We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Presentantion of the first psychotic episode of a young man and the investigation of the efficacy of treatment with olanzapine and after cariprazine.
Objectives
Assessing the response to treatment of cariprazine in a psychotic patient with relevant neuroanatomical findings.
Methods
A 25-year old man was admitted to the psychiatric intensive care due to his agggressive behavior and verbal abuse, threatening to kill them both. His medical history included long periods of negatively affected mood, social isolation and talking to himself according to his family
Results
Whent the patient was admitted he was very anxious, alert and extremely aggressive. During the interview he admitted auditory and visual hallucinations alongside delusional ideation with a particular aggression towards his father.
Upon admission his PANSS score was 121. positive scale score was 23.
The patient was treated initially with monotherapy olanzapine, gradually increased up to 20mg OD. Olanzapine caused asymptomatic transaminasemia, a relatively common adverse effect. At this point a change in medication was made and olanzapine was stopped and cariprazine was added gradually increasing its dose from 1,5mg to 6mg OD.
Interestingly the medical investigations (brain CT scan) indicated a calcification in falx cerebri.
After a period of 48 days since admission the patient was clinically improved and was discharged. His PANSS score was 72. Positive scale was 10.
Conclusions
The use of cariprazine as a treatment for a first psychotic episode of a young male improved his PANSS score after a 22-day treatment. According to the literature neuroanatomical findings have been associated with poor prognosis regarding the course of the illness. There needs to be further investigation on the efficacy of the long term treatment for this patient.
This paper investigates the effects of a light-actuated photosurfactant on the canonical problem of the linear stability of a viscous thread surrounded by a dynamically passive fluid. A model consisting of the Navier–Stokes equations and a set of molar concentration equations is presented that capture light-induced switching between two stable surfactant isomer states, trans and cis. These two states display significantly different interfacial properties, allowing for some external control of the stability behaviour of the thread via incident light. Normal modes are used to generate a generalized eigenvalue problem for the growth rate which is solved with a hybrid analytical and numerical method. The results are validated with appropriate analytical solutions of increasing complexity, beginning with a solution to a clean interface, then analytical solutions for one insoluble surfactant, one soluble surfactant and a special case of two photosurfactants with a spatially uniform undisturbed state. Presenting each of these cases allows for a holistic discussion of the effect of surfactants in general on the stability of a liquid thread. Finally, the numerical solutions in the presence of two photosurfactants that display radially non-uniform undisturbed states are presented, and details of the impact of the illumination on the linear stability of the thread are discussed.
Background :The profile of “frequent visitors” at the psychiatric emergencies (PE) has not been sufficiently investigated in Greece.
Objectives
In this study we aimed to investigate the prevalence and relevant parameters of frequent PE visits in a Greek University Psychiatric Hospital for the year 2017.
Methods
In a retrospective study, we analyzed data of patients who presented in the PE of Eginition University Hospital in Athens during 2017. Frequent visitors were grouped under this category if they had at least five visits per year. Clinical and sociodemographic data of the patients were further related to number of visits.
Results
84 patients were characterized as frequent visitors carrying out 9.8% of the total number of visits. 50% were women and 70% of them were living with family members. Anxiety, depressive and psychotic symptoms were the most frequent major complaints at the time of their visit, whereas psychosocial problems were associated with increased number of visits. Moreover, in terms of the underlying diagnosis substance use disorders significantly related to more frequent visits
Conclusions
Psychosocial problems and the diagnosis of substance use disorders significantly correlated to the number of visits at the PE of a university hospital setting in Greece for 2017.
It is known that an increased flow rate can be achieved in channel flows when smooth walls are replaced by superhydrophobic surfaces. This reduces friction and increases the flux for a given driving force. Applications include thermal management in microelectronics, where a competition between convective and conductive resistance must be accounted for in order to evaluate any advantages of these surfaces. Of particular interest is the hydrodynamic stability of the underlying basic flows, something that has been largely overlooked in the literature, but is of key relevance to applications that typically base design on steady states or apparent-slip models that approximate them. We consider the global stability problem in the case where the longitudinal grooves are periodic in the spanwise direction. The flow is driven along the grooves by either the motion of a smooth upper lid or a constant pressure gradient. In the case of smooth walls, the former problem (plane Couette flow) is linearly stable at all Reynolds numbers whereas the latter (plane Poiseuille flow) becomes unstable above a relatively large Reynolds number. When grooves are present our work shows that additional instabilities arise in both cases, with critical Reynolds numbers small enough to be achievable in applications. Generally, for lid-driven flows one unstable mode is found that becomes neutral as the Reynolds number increases, indicating that the flows are inviscidly stable. For pressure-driven flows, two modes can coexist and exchange stability depending on the channel height and slip fraction. The first mode remains unstable as the Reynolds number increases and corresponds to an unstable mode of the two-dimensional Rayleigh equation, while the second mode becomes neutrally stable at infinite Reynolds numbers. Comparisons of critical Reynolds numbers with the experimental observations for pressure-driven flows of Daniello et al. (Phys. Fluids, vol. 21, issue 8, 2009, p. 085103) are encouraging.
Partial or non-adherence to medication is high amongst patients with schizophrenia. Rates of non-adherence of up to 72% have being reported depending on the method used and the patient population. Adherence is essential for optimal long-term patient outcomes in schizophrenia and failure to adhere to medication can have a major impact on the course of illness and treatment outcomes.
Objectives
The objective of the EMEA (Europe, Middle east and Africa) ADHES survey was to collect psychiatrist's perceptions of the assessment, reasons and management of partial and non-adherence to medication.
Aims
The aim of this poster is to present psychiatrist's perceptions collected in the EMEA ADHES survey.
Methods
The survey was devised to ascertain psychiatrists’ preferred methods of assessing adherence, their perceptions of the level of adherence, reasons for non-adherence and on strategies to improve adherence.
Results
Psychiatrists estimated that during the previous month more than half of their patients (53%) were partially or non-adherent. They estimated that as few as a third of patients who deteriorated after stopping medication was able to attribute this to their non-adherence. 76% of psychiatrists assessed adherence most frequently by asking their patient explicitly. Use of long-acting treatment was the preferred choice to address adherence problems for 62% of respondents.
Discussion
This EMEA-wide survey illustrates that while respondents recognised the relevance and importance of partial and non-adherence to medication, there remains a need for more proactive management of treatment adherence of patients with schizophrenia to reduce the frequency and consequences of relapse.
Schizophrenia and bipolar disorder are both associated with increased levels of serum lipids compared to healthy controls. However, it is not clear whether patients with schizophrenia differ from bipolar patients in terms of serum lipid concentrations and hyperlipidemia rates.
Methods:
The serum lipid levels of 160 patients with schizophrenia and 41 patients with bipolar disorder (manic episode), consecutively admitted in an acute psychiatric ward during a 2-year period, were assessed.
Results:
There was no significant difference in serum cholesterol, high-density lipoproteins, low-density lipoproteins or triglycerides levels between the two groups of patients, after controlling for age. A considerable rate of schizophrenia patients demonstrated high cholesterol levels (>200mg/dl; 45.6%), whereas 15.6% of them had elevated triglyceride levels (>150 mg/dl). In bipolar patients, the rates for both
hypercholesterolemia and hypertriglyceridemia were 29.3%. The above rates did not differ significantly between the two groups of patients.
Conclusions:
Acutely hospitalized patients with schizophrenia and bipolar disorder did not differ in serum lipid concentrations and hyperlipidemia rates.
Partial or non-adherence to medication is high amongst patients with schizophrenia. Many and often overlapping factors are considered to impact on treatment adherence, including: patient-related (lack of insight, psychotic, negative or cognitive symptoms), treatment-related (adverse effects, insufficient efficacy), environmental (living situation, negative attitudes of relatives/friends), and physician-related (patient-healthcare professionals relationship) factors.
Objectives
The objective of the ADHES EMEA (Europe, Middle East and Africa) survey was to collect psychiatrist's perceptions of the assessment, reasons and management of partial and non-adherence to medication.
Aims
To present psychiatrist's opinion through EMEA of potential reasons for partial or non-adherence
Methods
The ADHES survey comprised 20 questions and was conducted in 36 countries across EMEA (over 4500 psychiatrists treating patients with schizophrenia).
Results
Across EMEA 37% of psychiatrists viewed lack of insight as the most important reason for their patients stopping medication. 23% of psychiatrists viewed patient's feeling better and thinking it unnecessary to take medication as the most important reason for their patients stopping medication. 7% or less of psychiatrists viewed undesirable side effects, insufficient efficacy, cognitive impairment or drug/alcohol abuse as the most important reasons for their patients stopping medication.
Discussion
In this survey, psychiatrists estimated that patient’s lack of insight and subjective improvement could constitute the main factors explaining poor adherence. Other factors (i.e., side effects, substance abuse) were regarded as less important. Strategies aimed at raising awareness of maintaining treatment, are warranted within EMEA, with the aim of improving clinical outcomes.
Rates of non-adherence of up to 72% have being reported, in schizophrenia, depending on the method used and the patient population. Rates of approximately 59% over 1 year have been reported for individuals with a first episode. Patients who stop medication are almost five times more likely to experience relapse than adherent patients. Failure to adhere to medication can have a major impact on the course of illness and treatment outcomes.
Objectives
The EMEA (Europe, Middle East and Africa) ADHES schizophrenia survey was a survey of psychiatrists across the region, treating patients with schizophrenia, designed to canvas their perceptions of assessment, potential reasons and management for partial or non-adherence to medication amongst their patients.
Aims
To present methodology and demographics of the EMEA ADHES survey in schizophrenia.
Methods
The EMEA ADHES survey comprised 20 questions and was conducted in 36 countries across EMEA. In addition to recording the gender, age and practice setting of the respondents, questions related directly to the issue of partial-/non-adherence in patients with schizophrenia.
Results
The survey was conducted amongst psychiatrists (including neurologists with psychiatric background in Germany) from January - March 2010. Results were obtained from 4722 respondents. Psychiatrists perceived that during the previous month more than half of their patients (53%) were partially or non-adherent across all EMEA regions
Discussion
The EMEA ADHES schizophrenia survey is a large and geographically broad survey providing insight on psychiatrists’ perceptions of the assessment, causes and management of partial and non-adherence to medication.
Zolpidem is a GABA (A) agonist, which is indicated for the short-term management of insomnia. Recent research provide evidence suggesting that zolpidem produces spatial working memory (WM) deficits and dependence; however, the underlying mechanisms of these effects are unknown. Since the auditory N400 component of event-related potentials (ERPS) is considered as an index of memory use of context processing, the present study focused on N400 waveform of ERPs elicited during a WM task in a case suffering from zolpidem dependence. The patterns of N400 waveform of this case were compared to the patterns obtained from healthy controls. This comparison revealed that zolpidem dependence is accompanied by reduced amplitudes located at posterior brain areas and diffuse prolongation of N400. These findings may indicate that zolpidem dependence manifests alterations with regard to the memory use of context processing, involving or affecting a wide-ranging network of the brain's structures.
Many association studies have reported associations between the brain-derived neurotrophic factor (BDNF) gene and psychiatric disorders including major depression (MDD). the BDNF gene has further been associated with suicidal behaviour, as well as with treatment response, although with conflicting results. in the present study, we further elucidate the impact of BDNF in MDD patients with suicide risk and/or a personal history of suicide attempts.
Two hundred fifty MDD patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using Mini International Neuropsychiatric Interview (MINI) and Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for eight SNPs within the BDNF gene.
With regard to suicide risk and personal history of suicide attempts, neither single marker nor haplotypic association was found with any SNP after multiple testing correction. However, in gender-specific analyses, we found haplotypic association with suicide risk in males, but not in females (rs925946-rs10501087-rs6265, rs10501087-rs6265-rs122733). the only single-marker association with suicide risk in males (rs908867) did not resist multiple testing correction. No significant associations were found in gender-specific analyses with regard to a personal history of suicide attempts.
In conclusion, we found two BDNF haplotypes significantly associated with suicide risk in male MDD patients. However, replication in larger well-defined cohorts is required to dissect this further.
Partial/non-adherence to medication is common amongst patients with schizophrenia. Nurses play an important role in assessing and managing mental health problems and are often involved in helping patients manage and adhere to their medication. As such, the perception of nurses regarding the burden and potential causes of non-adherence is vital in addressing the adherence problem.
Objectives
The ADHES nurses survey collected opinions of nurses across the EMEA (Europe, Middle East and Africa) region.
Aim
To ascertain nurses' perceptions of assessment, potential causes and management of partial/non-adherence to medication in patients with schizophrenia.
Methods
The survey was conducted from January-March 2010 in 29 countries across EMEA, comprising 14 questions addressing the issue of partial/non-adherence and the use of long-acting injectable (LAI) antipsychotic medication in patients with schizophrenia.
Results
Results were obtained from 4120 respondents. Nurses estimated high levels of partial/non-adherence (mean 54%) amongst patients with schizophrenia and 85% believed improving medication adherence would have a huge/sizable impact on patient outcomes. 93% believed that continuous medication with an LAI would have long-term benefits for patients with schizophrenia, and that many patients (mean 40%) would prefer LAI medication.
Conclusion
Nurses recognize the issue of partial/non-adherence to medication in patients with schizophrenia. Most nurses believe patients are well informed about LAI antipsychotics, however, approximately a third of nurses believe patients to be poorly informed. There is a need to address the problem of partial/non-adherence in clinical practice with a multidisciplinary approach to avoid suboptimal treatment outcomes in patients with schizophrenia.
Cyclothymic-depressive-anxious-irritable (CDAI) temperament has been linked to increased suicidal risk. Sleep disturbance and short self-reported sleep duration have been associated with suicidal ideation and behavior independently of a current major depressive episode (MDE).
Objectives
This cross-sectional study in consecutive hospitalized suicide attempters aimed to investigate the interplay of temperament with proximal sleep disturbance in predicting suicide intent.
Methods
Depression severity was measured with Major Depression Inventory, whereby DSM-IV-TR diagnosis of current MDE was derived. Temporally proximal sleep disturbance (during ≥2 weeks preceding the attempt) was assessed with Athens Insomnia Scale (AIS); average night sleep duration (ANSD) was also self-reported. Suicidal intent was recorded with Beck's Suicide Intent Scale (BSIS). Attempters’ temperament profile was investigated with TEMPS-A self-report questionnaire. A two-step cluster analysis of TEMPS-A subscales mean scores was performed. BSIS was sequentially regressed on AIS and ANSD along with their interactions with temperament clusters after adjusting for clinicodemographic variables and current MDE.
Results
114 subjects (57.9% females), aged 16-87 (44.1±17.7) years were included. 50% reported previous attempts. 38.6% were currently depressed. 62.3% suffered from insomnia (AIS score ≥6); 42.1% slept ≤5 hours per night on average. Cluster analysis identified a CDAI group and a non-CDAI one. In multiple regressions, BSIS was independently associated with current MDE, CDAI temperament profile, AIS (beta=0.43, p=0.004) and ANSD (beta=-0.40, p=0.002). Significant interactions of temperament cluster with AIS (p=0.017) and ANSD (p=0.011) were recorded.
Conclusions
Temperament profile interacts with proximal insomnia and short self-reported sleep duration in predicting suicidal intent in recent attempters.
Seasonal affective disorder (SAD) is a subtype of recurrent depressive or bipolar disorder that is characterized by regular onset and remission of affective episodes at the same time of the year. The aim of the present study was to provide epidemiological data and data on the socioeconomic impact of SAD in the general population of Austria.
Methods
We conducted a computer-assisted telephone interview in 910 randomly selected subjects (577 females and 333 males) using the Seasonal Health Questionnaire (SHQ), the Seasonal Pattern Assessment Questionnaire (SPAQ), and the Sheehan Disability Scale (SDS). Telephone numbers were randomly drawn from all Austrian telephone books and transformed using the random last digits method. The last birthday method was employed to choose the target person for the interviews.
Results
Out of our subjects, 2.5% fulfilled criteria for the seasonal pattern specifier according to DSM-5 and 2.4% (95% CI = 1.4–3.5%) were diagnosed with SAD. When applying the ICD-10 criteria 1.9% (95% CI = 0.9–2.8%) fulfilled SAD diagnostic criteria. The prevalence of fall-winter depression according to the Kasper-Rosenthal criteria was determined to be 3.5%. The criteria was fulfilled by 15.1% for subsyndromal SAD (s-SAD). We did not find any statistically significant gender differences in prevalence rates. When using the DSM-5 as a gold standard for the diagnosis of SAD, diagnosis derived from the SPAQ yielded a sensitivity of 31.8% and a specificity of 97.2%. Subjects with SAD had significantly higher scores on the SDS and higher rates of sick leave and days with reduced productivity than healthy subjects.
Conclusions
Prevalence estimates for SAD with the SHQ are lower than with the SPAQ. Our data are indicative of the substantial burden of disease and the socioeconomic impact of SAD. This epidemiological data shows a lack of gender differences in SAD prevalence. The higher rates of females in clinical SAD samples might, at least in part, be explained by lower help seeking behaviour in males.
Malnutrition risk screening in cirrhotic patients is crucial, as poor nutritional status negatively affects disease prognosis and survival. Given that a variety of malnutrition screening tools is usually used in routine clinical practice, the effectiveness of eight screening tools in detecting malnutrition risk in cirrhotic patients was sought. A total of 170 patients (57·1 % male, 59·4 (sd 10·5) years, 50·6 % decompensated ones) with cirrhosis of various aetiologies were enrolled. Nutritional screening was performed using the Malnutrition Universal Screening Tool, Nutritional Risk Index, Malnutrition Screening Tool, Nutritional Risk Screening (NRS-2002), Birmingham Nutritional Risk Score, Short Nutritional Assessment Questionnaire, Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT) and Liver Disease Undernutrition Screening Tool (LDUST). Malnutrition diagnosis was defined using the Subjective Global Assessment (SGA). Data on 1-year survival were available for 145 patients. The prevalence of malnutrition risk varied according to the screening tools used, with a range of 13·5–54·1 %. RFH-NPT and LDUST were the most accurate in detecting malnutrition (AUC = 0·885 and 0·892, respectively) with a high sensitivity (97·4 and 94·9 %, respectively) and fair specificity (73·3 and 58 %, respectively). Malnutrition according to SGA was an independent prognostic factor of within 1-year mortality (relative risk was 2·17 (95 % CI 1·0, 4·7), P = 0·049) after adjustment for sex, age, disease aetiology and Model for End-stage Liver Disease score, whereas nutrition risk according to RFH-NPT, LDUST and NRS-2002 showed no association. RFH-NPT and LDUST were the only screening tools that proved to be accurate in detecting malnutrition in cirrhotic patients.
Lifestyle interventions remain the cornerstone therapy for non-alcoholic fatty liver disease (NAFLD). This randomised controlled single-blind clinical trial investigated the effect of Mediterranean diet (MD) or Mediterranean lifestyle, along with weight loss, in NAFLD patients. In all, sixty-three overweight/obese patients (50 (sd 11) years, BMI=31·8 (sd 4·5) kg/m2, 68 % men) with ultrasonography-proven NAFLD (and elevated alanine aminotransferase (ALT) and/or γ-glutamyl transpeptidase (GGT) levels) were randomised to the following groups: (A) control group (CG), (B) Mediterranean diet group (MDG) or (C) Mediterranean lifestyle group (MLG). Participants of MDG and MLG attended seven 60-min group sessions for 6 months, aiming at weight loss and increasing adherence to MD. In the MLG, additional guidance for increasing physical activity and improving sleep habits were given. Patients in CG received only written information for a healthy lifestyle. At the end of 6 months, 88·8 % of participants completed the study. On the basis of intention-to-treat analysis, both MDG and MLG showed greater weight reduction and higher adherence to MD compared with the CG (all P<0·05) at the end of intervention. In addition, MLG increased vigorous exercise compared with the other two study groups (P<0·001) and mid-day rest/naps compared with CG (P=0·04). MLG showed significant improvements in ALT levels (i.e. ALT<40 U/l (P=0·03) and 50 % reduction of ALT levels (P=0·009)) and liver stiffness (P=0·004) compared with CG after adjusting for % weight loss and baseline values. MDG improved only liver stiffness compared with CG (P<0·001) after adjusting for the aforementioned variables. Small changes towards the Mediterranean lifestyle, along with weight loss, can be a treatment option for patients with NAFLD.
The nonlinear stability of viscous, immiscible multilayer flows in plane channels driven both by a pressure gradient and gravity is studied. Three fluid phases are present with two interfaces. Weakly nonlinear models of coupled evolution equations for the interfacial positions are derived and studied for inertialess, stably stratified flows in channels at small inclination angles. Interfacial tension is demoted and high-wavenumber stabilisation enters due to density stratification through second-order dissipation terms rather than the fourth-order ones found for strong interfacial tension. An asymptotic analysis is carried out to demonstrate how these models arise. The governing equations are $2\times 2$ systems of second-order semi-linear parabolic partial differential equations (PDEs) that can exhibit inertialess instabilities due to interaction between the interfaces. Mathematically this takes place due to a transition of the nonlinear flux function from hyperbolic to elliptic behaviour. The concept of hyperbolic invariant regions, found in nonlinear parabolic systems, is used to analyse this inertialess mechanism and to derive a transition criterion to predict the large-time nonlinear state of the system. The criterion is shown to predict nonlinear stability or instability of flows that are stable initially, i.e. the initial nonlinear fluxes are hyperbolic. Stability requires the hyperbolicity to persist at large times, whereas instability sets in when ellipticity is encountered as the system evolves. In the former case the solution decays asymptotically to its uniform base state, while in the latter case nonlinear travelling waves can emerge that could not be predicted by a linear stability analysis. The nonlinear analysis predicts threshold initial disturbances above which instability emerges.
We consider the full three-dimensional dynamics of a thin falling liquid film on a flat plate inclined at some non-zero angle to the horizontal. In addition to gravitational effects, the flow is driven by an electric field which is normal to the substrate far from the flow. This extends the work of Tseluiko & Papageorgiou (J. Fluid Mech., vol. 556, 2006b, pp. 361–386) by including transverse dynamics. We study both the cases of overlying and hanging films, where the liquid lies above or below the substrate, respectively. Starting with the Navier–Stokes equations coupled with electrostatics, a fully nonlinear two-dimensional Benney equation for the interfacial dynamics is derived, valid for waves that are long compared to the film thickness. The weakly nonlinear evolution is governed by a Kuramoto–Sivashinsky equation with a non-local term due to the electric field effect. The electric field term is linearly destabilising and produces growth rates proportional to $|\unicode[STIX]{x1D743}|^{3}$, where $\unicode[STIX]{x1D743}$ is the wavenumber vector of the perturbations. It is found that transverse gravitational instabilities are always present for hanging films, and this leads to unboundedness of nonlinear solutions even in the absence of electric fields – this is due to the anisotropy of the nonlinearity. For overlying films and a restriction on the strength of the electric field, the equation is well-posed in the sense that it possesses bounded solutions. This two-dimensional equation is studied numerically for the case of periodic boundary conditions in order to assess the effects of inertia, electric field strength and the size of the periodic domain. Rich dynamical behaviours are observed and reported. For subcritical Reynolds number flows, a sufficiently strong electric field can promote non-trivial dynamics for some choices of domain size, leading to fully two-dimensional evolutions of the interface. We also observe two-dimensional spatiotemporal chaos on sufficiently large domains. For supercritical flows, such two-dimensional chaotic dynamics emerges in the absence of a field, and its presence enhances the amplitude of the fluctuations and broadens their spectrum.
We present a model for ice formation in a thin, viscous liquid film driven by a Blasius boundary layer after heating is switched off along part of the flat plate. The flow is assumed to initially be in the Nelson et al. (J. Fluid Mech., vol. 284, 1995, pp. 159–169) steady-state configuration with a constant flux of liquid supplied at the tip of the plate, so that the film thickness grows like $x^{1/4}$ in distance along the plate. Plate cooling is applied downstream of a point, $Lx_{0}$, an $O(L)$-distance from the tip of the plate, where $L$ is much larger than the film thickness. The cooling is assumed to be slow enough that the flow is quasi-steady. We present a thorough asymptotic derivation of the governing equations from the incompressible Navier–Stokes equations in each fluid and the corresponding Stefan problem for ice growth. The problem breaks down into two temporal regimes corresponding to the relative size of the temperature difference across the ice, which are analysed in detail asymptotically and numerically. In each regime, two distinct spatial regions arise, an outer region of the length scale of the plate, and an inner region close to $x_{0}$ in which the film and air are driven over the growing ice layer. Moreover, in the early time regime, there is an additional intermediate region in which the air–water interface propagates a slope discontinuity downstream due to the sudden onset of the ice at the switch-off point. For each regime, we present ice profiles and growth rates, and show that for large times, the film is predicted to rupture in the outer region when the slope discontinuity becomes sufficiently enhanced.
DNA methylation is an epigenetic marker that has been shown to vary significantly across different tissues. Taking advantage of the methylation differences between placenta-derived cell-free DNA and maternal blood, several groups employed different approaches for the discovery of fetal-specific biomarkers. The aim of this study was to analyse whole-genome fetal and maternal methylomes in order to identify and confirm the presence of differentially methylated regions (DMRs). We have initially utilized methylated DNA immunoprecipitation (MeDIP) and next-generation sequencing (NGS) to identify genome-wide DMRs between chorionic villus sampling (CVS) and female non-pregnant plasma (PL) and peripheral blood (WBF) samples. Next, using specific criteria, 331 fetal-specific DMRs were selected and confirmed in eight CVS, eight WBF and eight PL samples by combining MeDIP and in-solution targeted enrichment followed by NGS. Results showed higher enrichment in CVS samples as compared to both WBF and PL samples, confirming the distinct methylation levels between fetal and maternal DNA for the selected DMRs. We have successfully implemented a novel approach for the discovery and confirmation of a significant number of fetal-specific DMRs by combining for the first time MeDIP and in-solution targeted enrichment followed by NGS. The implementation of this double-enrichment approach is highly efficient and enables the detailed analysis of multiple DMRs by targeted NGS. Also, this is, to our knowledge, the first reported application of MeDIP on plasma samples, which leverages the implementation of our enrichment methodology in the detection of fetal abnormalities in maternal plasma.