Inclusion of Histopathology in Dose Range-Finding Nonclinical Studies for Inhaled Drug Products.

Drug development is a lengthy process that promotes and protects the health and safety of future patients. Nonclinical safety studies follow essentially similar designs that fulfill regulatory requirements but are amended based on factors including the mechanism of action, class of molecule, and route of administration. Clinical observations, clinical pathology, and macroscopic pathology in dose range-finding (DRF) studies generally provide sufficient information to select doses for pivotal studies by most delivery routes.

Precision Oncology and Systemic Targeted Therapy in Pseudomyxoma Peritonei.

Purpose: Pseudomyxoma peritonei (PMP) is a rare and poorly understood malignant condition characterized by the accumulation of intra-abdominal mucin produced from peritoneal metastases. Currently, cytoreductive surgery remains the mainstay of treatment but disease recurrence and death after relapse frequently occur in patients with PMP. New therapeutic strategies are therefore urgently needed for these patients.

A consulting room with a view: Psychotherapy and the ecological context.

Background: The field of psychotherapy is witnessing a lively debate today. The literature on the efficacy of psychological interventions has grown exponentially, but the assumptions of the prevailing research paradigms have been criticised from many points of view. One of the main concerns is that of a too often simplistic conception of psychotherapy, viewed as a set of specific methods for the treatment of point-like problems or symptoms.

Interpreting life-history traits, seasonal cycles, and coastal climate from an intertidal mussel species: Insights from 9000 years of synthesized stable isotope data.

Understanding past coastal variability is valuable for contextualizing modern changes in coastal settings, yet existing Holocene paleoceanographic records for the North American Pacific Coast commonly originate from offshore marine sediments and may not represent the dynamic coastal environment. A potential archive of eastern Pacific Coast environmental variability is the intertidal mussel species Mytilus californianus. Archaeologists have collected copious stable isotopic (δ18O and δ13C) data from M.

Rest-activity rhythm disruption and metabolic health in schizophrenia: a cross-sectional actigraphy study of community-dwelling people living with schizophrenia and nonpsychiatric comparison participants.

Study Objectives: People living with schizophrenia (PLWS) have increased physical comorbidities and premature mortality which may be linked to dysregulated rest-activity rhythms (RARs). This study aimed to compare RARs between PLWS and nonpsychiatric comparison participants (NCs) and to examine the relationships of RARs with age, sleep, metabolic, and physical health outcomes and, among PLWS, relationships of RARs with illness-related factors.

Methods: The study sample included 26 PLWS and 36 NCs, assessed with wrist-worn actigraphy to compute RAR variables and general sleep variables.