). These results suggest that the distribution of SPACA1 in sperm affects the outcomes of conventional IVF. In conclusion, this study provides initial data to promote large-scale clinical investigation to demonstrate that the SPACA1 indexes are valid as molecular biomarkers that can predict the effectiveness of conventional IVF of infertile couples.

Based on experimental evidence that vortex reconnection commences with the approach of nearly antiparallel segments of vorticity, a linearised model is developed in which two Burgers-type vortices are driven together and stretched by an ambient irrotational strain field induced by more remote vorticity. When these Burgers vortices are exactly antiparallel, they are annihilated on the strain time-scale, independent of kinematic viscosity $\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}\nu $ in the limit $\nu \rightarrow 0$. When the vortices are skew to each other, they are annihilated under this action over a local extent that increases exponentially in the stretching direction, with clear evidence of reconnection on the same strain time-scale. The initial helicity associated with the skewed geometry is eliminated during the process of reconnection. The model applies equally to the reconnection of weak magnetic flux tubes under the action of a strain field, when Lorentz forces are negligible.

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.

The prevalence and epidemiological traits of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) infections in high-risk populations (HRPs) remained unclarified in Japan. We determined the prevalence of HIV, HBV and Treponema pallidum (TP) and the viral genotypes in HRPs who attended primary sexually transmitted infection (STI) clinics in Osaka province during 2006–2011. Of 7898 specimens, 133 (1·7%) were HIV positive, which was significantly higher than the figures reported by Japanese Red Cross (0·0019%) and public health centres (0·27%) in Japan. The frequency of HIV-1 subtype B was 88·7%, followed by CRF01_AE (2·3%) and C (0·8%), which were almost identical to the national trend. HBV seroprevalence was surprisingly high in the HIV-positive group (63·2%), which was significantly higher than that in the HIV-negative group (25·6%). By contrast, there was no statistical correlation between HIV and TP infection. Interestingly, the distinct HBV genotypes Ae and G were prevalent in the HIV-positive population (60·0% and 20·0%, respectively), although both were rarely detected during nationwide surveillance. The transmission of HIV and HBV appeared to occur largely within a closed community early in life. Of note, about one-quarter of HIV-positive cases would have remained untested if health professionals had not motivated individuals to undergo HIV testing. This is the first evidence-based assessment of HIV positivity and HIV/HBV co-infection in HRPs at primary STIs in Japan and the effect of the involvement of health professionals in the diagnosis of HIV infections in asymptomatic carriers. The genotyping of HBV provided valuable information for understanding HIV epidemical traits.

During the development of oocytes from early antral follicles (EAFs) to antral follicles (AFs), the mitochondrial DNA copy number (Mt DNA number) increases, and granulosa cells markedly proliferate. This study examined the effect of supplementation of culture medium with estradiol-17β (E2) on the in vitro growth of oocytes, and increases in the Mt DNA number, and telomere length during the in vitro culture of oocytes derived from EAFs (0.4–0.7 mm in diameter). The E2 supplementation improved antrum formation and the ratio of oocytes reaching the metaphase II (MII) stage, and there was a significant difference in these values between addition E2 concentrations of 10 μg/ml and 0.1 μg/ml. When the oocytes were cultured in the medium containing 10 μg/ml E2, the Mt DNA number determined by real-time polymerase chain reaction (PCR) significantly increased, and the ratio of the Mt DNA number at the end of culture to the Mt DNA number at the beginning of the culture was greatly different among cows, and could be predicted by the degree of the difference between the Mt DNA number of oocytes derived from EAFs and that of oocytes derived from AFs (3–6 mm in diameter). When oocytes were cultured for 16 days in a medium containing 10 μg/ml E2 or 0.1 μg/ml E2, the Mt DNA number of oocytes grown in vitro did not differ, but the telomere length of the granulosa cells was significantly greater in the 10 μg/ml E2 group than in the 0.1 μg/ml group. In conclusion, E2 supplementation in culture medium improved the growth of oocytes derived from EAFs, and a high E2 concentration increased the telomere length of the granulosa cells.

Extended abstract of a paper presented at Microscopy and Microanalysis 2010 in Portland, Oregon, USA, August 1 – August 5, 2010.

In December 2006, an outbreak of gastroenteritis occurred involving 372 guests and 72 employees at a hotel after a guest vomited in corridors on the third (F3) and 25th (F25) floors. Norovirus with identical genotype was confirmed by real-time reverse transcription–polymerase chain reaction in faecal samples from guest cases and employees. Spread of the outbreak on F25 was compared with that on F3. The attack rate in the guests who visited F25 alone (15·0%, 106/708 guests) was significantly higher than in those who visited F3 alone (3·5%, 163/4710 guests) (relative risk 4·3, 95% confidence interval 3·4–5·5, P<0·001). The outbreak on F3 ended within 2 days, while that on F25 extended over 7 days. The environmental ratios of F3 to F25 were 7·4 for volume, 6·9 for floor area and 7·6 for ventilation rate. This outbreak suggests that environmental differences can affect the propagation and persistence of a norovirus outbreak following environmental contamination.

The results are described of a transcultural psychiatric study of schizophrenia undertaken by WHO in nine countries. The study proved that such a collaboration was feasible, that it was possible to develop research procedures for international use, and that similar types of schizophrenia could be found in each of the countries involved. One thousand two hundred and two patients were studied and over 2 million items of information obtained.