Proactive Investigation Research Articles

Lessons from Post-Immunotherapy Tumor Tissues in Clinical Trials: How Can We Fuel the Tumor Microenvironment in Gliomas?

Despite recent advancements in cancer immunotherapy, many patients with gliomas and glioblastomas have yet to experience substantial therapeutic benefits. Modulating the tumor microenvironment (TME) of gliomas, which is typically "cold", is crucial for improving treatment outcomes. Clinical tumor specimens obtained post-immunotherapy provide invaluable insights. However, access to such post-immunotherapy samples remains limited, even in clinical trials, as tumor tissues are often collected only at tumor relapse. Recent studies of neoadjuvant immunotherapy provided important insights by incorporating surgical resections of post-treatment tumors. Moreover, pre-surgical immunotherapies are increasingly integrated into clinical trial designs to evaluate treatment efficacy. These investigations reveal critical information, particularly regarding the delivery success of therapeutic agents, the expansion and persistence of immune products, and the cellular and molecular changes induced in the TME. In this review, we assess the findings on post-treatment tumor specimens obtained from recent immunotherapy clinical trials on gliomas, highlight the importance of these samples for understanding therapeutic impacts, and discuss proactive investigation approaches for future clinical trials.

Targeting the CDK7-MDK axis to suppresses irinotecan resistance in colorectal cancer

AimsColorectal cancer (CRC) remains a major global health issue, with metastatic cases presenting poor prognosis despite advances in chemotherapy and targeted therapy. Irinotecan, a key drug for advanced CRC treatment, faces challenges owing to the development of resistance. This study aimed to understand the mechanisms underlying irinotecan resistance in colorectal cancer. Main methodsWe created a cell line resistant to irinotecan using HT29 cells. These resistant cells were utilized to investigate the role of the CDK7-MDK axis. We employed bulk RNA sequencing, conducted in vivo experiments with mice, and analyzed patient tissues to examine the effects of the CDK7-MDK axis on the cellular response to irinotecan. Key findingsOur findings revealed that HT29 cells resistant to irinotecan, a crucial colorectal cancer medication, exhibited significant phenotypic and molecular alterations compared to their parental counterparts, including elevated stem cell characteristics and increased levels of cytokines and drug resistance proteins. Notably, CDK7 expression was substantially higher in these resistant cells, and targeting CDK7 effectively decreased their survival and tumor growth, enhancing irinotecan sensitivity. RNA-seq analysis indicated that suppression of CDK7 in irinotecan-resistant HT29 cells significantly reduced Midkine (MDK) expression. Decreased CDK7 and MDK levels, achieved through siRNA and the CDK7 inhibitor THZ1, enhanced the sensitivity of resistant HT29 cells to irinotecan. SignificanceOur study sheds light on how CDK7 and MDK influence irinotecan resistance in colorectal and highlights the potential of MDK-targeted therapies. We hypothesized that irinotecan sensitivity and overall treatment efficacy would improve by inhibiting MDK. This finding encourages a careful yet proactive investigation of MDK as a therapeutic target to enhance outcomes in colorectal cancer patients.

THE CHECHNYA CASES AS AN ILLUSTRATION OF THE WAY THE EUROPEAN COURT INTERPRETED THE PROCEDURAL OBLIGATION UNDER ARTICLE 2 OF THE EUROPEAN CONVENTION ON HUMAN RIGHTS

This paper explores the European Court of Human Rights’ procedural obligations under Article 2 through the lens of three pivotal Chechnya conflict cases. It underscores the Court’s insistence on comprehensive investigations into forcerelated deaths, emphasizing accountability and proactive investigation initiation by state authorities. Highlighted cases illustrate systemic investigation failures, including premature closure, lack of thorough victim and witness identification, and procedural neglect. The paper critiques delayed and inadequate investigation efforts, underscoring the Court’s evolving jurisprudence towards more detailed investigative obligations under Article 2, reflecting a balance between upholding the right to life and addressing states’ operational challenges.

Sleep quality and sleep disorders in patients with acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Sleep disorders have been considered risk factors for cardiovascular diseases, and poor sleep quality has become a common complaint in patients with coronary artery disease. Despite being a very common problem in these patients, it is not yet routinary studied and reflected in the clinical practice guidelines. Purpose To study the prevalence and type of sleep disorders in patients with acute coronary syndrome (ACS). Methods This study was a quantitative, descriptive, cross-sectional investigation. We included patients admitted for ACS (unstable angina, STEMI, NSTEMI, MINOCA,...) during the period from June to October 2022. The patients were interviewed, collecting the following information: Demographic variables (age, sex, marital status), classic cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidemia), presence or absence of a diagnosis of Obstructive Sleep Apnoea (OSA), as well as treatment or not with CPAP, toxic habits (tobacco, alcohol, other drugs), need for sleep medication and sleep quality using the Pittsburgh Sleep Quality Index (PSQI), which is a validated self-rated questionnaire that assesses sleep quality and sleeps disturbance over the past month. Results We included 46 patients in our study. The mean age was 68,85 years (SD 11,88), 69,56% were male and 60,87% were married. The main reason for admission was NSTEMI. The distribution of risk factors was: High blood pressure 78,26%, Diabetes Mellitus 36,96%, dyslipidemia 63,04%, smoking 21,74%, drinking alcohol habitually 19,57%, and other drugs abuse 4,35%. The prevalence of OSA was 17,39%. Overall, the mean PSQI score of all participants was 8,98 (SD 4,73). The most affected sleep component was ‘Sleep disturbance’ (mean score 1,76/3), followed by ‘Sleep latency’ (1,5/3) and ‘Sleep duration’ (1,48/3). 34,78 % referred use of sleep medication and 41,30% had daytime dysfunction. Table 1 shows the results in PSQI related to the reason for hospitalization. Conclusions Sleep disorders and poor sleep quality are remarkably prevalent in our cohort of ACS patients, which could be considered as a possible added cardiovascular risk factor or risk modifier. We consider the proactive investigation of sleep disorders useful in clinical practice as we can develop strategies to improve sleep and reduce residual cardiovascular risk and quality of life.

The necessity of a modern approach to criminal investigation of organized crime

Since organized and other forms of crime are liable to change, modernisation and adaptation to specific social conditions, this phenomenon also requires some changes, but this time in the approach used in its detection, prevention, or proof. The primary reason for the selection of this topic is to draw the attention of the scientific society to the importance of expanding existing scientific and professional knowledge in the field of the criminal investigation of organized crime. Continuous and accelerated development of organized crime should be accompanied by the simultaneous development and improvement of tactical approaches to the investigation of this socially negative phenomenon. This article is primarily aimed at pointing out the importance of continuous improvement of traditional, classical, or methods in use, but also the development of new and modern activities that are used to combat organized crime. In addition to the conceptual definition and presentation of the elements that characterise organized crime, the author emphasises the importance of modernisation or improvement of the traditional investigation approach and presents a significant contemporary approach in the criminal investigation of organized crime. There is no success and progress in combating organized crime without proactive investigation, modern technologies, intelligence gathering, and special investigative measures. It should be noted that organized crime in most cases expands its activities to two or more countries, i.e., achieves cross-border activities that require international cooperation (criminal, police, inter-agency). The value of international police cooperation is also reflected in the fact that organized crime operates across national boundaries, does not choose society or state. Accordingly, it would be much more effective for judicial, police, and other competent authorities to remove any kind of obstacles, barriers and raise up international co-operation to the highest level, to establish an effective system for combating organized crime.

“So, Sue Me:” Medical Professionals Should Support Title VI Civil Rights Law Improvements as Part of their Anti-racism Work

“So, Sue Me:” Medical Professionals Should Support Title VI Civil Rights Law Improvements as Part of their Anti-racism Work

The theory and evidence behind law enforcement strategies that combat child sexual abuse material

This article presents a synthesis of current and innovative law enforcement strategies to combat child sexual abuse material. Six law enforcement strategies were identified through an international literature search and verified by experts via roundtable discussion. Six strategies were identified: public intelligence gathering, polygraph, proactive investigations, risk assessment prioritization, resourced taskforces and collaborative partnerships. Strategies are reported via an adapted version of the ‘EMMIE’ framework: effects, mechanisms, moderators, and implementation considerations. Through applying the adapted framework, this article explains how and why each law enforcement strategy may work, and identifies the factors that may impact each strategy’s success. As a result, this article offers a valuable resource for practice professionals across the globe. The synthesis does not include an assessment of whether prior evidence supports the strategies discussed.

Citizen Led Policing in the Digital Realm: Paedophile Hunters and Article 8 in the case of Sutherland v Her Majesty's Advocate

AbstractIn Sutherland v Her Majesty's Advocate, the Supreme Court unanimously dismissed an appeal which argued that the use of communications obtained by a paedophile hunter group as evidence in criminal prosecution was a violation of Article 8 of the European Convention on Human Rights. The case raises fundamental questions of the scope of the right to private life as regards to the content of communications and the role played by private actors in the criminal justice process. This note argues that by limiting the protection of Article 8 to private communications which satisfy a contents‐based test, the Court has bypassed the Article 8(2) balancing test to the detriment of the due process rights of the accused. The note concludes that the decision opens up the prospect of the state circumventing the accused's Article 8 privacy rights by lending tacit approval to the proactive investigations of these private ‘paedophile hunter’ groups.

GC–MS and GC–IR analysis of methylenedioxyphenylalkylamine analogues of the psychoactive 25X-NBOMe drugs

Twelve secondary amines representing structural analogues of the classic NBOMe category of novel psychoactive substances were prepared and evaluated in GC-EI-MS and vapor phase GC–IR studies. These compounds all contain the methylenedioxy group fused with the aromatic ring of the phenethyl moiety in the classic NBOMe chemical framework. One subseries of analogues, the three regioisomeric phenylisopropylamines, can be viewed as the N-methoxybenzyl analogues of 3,4-methylenedioxyamphetamine (MDA). Another subseries of three regioisomers contains the bromine and two methoxy groups at positions 2, 4 and 5 of the benzyl side of the molecule. The GC properties and the correlated EI-MS fragmentation products of these amines and some trifluoroacetamide derivatives were evaluated and compared to the traditional drug of abuse 25B-NBOMe. The compounds in this study are not currently known drugs of abuse and this proactive investigation provides data for differentiation of these analogues from the current NBOMe drugs of abuse. The observed GC elution order for the regioisomeric methoxybenzyl analogues on an Rxi®-17Sil MS phase was the 2-methoxy isomer eluting before the 3-substituted isomer, and the 4-substituted isomer eluting last. A similar comparison for the position of methylenedioxy fusion shows the 2,3-substituted isomer eluted before the 3,4-substituted isomer. All these secondary amines undergo EI fragmentation yielding the iminium cation via C–C bond cleavage of the phenethyl chain and the two benzylic cationic species. The mass spectra for the trifluoroacetyl derivatives in the bromodimethoxybenzyl substituted subseries provided additional structural information based on unique fragmentation processes. These characteristic ions are formed following initial hydrogen rearrangement within the molecular radical cation. The vapor phase infrared (vpIR) spectra confirm the position of substitution of the methylenedioxy, methoxy and bromodimethoxy groups.

Applying Spatio-temporal Analysis in Telecom Fraud Investigation

Recently telecom fraud has become a severe problem worldwide, resulting in billions of dollars each year. To prevent telecom fraud, Taiwan National Police Agency proposes an Anti-money Mule Project to detect and arrest mules responsible for withdrawing victims’ ATM cash from telecom fraud. This study used the Python program to integrate visual data for the following three significant phases: time series, spatial connection, and geographic map data. These phases can analyze 2,238 remittance accounts that were withdrawn transaction records by the money mules. Our research results have demonstrated that Spatio-temporal analysis could help investigators linkage transaction records by the same money mule, narrow down the scope of the investigation, and increase the possibility of finding out the suspect. The Spatio-temporal analysis is successfully applied as a systematic, proactive investigation technique in Taiwan’s telecom fraud investigation.

Discrimination in the complaints process: introducing the sector guidance to address staff sexual misconduct in UK higher education

ABSTRACT This article introduces our Sector Guidance to Address Staff Sexual Misconduct in UK Higher Education. The problem that the guidance seeks to address is that existing student complaints and staff disciplinary procedures relating to student complaints in this area fail to offer similar protections and privileges to the student complainant and the responding staff member and, as a result, students are often excluded from the process purporting to resolve their complaint. We outline the changes that would need to be made to staff disciplinary processes to follow a process more akin to civil justice than criminal justice, thus ensuring that the process accords equal rights to complainants and respondents. The article highlights points of discussion that came up in the consultation process to devise the guidance, including sharing outcomes with complainants, recording data on disclosures as well as formal reports, and proactive investigations in the absence of formal reports.

Uninvestigated fatal workplace injuries in the United States

Approximately 5000 people are killed by an injury at work every year, but the U.S. Occupational Safety and Health Administration (OSHA) only investigates 25%-35% of these deaths. The aim of this study was to identify industry, geographic, and worker demographic disparities in the proportion of fatal workplace injuries that are investigated by OSHA. This cross-sectional analysis drew from 2 years of public data (2014-2015) from the Census of Fatal Occupational Injuries and investigation data from OSHA. Differences by worker age and sex, geographic region, industry, and State Plan- versus Federal Plan-state were examined. Nationally, OSHA investigated about one in four (27.5%) of the 9657 fatal workplace injuries that occurred. Higher odds of uninvestigated fatalities were observed for female workers compared to male workers (odds ratio, 2.35; 95% confidence interval, 1.89, 2.93), for workers over age 65 compared to those aged 18-24 (3.05; 2.44, 3.82), for worker deaths occurring in State Plan states compared to Federal Plan states (1.64; 1.49, 1.79), among other differences. Although some of the disparities could be explained by OSHA jurisdiction restrictions, other areas of potential reform were identified, such as investigating a greater number of workplace violence deaths and increasing focus in industries with a low proportion of investigations but a high number of fatalities, such as transportation and warehousing. Consideration should be given to adapt policies, expand OSHA jurisdiction, and to increase OSHA resources for conducting both fatality investigations and proactive investigations that can identify and abate hazards before a worker is injured.

A contribution to defining of integrity testing in police: Crime-investigating aspects

The shortcomings of reactive approach to suppression of corruption in police, as well as in other spheres of so-called consensual and victimless crime required introduction of proactive investigations and relying on covert methods of work. New crime-investigating strategy relies largely on building of professional integrity, as well as its testing, including integrity testing. This is a specific mode of simulated investigating methods which should show if the police officers in certain simulated situations are corrupt or prone to commission of other crimes, misusing their position and status. Although hypothetically any member of the police can be tested, the tendency is to do targeted testing, in other words to test those who are suspected of being criminalized. Considering that integrity testing is essentialy simulated deal/activity, in which the subject is put into a simulated environment in order to see if he will commit an indictable act, it is important in its implementation to take care of encouraging, or acting in the role of agent provocateur.

Investigation and Prosecution of Terrorism Under the Terrorism (Prevention) (Amendment) Act, 2013

Terrorism despite being a global phenomenon has remained a subject matter that resisted social scientists efforts in proffering an acceptable definition. The rise of the dreaded Islamist group “Boko Haram” formally known as Jama’tu Ahlis Sunna Lidda’awati wal-Jihad, in 2009, changed the dynamics of terrorism in Nigeria. This amongst the activities of other persons and group propelled the Nigerian Government to enacting the Terrorism (Prevention) Act, 2011. This piece of legislation was amended in 2013 as Terrorism (Prevention) (Amendment) Act, 2013. The Work proceeds in five unequal parts. The work took a look at investigations and prosecution of terrorism offences under the Terrorism (Prevention) (Amendment) Act, 2013. It considers reactive and proactive investigation. Acts that constitute terrorism acts are highlighted with discussion of issues that arises in pre-trial and trial of terrorism offences. The roles of the National Security Adviser and the Attorney-General of the Federation in Prosecuting Offences of Terrorism are highlighted in this work, even as a clarion call is made for synergy and cooperation between the office of the National Security Adviser and the Attorney-General of the Federation in ensuring effective investigation and prosecution of terrorism offences. Capacity building of all state actors (Security and law enforcement agencies) must be vigorously pursued.

Issues in Underwater Cultural Heritage Impact Assessments in China

During the past decades, the number of coastal and marine construction projects has multiplied in China, posing a serious threat to underwater cultural heritage in its waters. In contrast, there are few rules dealing with underwater cultural heritage impact assessment which has not yet become a mandatory procedure in various coastal and marine construction projects. With China putting forward the Belt and Road Initiative, the conflicts between the protection of underwater cultural heritage and the need of various coastal and marine construction projects might become more frequent. Chinese legislation in this domain, undergoing important revision, intends to establish a mandatory procedure of proactive archeological investigation. This revision could have a great influence on the protection of underwater cultural heritage as well as the coastal and marine construction projects in China but the relevant provisions are still far from satisfactory. The present study will review the current Chinese legislation concerning the impact assessment of marine or coastal construction projects on underwater cultural heritage and explore the possibility for further improvement at the legislative level.

PB2219 EFFECTS OF SYSTEMIC MASTOCYTOSIS ON BONE HEALTH IN SOUTH‐EAST SCOTLAND

Background:Systemic mastocytosis (SM) is a rare condition characterised by excess mast cell production and often involves multiple organs. One organ system becoming increasingly recognised as being affected by systemic mastocytosis is the skeletal system, with reports of increased prevalence of osteoporosis, osteopenia and osteosclerosis represening the main findings.Aims:We aimed to assess the extent of bony involvement of SM in patients in our area, South‐East Scotland who had been referred to the Haematology services in NHS Lothian in order to help guide local policies regarding assessment of bone health upon a diagnosis of systemic mastocytosis.Methods:Clinical records of patients with a diagnosis of SM referred to our services in NHS Lothian available on our local TRAK system were interrogated to investigate for the presence of osteoporosis, osteopenia, osteosclerosis. Further, where available, DEXA bone scan results were tabulated.Results:We identified 18 patients with a diagnosis of SM with multiple variants identified including indolent (15/18), cutaneous, Aggressive with myelofibrosis (1/18) and SM with eosinophilia (1/18) and unclassified (1/18). It was found that 12/18 patients had evidence of osteoporosis (6/18), osteopenia (5/18) or osteosclerosis (1/18) representing a significant disease burden. Further, 13 of the 18 patients had a DEXA scan meaning there is a large portion of patients not being investigated routinely for bony involvement. The average age of patients with osteoporosis and SM was 60 years old with a range from 41 to 74, suggesting a profound effect on bone health at an early age.Summary/Conclusion:We have identified a significant proportion of patients with SM having bony involvement. It has been suggested that DEXA scans form part of initial workup of these patients upon diagnosis, with bisphosphonates used as a first line treatment. The findings of our study support the proactive investigation of bone health in SM.

Assessing the effectiveness of the EU AML regime: Detecting and investigating cases of trafficking in human beings

The effectiveness of anti-money-laundering (AML) mechanisms within the European Union (EU), in the context of the detection and investigation of trafficking in human beings (THB), is the focal point of this article. The article begins by examining the EU’s emphasis on proactive financial investigations in cases of THB and then moves on to examine EU AML framework. Special attention is paid to the 4th AML Directive (Directive (EU) 2015/849), the Second Transfer of Funds Regulation (Regulation (EU) 2015/847), the Second Payment Services Directive (Directive (EU) 2015/2366) and the Cash Control Regulation (Regulation (EC) 1889/2005). The modus operandi of traffickers operating within the EU when laundering the proceeds of their crimes is then studied, with the view of assessing the effectiveness of the framework. The analysis shows that the EU AML framework fails to capture some common modes of money laundering (ML) in THB cases and in addition, it is less effective when the criminal proceeds are laundered within the EU. The analysis furthermore shows that the EU AML regime is largely dependent on the ML risk assessment of private actors, many who do not comply with their AML obligations and are widely insufficiently monitored within the Member States (MS). The article concludes that the limitations of the EU AML framework and it’s enforcement in the MS have resulted in difficulties both in detecting ML associated with THB and in gathering evidence during THB investigations.

Matthew Bacon, Taking care of business. Police detectives, drug law enforcement and proactive investigation

Matthew Bacon, Taking care of business. Police detectives, drug law enforcement and proactive investigation

Dostęp do informacji publicznej jako prawne narzędzie zwalczania korupcji. (Glosa do wyroku Naczelnego Sądu Administracyjnego z dnia 3 stycznia 2012 r., sygn. akt: I OSK 2157/11)

This article is a voice of approval of the decision of the Supreme Administrative Court of 3 January 2012, Ref. Act: I OSK 2157/11. The ruling refers to the scope of public information that is available to the interested party. The court pointed out that public information could be invoices for services performed by private entities on behalf of public administrations. This ruling is part of anti-corruption strategies, based on transparency of the public life, and also supports the well-established case law, which treats public information very broadly. This results in an increase in the potential of the proactive investigation focused on cooperation with the community in the fight against corruption.

Les défis du droit pénal face à l’urgence sécuritaire

Following the attacks in January and November 2015, France passed laws specially turned to terrorism prevention, increasing the powers of judicial police and the prosecution, by the use of proactive investigations highly intrusive. New offenses relative to advocating terrorism revive the debate about the legitimacy of such offenses, including under the principal of legality of offenses and penalties.